UI - 000149

AU - Abram SE

TI - 1992 Bonica Lecture. Advances in chronic pain management since gate control. [Review]

AB - OBJECTIVE. Two pain treatment systems that developed soon after the publication of the gate theory are probably a direct result of its publication: neuraxial opiate administration and electrical stimulation of the spinal cord and peripheral nerves and receptors. Although the use of these modalities has become widespread in managing chronic pain, there is disagreement about their long-term efficacy. This presentation will attempt to review the data regarding the mechanisms of action of these modalities and their efficacy in treating chronic pain of malignant and nonmalignant origin. DATA SOURCES. Data were derived almost entirely from original articles reporting experimental data from both animal and human studies and from series of patients undergoing treatment with the modalities reviewed. STUDY SELECTION. Where possible, controlled studies were selected. However, much of the available data regarding treatment results are uncontrolled. DATA EXTRACTION AND SYNTHESIS. Selected data from studies that were felt to be reasonably well conducted are presented or summarized. Because of the lack of control groups in many of the clinical trials, meta-analyses were not carried out. CONCLUSIONS. Long-term spinal opiate administration has been shown to be more effective than systemic opiates in some patients with cancer pain, but often must be combined with local anesthetics to provide satisfactory pain relief. Loss of effect over time is a significant problem. Since the identification of spinal opiate receptors and the introduction of spinally administered narcotics, a number of other receptors that are important in both sensitization and suppression of pain projection systems have been characterized. Agonists and antagonists to many of these receptors are being developed, and a few are available for clinical trials. Long-term electrical stimulation of the spinal cord produces substantial analgesia below the stimulated spinal segments in some patients with chronic pain. Although initial results are usually encouraging, long-term efficacy may be disappointing. It is postulated that analgesia associated with spinal stimulation is associated with both stimulation of large fiber ascending tracts and blockade of spinothalamic pathways. Transcutaneous electrical nerve stimulation (TENS) has come into widespread use in managing chronic pain and has had limited trials in cancer pain patients. It is well accepted by patients and physicians, but clinical studies of long-term efficacy have yielded variable results. The analgesic action is probably the result of both large afferent fiber activation and blockade of peripheral nociceptors. [References: 99]

SO - Regional Anesthesia 1993;18:66-8

UI - 000146

AU - Bushnell TG

AU - Justins DM

TI - Choosing the right analgesic. A guide to selection. [Review]

AB - Pain is an unpleasant sensory and emotional experience, unique to each individual patient. In the dynamic processes of nociceptive stimulation, signal transmission, central decoding and interpretation there are many potential sites for pharmacological intervention, and there are many drugs which will produce analgesia. An analgesic 'ladder' has been proposed for rational pain relief in cancer and a similar concept should be used in all forms of acute and chronic pain. Continuing research and drug development undoubtedly extends our understanding, but consistent improvement in our clinical ability to relieve pain depends more on our willingness to consider the need of each patient individually, to tailor the drug, route and mode of administration to that patient's requirements, and then to monitor on the basis of the response of the patient to the treatment. [References: 27]

SO - Drugs 1993;46:394-40

TI - Decision-making in the opioid therapy of cancer pain: interim analysis of a prospective survey

(Meeting abstract)

AB - Sequential trials of opioid drugs or routes of administration are frequently required to optimize the balance between analgesia and adverse effects. Neither the clinical factors that determine the choice of drug or route nor the variability in patient (pt) response have been studied previously. To assess these phenomena, we are evaluating pts referred to the Pain Service using a new instrument completed by the treating physician that records reason(s) for referral, pain-related data, and reason(s) for change(s) in analgesic regimen. To date, 25 consecutive pts with advanced cancer (11 males and 14 females; median age 51 yr, range 31-82) have been followed until discharge (n=23) or death (n=2). The reason(s) for referral included uncontrolled pain despite analgesic therapy (68%), difficulties in pain assessment (33%), and analgesic toxicity with inadequate (33%) or adequate (11%) analgesia. All pts had received previous opioid trials (median 3, range 1-6). Following referral, a total of 45 changes in either drug, route, or both were evaluable. Two pts died and 13 were discharged during the initial therapeutic trial. Ten required additional trials to achieve an acceptable balance between pain relief and adverse effects: 5 required 2 trials, 2 required 3 trials, and 3 required 4 or more sequential trials. The major factors that influenced opioid selection were previously well tolerated (48%), no known prior dose-limiting toxicity (51%), and easy to titrate (56%).

Convenience of formulations (24%) was associated only with the selection of morphine, whereas concerns regarding renal function (8%) and drug metabolites (14%) were associated with the selection of hydromorphone. The major reasons for the choice of a parenteral rather than oral route were the need for very rapid analgesic effect (66%), inability to swallow (31%), impaired intestinal function (25%) and intolerance of po administered drugs (18%). In the 2 cases in which spinal route was selected, dose- limiting toxicity with systemic administration was the compelling consideration. In 6 cases, an initial parenteral route was changed to the oral route prior to discharge; the need for rapid analgesic effect was a reason for the first selection, and resolution of that need and improved convenience were the reasons for the change. This interim analysis illustrates (1) the large variability in response to different opioids and routes of administration; (2) the potential utility of sequential therapeutic trials; and (3) the likely existence of trends in the rationale for the selection of opioid therapies, enhanced understanding of which may improve therapeutic decision making AD - Pain Service AD - Dept. of Neurology AD - Memorial Sloan-Kettering Cancer Center AD - New York AD - NY 10021 UI - 93695900

SO - Proc Annu Meet Am Soc Clin Oncol 1993;12:A1502-A150

UI - 000147

AU - Dixon BA

TI - Institutional survey of nurse anesthesia practice in patients receiving opioids via patient-

controlled analgesia

AB - This preliminary study determined certified registered nurse anesthetist (CRNA) practice experience and educational needs in the preoperative evaluation of patients using patient-controlled analgesia (PCA) for chronic and cancer pain management. A convenience sample (N = 29) of CRNAs practicing in a university teaching hospital completed the surveys developed by the investigator. Survey items related to CRNA experience with management of patients using PCA preoperatively, PCA modes of opioid delivery, and use of adjuvant medication for chronic and cancer pain patients. Results of the study indicated that 79% of CRNAs reported experience in administration of anesthesia to one or more patients who used PCA preoperatively. However, only 32% of CRNAs surveyed reported knowledge of the modes of opioid delivery available. Results also indicated that 48% of CRNAs were not familiar with adjuvant medications (ie, tricyclic antidepressants, benzodiazepines, steroids, and anticonvulsants), which are often prescribed in combination with opioids in chronic pain management. The respondents reported use of a variety of methods in handling opioid and infusion devices for patients using PCA preoperatively. Fifty-two percent of CRNAs disconnected the infusion and discarded the opioid preoperatively. Fourteen percent reported leaving the PCA device connected to the patient for use perioperatively or for continued pain management postoperatively. Based upon the findings of this preliminary study, CRNA education in management techniques for the use of PCA infusions in chronic and cancer pain is recommended

SO - Nurse Anesthesia 1993;4:112-11

TI - Flupirtine. A review of its pharmacological properties, and therapeutic efficacy in pain states. [Review]

AB - Flupirtine is a novel non-opiate centrally acting analgesic agent with muscle relaxant properties, advocated for use in a number of pain states. Preliminary evidence suggests that flupirtine 100 to 200mg orally or 150mg rectally 3 to 4 times daily (maximum daily dose 600mg) is more effective than placebo in relieving moderate acute pain of various types. For the relief of pain due to surgery, traumatic injury, dental procedures, headache/migraine and abdominal spasms, flupirtine has proved at least as effective as the opiate analgesics codeine, dihydrocodeine and pentazocine, the nonsteroidal anti-inflammatory agents suprofen, diclofenac and ketoprofen, as well as dipyrone and paracetamol (acetaminophen). Although evidence to support a role in the treatment of chronic pain is limited, flupirtine has been found as effective as pentazocine in short term trials of patients with muscular or neuralgiform pain, dysmenorrhoea, soft tissue rheumatism or cancer pain. The safety profile of flupirtine has not yet been fully established, although initial evidence suggests that adverse reactions, while frequent, are usually minor in nature. The most common reactions are drowsiness, dizziness, dry mouth and various gastrointestinal complaints. In comparison with opiate drugs, flupirtine appears to produce fewer central nervous system effects, no respiratory or cardiovascular depression, and no overt tolerance or physical dependence on prolonged administration. If these initially favourable results are confirmed in larger long term trials, then flupirtine would appear to represent an effective analgesic for the relief of moderate pain, particularly that of musculoskeletal origin.

[References: 75]

SO - Drugs 1993;45:548-56

AU - Goldman B

TI - Use and abuse of opioid analgesics in chronic pain. [Review]

AB - Primary care physicians are frequently required to treat patients with chronic debilitating pain. Opioid analgesics can successfully manage chronic pain. To prescribe opioid analgesics effectively, physicians must identify appropriate patients. Several methods can be used to identify and distinguish appropriate patients, addicted patients, and for-profit drug seekers. [References: 15]

SO - Canadian Family Physician 1993;39:571-57

AU - Helme RD

AU - Katz B

TI - Management of chronic pain. [Review]

AB - The principles of chronic pain management in the elderly are the same as in younger people; whenever possible, the cause of the pain should be identified and eradicated. However, older people are more likely to suffer pain from incurable conditions, and the emotional component of the suffering may be considerable. Treatment options include analgesics, opiates, antidepressants and anticonvulsants as well as psychological strategies, physical strategies such as exercise and transcutaneous electrical nerve stimulation (TENS), and surgery. Improvement of function may be a more important treatment goal than relief of pain.

[References: 15]

SO - Medical Journal of Australia 1993;158:478-48

AU - Kerrick JM

AU - Fine PG

AU - Lipman AG

AU - Love G

TI - Low-dose amitriptyline as an adjunct to opioids for postoperative orthopedic pain: A placebo-controlled trial

AB - IN: U Minnesota Coll of Pharmacy, Minneapolis, US LA: English AB: Investigated the usefulness of a tricyclic antidepressant in the management of chronic pain. 28 patients (aged 38-79 yrs) undergoing surgery completed a randomized, placebo-controlled, double-blinded trial of 50 mg of amitriptyline (AMT) po HS on postoperative days 1, 2, and 3 while using patient-controlled morphine or meperidine analgesia. Visual analog and numerical verbal pain ratings, sedation scores, sleep quantity/quality scores, and sense of well-being scores were assessed twice daily on each of the days succeeding AMT/placebo use. AMT was no different than placebo in altering the majority of postoperative symptom variables studied in the sample study population but caused no significant adverse effects. There does not appear to be an opioid-sparing effect nor an improvement in general well-being. Results of this study do not support general use of AMT as a coanalgesic. (PsycLIT Database Copyright 1993 American Psychological Assn, all rights reserved) KP: adjunctive low dose amitriptyline with patient controlled morphine or meperidine analgesia; 38-79 yr olds with postoperative orthopedic chronic pain AN: 80-34733

SO - Pain 1993;52:325-33

AU - Kong H

AU - Raynor K

AU - Yasuda K

AU - Moe ST

AU - Portoghese PS

AU - Bell GI

AU - Reisine T

TI - A single residue, aspartic acid 95, in the delta opioid receptor specifies selective high affinity agonist binding

AB - The enkephalins, dynorphins, and endorphins are endogenous opioids which function as neurotransmitters, neuromodulators, and hormones and are involved in the perception of pain, modulation of behavior, and regulation of autonomic and neuroendocrine function. Pharmacological studies have defined three classes of opioid receptors, designated as delta, kappa, and mu. To investigate mechanisms by which agonists and antagonists interact with the delta opioid receptor, we have substituted aspartic acid 95 in the transmembrane segment 2 of the cloned mouse delta opioid receptor with an asparagine (D95N). The D95N mutant receptor had reduced affinity for delta receptor-selective agonists such as enkephalin, [D-Pen2,D-Pen5]enkephalin and [D-Ser2,Leu5]enkephalin-Thr6 such that it did not bind these peptides even at micromolar concentrations. The binding of delta-selective non-peptide agonists was also reduced. In contrast, the delta receptor-selective antagonists, such as naltrindole, the benzofuran analog of naltrindole, and 7-benyllidenenaltrexone, bound equally well to the wild-type and mutant receptor. Similarly, non-

selective opioid agonists such as bremazocine and buprenorphine, which interact with delta, kappa, and mu

opioid receptors, showed no difference in binding to the wild-type and mutant delta receptor. The D95N

mutant remained coupled to G proteins, and the receptor was functionally active since it mediated agonist

inhibition of cAMP accumulation. These results indicate that selective agonists and antagonists bind

differently to the delta receptor and show that Asp-95 contributes to high affinity delta-selective agonist

binding. The identification of a key residue involved in selective agonist binding to the delta opioid receptor

will facilitate the development of novel therapeutic reagents that can be used for the treatment of chronic

pain and other conditions.

SO - Journal of Biological Chemistry 1993;268:23055-2305

UI - 000150

AU - Krames ES

TI - Intrathecal infusional therapies for intractable pain: patient management guidelines

AB - This article focuses on appropriate patient selection for and management of patients selected for

continuous spinal infusional opioid therapy. Patients with cancer-related pain who have undergone sequential

strong opioid drug trials, who have intractable, unmanageable side effects, and who have undergone a

successful spinal opioid efficacy trial are candidates for implantable spinal infusional therapy. Patients with

noncancer-related chronic pain, who have failed all conventional syndrome-specific therapies before

neuroablative surgical procedures, including sequential strong opioid drug trials, who have

intractable, unmanageable side effects, and who have undergone successful spinal opioid efficacy trial

are deemed candidates for implantable spinal infusional therapy. Patients with chronic noncancer-

related pain and patient with cancer-related pain who have life expectancies greater than 3 mo all have

implanted programmable infusion pumps. Patients with cancer-related pain who have life expectancies less

than 3 mo have implanted permanent epidural catheters connected to external pump systems. Management

guidelines for complications of therapy broadly categorized as surgical, mechanical, and pharmacologic are


SO - Journal of Pain & Symptom Management 1993;8:36-4

UI - 000151

AU - Lipchik GL

AU - Milles K

AU - Covington EC

TI - The effects of multidisciplinary pain management treatment on locus of control and pain beliefs

in chronic non-terminal pain

AB - OBJECTIVE: To determine whether chronic pain patients' beliefs and attributions about pain control

are amenable to change in a short-term inpatient multidisciplinary pain management program. DESIGN:

Non-randomized consecutive sample with prospective, before-after treatment. SETTING: Pain-

management, tertiary care center in a major U.S. city. PATIENTS: All adult patients (n = 50) who were

treated in an inpatient multidisciplinary pain management center were contrasted with those of a control

group of 46 adult patients who were treated in an outpatient pain center. OUTCOME MEASURES: Pain

Locus of Control Scale, the Pain Beliefs and Perceptions Inventory, subjective pain intensity, and medication

usage were measured before and after treatment. RESULTS: Statistically significant posttreatment changes

were found for the treatment group, but not the control group. Patients who completed the inpatient pain

management program reported significant decreases in subjective pain intensity despite discontinuation of

narcotic analgesics. Patients in the treatment group showed an increased sense of personal control over their

pain and substantial decreases in attributions of pain control to powerful others and chance. Patients in the

treatment group also showed a significant reduction in their endorsement of the belief that their pain was a

mysterious phenomenon. CONCLUSIONS: Chronic non-terminal pain patients' beliefs about pain and

attributions of pain control are amenable to change in a short-term inpatient multidisciplinary pain

management program. These results suggest that an intensive multidisciplinary program involving

psychotherapy might be more effective in treating chronic pain patients similar to those in this study than

outpatient treatment without psychotherapy.

SO - Clinical Journal of Pain 1993;9:49-5

UI - 000206

AU - Portenoy RK

TI - Therapeutic use of opioids: prescribing and control issues

AB - AB - [No Abstract Available] AD - Department of Neurology AD -Memorial Sloan-Kettering Cancer

Center AD - New York 10021 UI -94019720

SO - NIDA Res Monogr 1993;131:35-5

UI - 000254

AU - Weissman DE

TI - Doctors, opioids, and the law: the effect of controlled substances regulations on cancer pain


AB - AB - Opioids are underused by physicians for the treatment of cancer pain. Reasons for this include

excessive concern about opioid-induced respiratory depression, tolerance, and addiction, as well as the

impact of controlled substances regulations. The negative impact of controlled substances regulations on

patient care is not well understood. This paper reviews the historical basis and current structure of the

regulatory system. Four potential ways in which controlled substances regulations and policies can affect

medical care are discussed: (1) by placing restrictions on physician practice, (2) by affecting patient access to

opioids, (3) by stigmatizing patients, and (4) indirectly through physicians' perceptions of regulations,

resulting in modified medical practices. Physicians are urged to work with state regulatory agencies to

identify regulatory impediments to appropriate patient care. AD - Division of Cancer and Blood Diseases

AD - Medical College of Wisconsin AD -Milwaukee UI - 93235094

SO - Semin Oncol 1993;20:53-5

UI - 000154

AU - Wilder-Smith CH

TI - [Non-opioids in pain therapy: current perspectives]. [German]

AB - Increasing knowledge of the mechanisms underlying nociceptive processing are making a more

rationale approach to pain treatment possible. Recent research has confirmed relevant differences between

NSAIDs and the direct analgesic action of several psychotropic drugs. Alpha 2-adrenergic agonists are being

clinically tested and have shown considerable analgesic activity in various pain states. Simultaneous

treatment of pain with complementary analgesics, i.e. "balanced analgesia", seems to be a logical approach in

the light of the close interactions between the different nociceptive pathways. The indications for the use of

known analgesics in chronic pain therapy are insufficiently researched.

SO - Schweizerische Rundschau fur Medizin Praxis 1993;82:271-27

UI - 000172

AU - Zenz M

AU - Willweber-Strumpf A

TI - Opiophobia and cancer pain in Europe [see comments]

SO - Lancet 1993;341:1075-107

UI - 000155

AU - Beltrutti DP

AU - Ardizzone A

AU - Parola P

TI - Continuous spinal analgesia by means of micropumps[correction of micropumpus]: a report of

163 chronic pain patients

AB - Chronic pain in patients suffering from advanced cancer as well as unbearable chronic pain states

depending on non-malignant pathology have always represented a test bench to verify results of advanced

therapeutical programs as to more traditional approaches. The Authors present their experience resulting

from longterm spinal infusion with peridural catheters connected to portable micropumps for the continuous

administration of analgesic solutions. The availability of portable micropumps, a better understanding of

spinal opioid receptors and advances in pharmacokinetics of opiate analgesics led in these years to a

tremendous improvement of pain control possibilities and of the quality of life of patients.

SO - Panminerva Medica 1992;34:128-13

UI - 000194

AU - Brescia FJ

AU - Portenoy RK

AU - Ryan M

AU - Krasnoff L

AU - Gray G

TI - Pain, opioid use, and survival in hospitalized patients with advanced cancer

AB - AB - PURPOSE: Pain is a common and feared symptom for patients with incurable cancer.

Comprehensive assessment provides the foundation for effective pain management, and data that clarify the

relationship between pain and other relevant factors also facilitate this process. The main objective of the

study was to develop a clinical data base for advanced cancer patients and to survey data to determine (1)

pain severity at admission, (2) opioid use at admission, (3) change in opioid use during the hospital stay, and

(4) survival in the hospital. PATIENTS AND METHODS: Information was collected prospectively on

1,103 patients admitted and on 1,017 patients who died within 6 months of the study's end. Demographic

and clinical data were recorded 72 hours after admission and soon after death or discharge. RESULTS:

Seventy-three percent of patients had pain at admission. Cancer of the cervix was frequently (68%)

associated with severe pain, as were prostate (52%) and rectal/sigmoid tumors (49%). Severe pain was more

probable in those with bone metastasis, those admitted from home, and in those younger than 55 years of

age. The majority (71.7%) of patients had a stable dosing pattern, and only 4.2% of the patients required

dose increases of at least 10% per day. CONCLUSION: This study demonstrated the wide variability in

opioid doses required. No reliable predictor of opioid requirement was identified, and this lack of

predictability of cancer pain severity underscores the need for ongoing assessment. AD - Calvary Hospital

AD - Bronx AD - NY 10461 UI - 92092056

SO - J Clin Oncol 1992;10:149-15

UI - 000211

AU - Cherny NI

AU - Thaler HT

AU - Friedlander-Klar H

AU - Lapin J

AU - Portenoy RK



AB - AB - Neuropathic pain resulting from damage to the central or peripheral nervous system is common

in cancer patients (pts). Controversy exists about the opioid responsiveness of this type of pain. Some

clinicians have suggested that these pains may be inherently resistant to opioid analgesia; others have

postulated that the neuropathic mechanism may relatively diminish the analgesic response. To assess these

hypotheses, we performed a combined analysis of the results from 4 controlled single-dose analgesic trials

performed from 1978 to 1982, with morphine or heroin at high and low doses. Analgesic response was

assessed serially over a 6-hr interval using a visual analog scale and was summarized as a total pain relief

(TOTPAR) score. A total of 194 pts with chronic cancer pain were included; there were 482 administrations

of study drug. Median age was 52 yr (20-79). Information about characteristics of pts' pain recorded at the

time of study was reviewed independently by 2 experienced pain clinicians who grouped each case according

to inferred pain mechanism (neuropathic, nociceptive or mixed) and the degree of confidence in the inferred

mechanism (definite vs probable/possible). When initial groupings differed, they were rereviewed with a

third investigator and disagreement was resolved by consensus. Cases were grouped as follows: nociceptive

pain only (n=210), neuropathic pain only (n=51) and mixed (n=221). Analgesic responsiveness was

evaluated comparing TOTPAR scores using the Student's t-test. TOTPAR for the entire group was not

predicted by the specific drug (morphine vs heroin), but the dose (high vs low) was a significant predictor of

TOTPAR. Placebo TOTPAR response was estimated at 5.1, significantly less than the mean observed with

any group. The primary analysis for the study compared analgesic response of pts having any neuropathic

component with those with only nociceptive pain. Results are presented in a table. In a covariate analysis

that adjusted for prior opioid exposure and other prognostic factors, the opioid responsiveness of

neuropathic pain was significant and was less than that of purely nociceptive pain. These data support the

postulate that opioid responsiveness is a continuum and that it is diminished by the neuropathic mechanism

AD - Pain Service AD - Dept. of Neurology AD - Memorial Sloan-Kettering Cancer Center AD - New

York AD - NY 10021 UI - 92682059

SO - Proc Annu Meet Am Soc Clin Oncol 1992;11:A1330-A133

UI - 000188

AU - Culpepper-Morgan JA

AU - Inturrisi CE

AU - Portenoy RK

AU - Foley K

AU - Houde RW

AU - Marsh F

AU - Kreek MJ

TI - Treatment of opioid-induced constipation with oral naloxone: a pilot study

AB - Opioids cause constipation by binding to specific opioid receptors in the enteric and central nervous

systems. First-pass glucuronidation limits systemic bioavailability of oral naloxone. This study was designed

to determine if oral naloxone could reverse opioid-induced constipation without precipitating abstinence or

recrudescence of pain in opioid-dependent individuals. Concentrations of unmetabolized and total naloxone,

including naloxone glucuronide, were measured by radioimmunoassay. A dose-related increase in symptoms

of laxation resulted in all three opioid-dependent patients studied that paralleled the increase in active and

total naloxone plasma levels. Withdrawal symptoms occurred with plasma naloxone area under the plasma

concentration-time curves above 550 ng.min/ml and with dosing intervals less than 3 hours. Peak plasma

levels did not predict withdrawal. Oral naloxone ameliorates opioid-induced constipation in opioid-

dependent persons. Titration of dose to a maximum of 12 mg at least 6 hours apart may be needed to avoid

adverse reactions.

SO - Clin Pharmacol Ther 1992;52:90-9

UI - 000164

AU - Dimski DS

AU - Hebert LA

AU - Sedmak D

AU - Ogrodowski JL

AU - Elkhammas EA

AU - Tesi RJ

AU - Gold M

AU - Courville CS

TI - Renal autotransplantation in the loin pain-hematuria syndrome: a cautionary note

AB - The current literature suggests that renal autotransplantation is nearly uniformly effective in

controlling the severe and debilitating pain of the loin pain-hematuria syndrome (LPHS). However, we

report two patients thought to have this syndrome in whom renal autotransplantation did not result in long-

term control of pain. In case 1, autotransplantation resulted in immediate cessation of pain; however, the

flank pain recurred 7 1/2 months later. The recurrent pain was also severe and debilitating, requiring narcotic

medications for control. In case 2, autotransplantation of the left kidney resulted in chronic pain in the left

pelvic area, the site of the autotransplanted kidney. In addition, the patient continued to experience chronic

discomfort in the left flank and along the flank incision. One year after autotransplantation, the patient still

requires multiple daily doses of narcotic medications for pain control. Our two patients represent the 13th

and 14th reported patients subjected to renal autotransplantation for management of LPHS. They represent

only the third and fourth reported patients with recurrence of pain after renal autotransplantation. Because

studies with negative results are less likely to be reported in the literature than studies with positive results, it

is possible that the literature overestimates the effectiveness of renal autotransplantation in the LPHS. To

assess the true effectiveness of renal autotransplantation in LPHS, a survey of patients with LPHS who have

undergone renal autotransplantation needs to be performed.

SO - American Journal of Kidney Diseases 1992;20:180-18

UI - 000016

AU - Eisele JH

AU - Grigsby EJ

AU - Dea G

TI - Clonazepam treatment of myoclonic contractions associated with high-dose opioids: Case report

AB - IN: U California-Davis, Sacramento, US LA: English AB: Presents the case of a 30-yr-old man with

chronic abdominal pain who was treated with high doses of iv hydromorphone and developed severe and

frequent myoclonic contractions. Several medications including lorazepam failed to control the contractions;

however, clonazepam in normal doses reduced the myoclonus dramatically. (PsycLIT Database Copyright

1992 American Psychological Assn, all rights reserved) KP: clonazepam; hydromorphone induced myoclonic

contractions; 30 yr old male with chronic abdominal pain; case report AN: 79-44237

SO - Pain 1992;49:231-23

UI - 000161

AU - Fishbain DA

AU - Rosomoff HL

AU - Rosomoff RS

TI - Detoxification of nonopiate drugs in the chronic pain setting and clonidine opiate detoxification.


AB - Although the pain physician is most familiar with the treatment of the opiate withdrawal syndrome,

other drugs are abused by the chronic pain patient. The pain physician should then be familiar with the

withdrawal syndromes associated with other drug groups. The withdrawal syndromes associated with

hypnosedatives, psychotomimetics, nicotine, stimulants, ergot alkaloids, beta adrenergic blocking agents,

antidepressants, muscle relaxants, and alpha-adrenergic agonists are described. Drug detoxification protocols

for these drugs are reviewed. Additionally, the rationale for clonidine opiate detoxification is discussed, and

current clonidine detoxification protocols are reviewed. [References: 89]

SO - Clinical Journal of Pain 1992;8:191-20

UI - 000207

AU - Galer BS

AU - Coyle N

AU - Pasternak GW

AU - Portenoy RK

TI - Individual variability in the response to different opioids: report of five cases

AB - AB - Although it is widely appreciated that patients can demonstrate highly variable responses to

different opioid drugs, there have been few detailed descriptions of this phenomenon. To illustrate this

variability, we present 5 patients, 4 with cancer pain and 1 with non- malignant pain, who underwent dose

titration with more than 1 opioid and developed markedly different responses to each. In every case, dose

escalation led to successful treatment with 1 opioid and to intolerable side effects without adequate relief

with others. The existence of this individual variability in the response to different opioids has important

implications for both clinical practice and current understanding of opioid pharmacology in man. It

contradicts the view that any opioid is inherently more efficacious than any other, suggests that patients who

fail to obtain adequate pain relief at maximally tolerated doses of 1 opioid may benefit from an alternative

drug, and underscores the potential importance of genetic factors as a determinant of opioid response. AD -

Department of Neurology AD - Memorial Sloan-Kettering Cancer Center AD - New York AD - NY 10021

UI - 92278827

SO - Pain 1992;49:87-9

UI - 000019

AU - Hamilton J

AU - Edgar L

TI - A survey examining nurses' knowledge of pain control

AB - IN: Victoria General Hosp, Halifax, NS, Canada LA: English AB: Surveyed 318 nurses at an acute

care teaching hospital to identify their knowledge of pain assessment and management. Two pain

instruments by M. McCaffery et al (1990) were combined and adapted for use. The final instrument, the Pain

Control Survey, was administered to Ss. Ss lacked knowledge and understanding of opioid addiction,

equivalent dosing, properties of opioids, and differences in acute and chronic pain. No significant differences

were found in the scores by level of educational preparation or by years of experience. Presentation of the

results unit by unit demonstrated that the instrument was suitable as an educational tool as well as an

effective strategy to introduce Ss to nursing research. (PsycLIT Database Copyright 1992 American

Psychological Assn, all rights reserved) KP: knowledge of pain assessment & management with narcotic

opioid analgesics; nurses at acute care teaching hospital AN: 79-29038

SO - Journal of Pain and Symptom Management 1992;7:18-2

UI - 000165

AU - Litman RS

AU - Shapiro BS

TI - Oral patient-controlled analgesia in adolescents

AB - Adolescence is a time when concerns about independence and self-control are of paramount

importance. These developmental issues must be considered when planning treatment for adolescents with

acute or chronic pain. Patient-controlled analgesia (PCA) is a method of administering opioids that

reinforces patient autonomy. Traditionally, opioids given by PCA are administered via the intravenous or

subcutaneous route. Issues of autonomy and control, however, are no less important for patients receiving

oral opioids. To augment patient autonomy, we have provided oral medication kept at the bedside (oral

bedside PCA) for adolescents with diverse pain problems. We describe our selection criteria and methods for

using oral bedside PCA with adolescents and present 4 patients who used this method.

SO - Journal of Pain & Symptom Management 1992;7:78-8

UI - 000162

AU - McQuay HJ

AU - Jadad AR

AU - Carroll D

AU - Faura C

AU - Glynn CJ

AU - Moore RA

AU - Liu Y

TI - Opioid sensitivity of chronic pain: a patient-controlled analgesia method

AB - Twenty-two patients with chronic pain of malignant or nonmalignant origin were given intravenous

morphine by patient-controlled analgesia. A prestudy judgment was made from the characteristics of the pain

as to whether it was nociceptive or neuropathic. Analgesic efficacy was assessed by a nurse-observer;

adverse events were noted and plasma morphine and metabolitie concentrations measured. Three categories

of opioid response were distinguished. Good responders obtained > 70 mm relief on the visual analogue

scale, with minimal or manageable adverse events. Moderate responders obtained < 70 but > 30 mm relief

with more problematic adverse events, and poor responders had < 30 mm relief with troublesome adverse

events. This method for the study of opioid sensitivity allowed a wide dosage range to be studied. The

simultaneous analgesic and adverse event measurements showed that the spectrum of observed response was

wide, and response category could be judged for the majority by 4 h. In those with poor or moderate

response, adverse event severity limited further dose increment. The relationship between pain

characteristics and response showed that some pains judged to be neuropathic had a good response to opioid

(5/13), and some pains judged to be nociceptive did not (5/14). The study suggests that the pattern of

response is not as black and white as the prediction of good response from nociceptive pain and poor from

neuropathic pain would suggest, although nociceptive pain was more likely than neuropathic pain to show a

good response. For the moderate responders opioid titration may, in the absence of other effective

treatments, be useful, but the analgesic endpoint may not be totally satisfactory. The method provides an

operational definition of opioid sensitivity.

SO - Anaesthesia 1992;47:757-76

UI - 000169

AU - Moulin DE

AU - Johnson NG

AU - Murray-Parsons N

AU - Geoghegan MF

AU - Goodwin VA

AU - Chester MA

TI - Subcutaneous narcotic infusions for cancer pain: treatment outcome and guidelines for use [see


AB - OBJECTIVE: To provide guidelines for the institution and maintenance of a continuous subcutaneous

narcotic infusion program for cancer patients with chronic pain through an analysis of the narcotic

requirements and treatment outcomes of patients who underwent such therapy and a comparison of the costs

of two commonly used infusion systems. DESIGN: Retrospective study. SETTING: Tertiary care facilities

and patients' homes. PATIENTS: Of 481 patients seen in consultation for cancer pain between July 1987

and April 1990, 60 (12%) met the eligibility criteria (i.e., standard medical management had failed, and they

had adequate supervision at home). INTERVENTION: Continuous subcutaneous infusion with

hydromorphone hydrochloride or morphine started on an inpatient basis and continued at home whenever

possible. OUTCOME MEASURES: Patient selectivity, narcotic dosing requirements, discharge rate, patient

preference for analgesic regimen, side effects, complications and cost-effectiveness. RESULTS: The mean

initial maintenance infusion dose after dose titration was almost three times higher than the dose required

before infusion (hydromorphone or equivalent 6.2 v. 2.1 mg/h). Eighteen patients died, and the remaining 42

were discharged home for a mean of 94.4 (standard deviation 128.3) days (extremes 12 and 741 days). The

mean maximum infusion rate was 24.1 mg/h (extremes 0.5 and 180 mg/h). All but one of the patients

preferred the infusion system to their previous oral analgesic regimen. Despite major dose escalations nausea

and vomiting were well controlled in all cases. Twelve patients (20%) experienced serious systemic toxic

effects or complications; six became encephalopathic, which necessitated dose reduction, five had a

subcutaneous infection necessitating antibiotic treatment, and one had respiratory depression. The


computerized infusion pump was found to be more cost-effective than the disposable infusion device after a

break-even point of 8 months. CONCLUSIONS: Continuous subcutaneous infusion of opioid drugs with the

use of a portable programmable pump is safe and effective in selected patients who have failed to respond to

standard medical treatment of their cancer pain. Dose titration may require rapid dose escalation, but this is

usually well tolerated. For most communities embarking on such a program a programmable infusion system

will be more cost-effective than a disposable system

SO - Canadian Medical Association Journal 1992;146:891-89

UI - 000015

AU - Ollat H

TI - Traitement pharmacologique de la douleur neuropathique. / Pharmacological treatment of

neuropathic pain

AB - IN: Association pour la Neuro-Psycho-Pharmacologie, Paris, France LA: French AB: Reviews the

recent literature on pharmacological treatment of neuropathic pain (i.e., chronic pain resulting from injury to

the peripheral nervous system and induced by functional changes in peripheral and central pathways). Drugs

currently prescribed for neuropathic pain are discussed in terms of their effectiveness, indications, and

mechanisms of action. Data are presented on the use of various antidepressants, opiates, and anticonvulsants

for different neuropathic pain syndromes (e.g., trigeminal neuralgia, diabetic neuropathy, and postherpetic

neuralgia). Preliminary data from new pharmacological approaches (e.g., capsaicin, local anesthetics, and

anti-inflammatory agents) are reviewed, and research recommendations are provided. (English abstract)

(PsycLIT Database Copyright 1993 American Psychological Assn, all rights reserved) KP: pharmacological

treatment & drug indications & mechanisms of action; chronic neuropathic pain resulting from peripheral

nervous system injury; research review AN: 30-86136

SO - Revue Neurologique 1992;148:521-53

UI - 000156

AU - Osipova NA

AU - Petrova VV

AU - Novikov GA

AU - Beresnev VA

AU - Sergeeva IE

AU - Dolgopolova TV

TI - [Norfin in oncological practice]. [Russian]

AB - A synthetic opiate agonist-antagonist norphin (buprenorphin) has been studied in 297 cancer patients

as an analgetic component of general anesthesia, in postoperative analgesia and in the treatment of chronic

pain syndrome. In modified neuroleptanalgesia based on norphin, diazepam, droperidol and N2O the patient

is more adequately prevented from surgical trauma than in conventional neuroleptanalgesia based on

fentanyl. This is confirmed by greater stability in circulation, metabolism and stress

hormone parameters, however this anesthesia technique is less manageable and may be accompanied by

prolonged postanesthesia depression of the central nervous system. Good results have been obtained when

norphin pills were used sublingually for the treatment of long-lasting intensive chronic pain syndrome in

incurable cancer patients. Norphin is no less effective than morphin, however, unlike morphin, it causes no

severe adverse reactions.

SO - Anesteziologiya i Reanimatologiya 1992;:3-

UI - 000163

AU - Patterson KL

TI - Pain in the pediatric oncology patient

AB - Pediatric oncology nurses face many challenges in treating the pain associated with childhood cancer.

The type and severity of pain children with cancer experience varies from acute, short-term, procedure-

related pain to the progressive chronic pain associated with terminal illness. In addition, the unfounded fears

of using strong narcotic analgesics and the underutilization of psychological techniques to treat pain in

children limit the effectiveness of pain management. Armed with objective data, pediatric oncology nurses

can work with other members of the cancer treatment team to provide relief from the pain associated with

the diagnosis and treatment of childhood cancer.

SO - Journal of Pediatric Oncology Nursing 1992;9:119-13

UI - 000157

AU - Rothman RB

TI - A review of the role of anti-opioid peptides in morphine tolerance and dependence. [Review]

AB - Studies on the mechanisms of tolerance and dependence have mostly focused on changes at the

receptor level. These experiments, conducted with model systems ranging from clonal cell lines to whole

animals, have identified a number of important adaptive

mechanisms which occur at the receptor level. However, none of these adaptive mechanisms can completely

account for the phenomena which serve to define the state of morphine tolerance and dependence, especially

the observation that as an animal becomes more tolerant to morphine, less naloxone is required to trigger

withdrawal. The data reviewed in this paper provide strong support for the hypothesis that the brain

synthesizes and secretes neuropeptides which act as part of a homeostatic system to attenuate the effects of

morphine and endogenous opioid peptides. According to this model, administration of morphine releases

anti-opioid peptides (AOP), which then attenuate the effects of morphine. As more morphine is given, more

AOP are released, thereby producing tolerance to the effects of morphine. Cessation of morphine

administration, or administration of naloxone, produces a relative excess of anti-opioid, which is in part

responsible for the withdrawal syndrome. Since endogenous and exogenous antagonists might together

produce synergistic effects, less naloxone might be required to trigger withdrawal in the presence of higher

levels of AOPs. Although the study of AOP is in its infancy, a deeper understanding of the central nervous

system (CNS) anti-opioid systems may lead to new treatments for chronic pain, substance abuse, and

psychiatric disorders. [References: 114]

SO - Synapse 1992;12:129-13

UI - 000168

AU - Sagen J

TI - Chromaffin cell transplants for alleviation of chronic pain

AB - Treatment of intractable pain with parenteral, subarachnoid, or epidural narcotics is often

unsatisfactory due to tolerance and other systemic complications that accompany increasing dosages of these

drugs. Other disadvantages include the potential infections with implantable pumps and the inconvenience of

repeated narcotic administration. During the past several years, studies at the author's laboratory indicated

that transplantation of adrenal medullary tissue or isolated chromaffin cells into the spinal subarachnoid

space can significantly reduce pain in several rodent models without resulting in development of tolerance.

Adrenal medullary chromaffin cells were selected because they produce high levels of both opioid peptides

and catecholamines, agents that independently, and possibly synergistically, reduce pain when injected locally

into the spinal subarachnoid space. The adrenal medullary transplants survive for prolonged periods, and

continue to produce high levels of both catecholamines and met-enkephalin. These transplants reduce pain in

two rodent chronic pain models, an arthritis model and a peripheral neuropathy model, both of which closely

resemble human chronic pain syndromes. The success of the animal studies has led to initiation of human

clinical trials in patients with chronic cancer pain; results are promising.

SO - ASAIO Journal 1992;38:24-2

UI - 000166

AU - Smythe M

TI - Patient-controlled analgesia: a review. [Review]

AB - The patient-activated analgesic system was introduced in 1968. Early trials, although uncontrolled,

supported the safety and efficacy of patient-controlled analgesia (PCA) in several kinds of pain, such as that

relating to surgery, cancer, trauma, and obstetric procedures. In the past decade, prospective, randomized

trials have reported several advantages of PCA over conventional analgesia in the early postoperative period.

Although not supported by all controlled trials, they include improved pain relief, less sedation, lower level

of narcotic consumption, fewer postoperative complications, greater patient satisfaction, and improved

pulmonary function. Preliminary results in the management of chronic pain indicate that PCA can lead to

significant lifestyle improvements in ambulatory patients with cancer. The most significant, although

infrequent, adverse effect is respiratory depression, the majority of cases occurring in patients predisposed

secondary to concomitant illness or as a result of human error. The clinical use of PCA will likely see a

significant increase among persons with cancer, and an increase in epidural administration. The cost benefit

of PCA has yet to be assessed in inpatient and outpatient settings. [References: 114]

SO - Pharmacotherapy 1992;12:132-14

UI - 000159

AU - Sorensen HT

AU - Rasmussen HH

AU - Moller-Petersen JF

AU - Ejlersen E

AU - Hamburger H

AU - Olesen F

TI - Epidemiology of pain requiring strong analgesics outside hospital in a geographically defined

population in Denmark

AB - Based on obligatory notifications from pharmacies to the National Board of Health about prescription

of strong analgesics as well as questionnaires to the prescribing doctors, the occurrence and causes of pain

requiring strong analgesics outside hospitals were analysed over a period of one month in Denmark in a

limited population (480,000), corresponding to nearly 10% of the Danish population. During one month,

strong analgesics were prescribed to 0.2 per cent of the population. The commonest acute conditions were

back pain (23%) and trauma (17%). The commonest recurrent acute conditions were headache (25%) and

angina pectoris (17%). The commonest chronic non-malignant conditions were back pain (29%) and

pancreatitis (7%). The commonest malignant conditions were lung cancer (20%) and colorectal cancer

(14%). The commonest conditions indicated under the chronic pain syndrome were headache (33%) and

back pain (13%). Conditions requiring strong analgesics reflect to some extent the distribution of painful

conditions in the general population.

SO - Danish Medical Bulletin 1992;39:464-46

UI - 000160

AU - Terman GW

AU - Loeser JD

TI - A case of opiate-insensitive pain: malignant treatment of benign pain

AB - OBJECTIVE: We report the case of a woman with presumed cancer pain treated with escalating

doses of opiates despite no evident improvement in her pain and several deleterious side effects. PATIENT:

A 62-year-old woman with cervical myelopathy and a diagnosis of a spinal cord tumor was referred to the

University of Washington Medical Center complaining of chest tightness, multiple joint pains, nausea,

constipation, seizures and a deteriorating memory. At the time of admission she was confined to her bed

with a full-time attendant and was receiving 240 milligrams of intravenous morphine per hour for her pain.

INTERVENTION: Diagnostic studies failed to find any evidence of neoplasm and revealed only an old

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Subject: Re: Pain Medication #1

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hemorrhage within the cervical spinal cord. A program of increasing physical and occupational therapy and

decreasing opiate intake was initiated. RESULTS: Within a month the patient's pain complaints decreased,

as did the rest of her presenting complaints. Her activities of daily living greatly increased making attendant

care no longer necessary. CONCLUSIONS: This case report illustrates some of the hazards of opioid

therapy in the management of patients with chronic pain. Our patient's opiate therapy was expensive, gave

her undesirable side effects, and did not reduce her pain complaints or improve her function. In the treatment

of chronic pain, of noncancerous or cancerous origin, a) systemic opioids may not be effective in reducing

pain complaints in every patient, b) treatment efficacy evaluation should always include functional endpoints,

and c) nonefficacious treatments should not be continued indefinitely

SO - Clinical Journal of Pain 1992;8:255-25

UI - 000167

AU - Tobias JD

AU - Oakes L

AU - Austin BA

TI - Pediatric analgesia with epidural fentanyl citrate administered by nursing staff

AB - Even though epidural analgesia is effective and has advantages over conventional postoperative

analgesia, it is also labor intensive, requiring 24-hour supervision by an anesthesiologist. In an effort to

decrease the manpower requirements, some hospitals allow the nursing staff to administer epidural narcotics

to adult patients. In children, however, this practice has been limited. We retrospectively reviewed our

experience over 12 months with this procedure. Epidural catheters (caudal, lumbar, or thoracic) were placed

in 43 pediatric patients for acute and chronic pain management. All patients received a continuous epidural

infusion of bupivacaine hydrochloride with fentanyl citrate. Eleven (26%) of the 43 patients required

supplemental analgesia and were given 45 doses of epidural fentanyl. Adequate analgesia was achieved in all

patients. No intravascular or intrathecal injections were noted, nor did any inadvertent epidural injections of

medications occur. No patient had respiratory depression (respiratory rate less than 10% for age). We

believe epidural administration of fentanyl by a carefully educated nursing staff is safe and effective in


SO - Southern Medical Journal 1992;85:384-38

UI - 000158

AU - Wilson JF

AU - Brockopp GW

AU - Kryst S

AU - Steger H

AU - Witt WO

TI - Medical students' attitudes toward pain before and after a brief course on pain [see comments]

AB - The effectiveness of a brief clinical and basic science seminar on pain for 1st year medical students was

examined by comparing attitudes about pain prior to the seminar to attitudes 5 months after the seminar. The

6-h course combined written materials conveying facts about behavioral, social and biological aspects of pain

with clinical observations of an acute and a chronic pain treatment team. Examination of responses to a

questionnaire assessing attitudes toward pain patients revealed that medical students have limited personal

experience with pain and medications for pain, and limited knowledge about pain. Pre-course attitudes

toward pain patients were dominated by perceived negative characteristics of pain patients and the belief that

working with such patients is difficult. Attitudes measured 5 months after the course reflected increased

complexity, greater emphasis that pain is real and not imaginary, and stronger belief that working with pain

patients is rewarding. Five months after the seminar, students reported more accurate estimates of the

frequency of problems with addiction stemming from acute pain treatment and exaggerated the prevalence of

pain problems in the society. The importance of integrating clinical and basic science experiences in order to

influence long-term clinical attitudes and produce lasting changes in clinically relevant knowledge is


SO - Pain 1992;50:251-25

UI - 000173

AU - Zenz M

AU - Strumpf M

AU - Tryba M

TI - Long-term oral opioid therapy in patients with chronic nonmalignant pain

AB - In contrast to the use of opioids for the treatment of acute and chronic cancer pain, the administration

of chronic opioid therapy for pain not due to malignancy remains controversial. We describe 100 patients

who were chronically given opioids for treatment of nonmalignant pain. Most patients experienced

neuropathic pain or back pain. We used sustained-release dihydrocodeine, buprenorphine, and sustained-

release morphine. Pain reduction was measured with visual analogue scales (VAS), and the Karnofsky

Performance Status Scale was used to assess the patient's function. Good pain relief was obtained in 51

patients and partial pain relief was reported by 28 patients. Only 21 patients had no beneficial effect from

opioid therapy. There was a close correlation between the sum and the peak VAS values (r = 0.983; p less

than 0.0001) and pain reduction was associated with an increase in performance (p less than 0.0001). The

most common side effects were constipation and nausea. There were no cases of respiratory

depression or addiction to opioids. Our results indicate that opioids can be effective in chronic

nonmalignant pain, with side effects that are comparable to those that complicate the treatment of cancer


SO - Journal of Pain & Symptom Management 1992;7:69-7

UI - 000017

AU - Zenz M

AU - Strumpf M

AU - Tryba M

TI - Long-term oral opioid therapy in patients with chronic nonmalignant pain

AB - IN: Universitatsklinik Bergmannsheil, Klinik fur Anaesthesiologie, Intensiv und Schmerztherapie,

Bochum, Germany LA: English AB: Chronically administered dihydrocodeine, buprenorphine, or morphine

to 100 patients (aged 29-81 yrs) with nonmalignant pain. Ss were administered the Visual Analogue Scale

(VAS), a performance status scale. Good pain relief was obtained in 51 Ss, and partial pain relief was

reported by 28 Ss. There was a close correlation between the sum and the peak VAS values, and pain

reduction was associated with an increase in performance. The most common side effects were constipation

and nausea. The case report of a 35-yr-old male is presented. Opioids can be effective in chronic

nonmalignant pain, with side effects that are comparable to those that complicate the treatment of cancer

pain. (PsycLIT Database Copyright 1992 American Psychological Assn, all rights reserved) KP: long term

dihydrocodeine or buprenorphine or morphine; pain relief & side effects; 29-81 yr olds with chronic

nonmalignant pain AN: 79-32549

SO - Journal of Pain and Symptom Management 1992;7:69-7

UI - 000022

AU - Abdelhamid EE

AU - Sultana M

AU - Portoghese PS

AU - Takemori AE

TI - Selective blockage of delta opioid receptors prevents the development of morphine tolerance and

dependence in mice

AB - IN: Alexandria U, Faculty of Science, Egypt LA: English AB: Studied the effect of the selective delta

antagonist naltrindole (NTI) and its nonequilibrium analog naltrindole 5'-isothiocyanate (5'-NTII) on the

development of morphine tolerance and dependence in male mice. Degree of morphine tolerance was

monitored by determining the ED-sub-5-sub-0 of morphine sulfate in a tail-flick antinociceptive assay;

degree of physical

dependence on morphine was assessed by estimating the amount of naloxone required to induce withdrawal

jumping. Both NTI and 5'-NTII suppressed the development of opiate tolerance and dependence in acute

and chronic models. The antagonists had no influence on the activity of the mu opioid receptor agonist

DAMGO. Thus, the inhibitory effect of NTI and 5'-NTII appeared to be due to their antagonist actions

solely on delta opioid receptors. Implications for the management of chronic pain are discussed. (PsycLIT

Database Copyright 1992 American Psychological Assn, all rights reserved) KP: naltrindole vs naltrindole 5-

isothiocyanate; development of morphine tolerance & dependence; male mice; implications for chronic pain

management AN: 79-00730

SO - Journal of Pharmacology and Experimental Therapeutics 1991;258:299-30

UI - 000116

AU - Boogaerts J

AU - Lafont N

TI - [Mechanism of action and clinical use of opioids administered by the peripheral perineural

route]. [Review] [French]

AB - Experimental studies have shown that opioids could produce two types of effect on neuronal

excitability. The first one, aspecific, is a local anesthetic action on the nerve fiber with a diminution of

sodium and potassium conductance. The second is specific: the sodium conductance lowering is due to a

linkage of the opioid with a receptor on the internal face of the membrane. Opioids could also migrate to the

posterior horn of the spinal cord after linkage with axonal receptors. Clinical studies have proved that

opioid injection in peripheral nervous trunks and specially in the brachial plexus produce a

prolonged analgesia status in the post operative period but also and mostly in the chronic pain. The

more liposoluble opioids like fentanyl and buprenorphine are the more effective. [References: 52]

SO - Cahiers d Anesthesiologie 1991;39:91-9

UI - 000117

AU - Eledjam JJ

AU - Viel E

AU - Bassoul B

AU - Bruelle P

TI - [Non-analgesic effects of opioids]. [Review] [French]

AB - The aim of the regional administration of opioids is to provide an efficient and prolonged analgesia.

Then, opiates can be useful for postoperative analgesia and for the treatment of chronic pain of malignant

origin. Analgesia is correlated with several adverse effects of which the most frequent are nausea and itching

and the most severe is respiratory depression. Beside the adverse effects, other properties of opiates could

be responsible of favourable effects which can be taken in advantage in specific indications. In the

postoperative period, epidurally administered opioid can attenuate the neuroendocrine and metabolic

responses to surgery and pain. This effect is responsible of a reduction of the resistance to insulin and of a

better nutritional balance, especially after major abdominal surgical procedures. Opioids also act by a

reduction of the motor functions of the bowel, which perhaps could reduce the incidence of anastomotic

breakdowns. Finally, other effects have been reported, as anecdotes, such as the treatment of spasm after

bilateral replantation of the ureters, neurologic bladder dysfunctions and enuresis. Spinal administration of

opioids has also been used as a treatment of premature ejaculation. [References: 41]

SO - Cahiers d Anesthesiologie 1991;39:111-11

UI - 000109

AU - Ferrell BA

AU - Ferrell BR

TI - Pain management at home. [Review]

AB - The management of chronic pain should be a priority in geriatric home care. Pain is a common

problem that has tremendous potential to influence the physical function and quality of life of elderly people

during their remaining years. The experience of pain and its management at home are not analogous to

institutional settings. Family and caregivers have important influences on pain management and may require

education and support for the long-term management of chronic pain patients. Existing pain management

strategies should be tailored to meet the special needs of geriatric patients and be sensitive to caregiver

concerns. Implications, indications, and applications for high-tech pain management strategies need to be

clarified for the management of older people at home. [References: 27]

SO - Clinics in Geriatric Medicine 1991;7:765-77

UI - 000122

AU - Fogel BS

AU - Fretwell MD

TI - Common mental health problems in geriatric practice. Part II: Insomnia, chronic pain, troubled

families, and other dilemmas

SO - Rhode Island Medical Journal 1991;74:68-7

UI - 000112

AU - Foldes FF

TI - Pain control with intrathecally and peridurally administered opioids and other drugs. [Review]

AB - Sharp pain is conducted rapidly by myelinated delta A fibers and diffused pain slowly by

nonmyelinated C fibers to pseudobipolar neurons in the posterior ganglion and

from there to neurons located in the posterolateral horn of the spinal cord. From here on nociferous impulses

are transmitted by excitatory peptides (e.g. substance P) or amino acids (e.g. glutamate, aspartate) through

interconnecting neurons of the pain pathways, primarily on the contralateral side, to the brain stem and from

there to the sensory cortex, where they are appreciated and acted upon. There are specific inhibitory

receptors located on axon terminals, near to the release sites of the excitatory amino acids and peptides.

Stimulation of these receptors by their appropriate ligands such as endogenous (e.g. enkephalis, endorphins)

or exogenous opioids, clonidine, serotonin, somatostatin inhibits the release of excitatory neurotransmitters

and relieves pain. There are at least 3 different opioid receptors, called mu-, kappa- and delta-receptors in

the spinal cord. These can be differentiated from one another by their specific affinity toward different

endogenous or exogenous opioids and the pure narcotic antagonist, naloxone. It appears that the nociferous

impulses transmitted by parallel pathways equipped with different inhibitory receptors have to be integrated

to produce pain sensation and partial inhibition of transmission in different pathways or complete inhibition

in one of the pathways may relieve pain. In recent years the concept of "selective spinal analgesia" has been

applied clinically for the relief of postoperative, obstetrical and chronic pain. At first it was expected that the

intrathecal or peridural administration of morphine will produce analgesia without the side effects of

systemically administered morphine. It soon became evident, however, that intrathecally and peridurally

administered morphine after several hours of delay reaches the fourth ventricle and by stimulating mu-

receptors may cause respiratory depression and other undesired effects (e.g. nausea, vomiting, pruritus).

Several different approaches are being investigated for the production of selective spinal analgesia without

side effects. They include: a. the use of more lipophilic, long-lasting opioids (e.g. lofentanil) which would be

almost completely absorbed by the spinal cord and therefore would not reach the medullary centers; b. the

development of opioids with specific affinity to kappa- and for delta- and little or no affinity to mu-

receptors, primarily responsible for side effects; and c. combining lower doses of opioid agonists with alpha

2-adrenergic agonists (e.g. clonidine) or with somatostatin. It is conceivable that in the not-too-distant

future, it will be possible to achieve through these measures, selective spinal analgesia without side effects.

[References: 68]

SO - Anaesthesiologie und Reanimation 1991;16:287-29

UI - 000118

AU - Forman WB

AU - Stratton M

TI - Current approaches to chronic pain in older patients. [Review]

AB - As the population ages, primary care physicians face an increasing number of individuals who suffer

from the effects of chronic diseases, including the accompanying chronic pain. This article reviews the

common causes of pain in the elderly and suggests a system for assessing its severity. Five different

approaches to treating pain in this population are outlined, as are guidelines for managing the potential side

effects of treatment. [References: 20]

SO - Geriatrics 1991;46:47-5

UI - 000171

AU - Hassenbusch SJ

AU - Stanton-Hicks MD

AU - Soukup J

AU - Covington EC

AU - Boland MB

TI - Sufentanil citrate and morphine/bupivacaine as alternative agents in chronic epidural infusions

for intractable non-cancer pain

AB - Intraspinal narcotic (usually intrathecal morphine) infusions with implanted pumps are increasingly

used in patients with intractable chronic pain not caused by cancer. In some patients, pain control is difficult

with infusions of morphine. Seven patients with diagnoses of arachnoiditis, epidural scarring, and/or

vertebral body compression fracture were treated with alternative solutions in an epidural route. For

maximal flexibility, Medtronic implanted programmable infusion pumps with catheters to T6-T10 were used,

and pain was monitored by verbal pain scales. In three patients, epidural infusions of morphine in 0.5%

bupivacaine (MS-MARC) resulted in little or no pain relief without significant side effects (e.g., headache,

nausea, or vomiting). In these same patients, epidural infusions of sufentanil citrate resulted in pain scale

reductions of 92%, 82%, and 40%, respectively, with no side effects. Four other patients found more

effective pain relief when switched from initial sufentanil citrate infusions to MS-MARC. Pain scale

reductions (with no side effects) were 92%, 76%, 59%, and 47% in these patients. Pain relief and minimal

side effects with sufentanil citrate is theorized to result from its higher lipophilicity promoting local

transdural diffusion to spinal cord and limiting upward diffusion to the brain stem. Sufentanil citrate is also

advantageous for programmable pumps because it is 100 times more potent than morphine and therefore

allows longer pump refill times and higher infusion doses. Although this study was done on a limited number

of patients, sufentanil citrate and MS-MARC in epidural infusions using programmable infusion pumps for

non-cancer patients provide significant alternative drug combinations and routes.

SO - Neurosurgery 1991;29:76-81; discussion 81-

UI - 000252

AU - Hogan O

AU - Weissman DE

AU - Haddox JD

AU - Abram S

AU - Taylor ML

AU - Janjan N



AB - AB - The Medical College of Wisconsin multispecialty cancer pain service reviewed its experiences

with epidural analgesia by retrospectively reviewing hospital/clinic charts from January 1987 through

December 1989. 1205 patients (pts) were admitted to the inpatient oncology service during the study period,

and epidural analgesia was used 16 times (15 pts, 1.2%). Indications for epidural analgesia included failure

of systemic opioids and other noninvasive drug and nondrug therapies per WHO guidelines. The mean pre-

epidural equianalgesic dose of im morphine was 300 mg/day. Temporary catheters were used to assess

response to epidural morphine; if no response bupivacaine was added; if no response the catheter was

removed; if analgesia was obtained the temporary catheter was replaced by a tunneled catheter for long-term

use. Analgesia was successfully obtained in 12/16 epidural attempts; 6 with morphine alone, 6 with morphine

plus bupivacaine. 4/16 attempts were discontinued due to unacceptable toxicity or technical problems.

Tunneled catheters were used for a mean of 83 days (range 6-965 days). Catheter problems included

malfunction (7), infection (4), injection pain (4), epidural hematoma (1), hyperesthesia (1). Epidural

analgesia is infrequently indicated, bupivacaine extends the efficacy of epidural analgesia and complications

are common AD - Medical Coll. of Wisconsin AD - Milwaukee AD - WI 53211 UI - 91672498

SO - Proc Annu Meet Am Soc Clin Oncol 1991;10:A1161-A116

UI - 000170

AU - Hoskin PJ

AU - Hanks GW

TI - Opioid agonist-antagonist drugs in acute and chronic pain states. [Review]

AB - The agonist-antagonist opioid analgesics are a heterogeneous group of drugs with moderate to strong

analgesic activity comparable to that of the pure agonist opioids such as codeine and morphine but with a

limited effective dose range. The group includes drugs which act as an agonist or partial agonist at one

receptor and an antagonist at another (pentazocine, butorphanol, nalbuphine, dezocine) and drugs acting as a

partial agonist at a single receptor (buprenorphine). These drugs can be classified as nalorphine-like or

morphine-like. Meptazinol does not fit into either classification and occupies a separate category.

Pentazocine, butorphanol and nalbuphine are weak mu-antagonists and kappa-partial-agonists. All three

drugs are strong analgesics when given by injection: pentazocine is one-sixth to one-third as potent as

morphine, nalbuphine is slightly less potent than morphine, and butorphanol is 3.5 to 7 times as potent. The

duration of analgesia is similar to that of morphine (3 to 4 hours). Oral pentazocine is closer in analgesic

efficacy to aspirin and paracetamol (acetaminophen) than the weak opioid analgesics such as codeine.

Neither nalbuphine nor butorphanol is available as an oral

formulation. At usual therapeutic doses nalbuphine and butorphanol have respiratory depressant effects

equivalent to that of morphine (though the duration of such effects with butorphanol may be longer). Unlike

morphine there appears to be a ceiling to both the respiratory depression and the analgesic action. All of

these 3 drugs have a lower abuse potential than the pure agonist opioid analgesics such as morphine.

However, all have been subject to abuse and misuse, and pentazocine (but not the others) is subject to

Controlled Drug restrictions. Buprenorphine is a potent partial agonist at the mu-receptor, and by

intramuscular injection is 30 times as potent as morphine. A ceiling to the analgesic effect of buprenorphine

has been demonstrated in animals and it is also claimed in humans. However, there are no reliable data

available to define the maximal dose of buprenorphine in humans. A practical ceiling exists for sublingual use

in that the only available formulation is a 2 micrograms tablet and few patients will accept more than 3 or 4

of these in a single dose. The duration of analgesia is longer than that of morphine, at 6 to 9 hours. There

have been suggestions that buprenorphine causes less respiratory depression than morphine, but viewed

overall it appears that in equianalgesic doses the 2 drugs have similar respiratory depressant

effects.(ABSTRACT TRUNCATED AT 400 WORDS) [References: 118]

SO - Drugs 1991;41:326-34

UI - 000113

AU - Mendelson G

AU - Mendelson D

TI - Legal aspects of the management of chronic pain [published erratum appears in Med J Aust 1991

Dec 2-16;155(11-12):856]

AB - OBJECTIVE: To review the legal provisions which control the prescription of opioid analgesics in

Australia, and to summarise the areas in which practitioners who treat patients with chronic pain may expect

to become involved with the legal system. DATA SOURCES: The relevant legislation was reviewed, and a

selective review was undertaken of literature dealing with the legal aspects of pain and suffering which may

form a basis for personal injury claims. Case law which deals with issues of consent to treatment was also

examined. DATA SYNTHESIS: Statutory requirements which control the prescription of opioids were

summarised. Leading cases on patient consent were discussed to clarify for the practitioner the principles

which the Courts use in the assessment of the validity of the consent given by patients for treatment. The

assessment of the pain patient involved in litigation was briefly discussed. CONCLUSIONS: The

prescription and administration of opioid analgesics must be in accordance with the legislative provisions.

Treatment options must be discussed and explained to patients so that valid consent can be obtained.

Patients' questions must be answered in full, and documentation in the clinical record is required

SO - Medical Journal of Australia 1991;155:640-64

UI - 000110

AU - Merry AF

AU - Schug SA

AU - Richards EG

AU - Large RG

TI - Opioids in the treatment of chronic pain of nonmalignant origin

SO - New Zealand Medical Journal 1991;104:520-52

UI - 000121

AU - Pendergrass JS

TI - Epidural analgesia: a viable option for pain control

AB - Epidural analgesia is an important intervention for both acute and chronic pain management. It has

been in use since the early 1900s, but the technique using local application of opiate analgesics has only been

in use since the late 1970s (Moulin & Coyle, 1986). Today, many patients receive epidural analgesia for

postoperative pain control, and its use for acute or chronic pain management in a hospital, pain clinic, or

home setting also continues to increase. Epidural analgesia is also being utilized to manage acute pain in the

pediatric client. Epidural analgesia requires meticulous techniques, beginning with placement of the epidural

catheter and continuing with administration of medications and nursing management of the catheter. Nursing

assessment and development of protocols along with preoperative and postoperative patient and family

teaching are vital components of the total plan of care. The nurse practitioner (NP) or other health care

provider must be cognizant of safety considerations, whether in the hospital environment, pain clinic, or

home setting.

SO - Journal of the American Academy of Nurse Practitioners 1991;3:25-2

UI - 000119

AU - Pincus DF

TI - When and why I use pethidine

AB - Pethidine is a valuable drug in general practice. It is useful in the acute pain of trauma and renal or

biliary colic. It should be used by intramuscular injection, not orally. It should not be used for chronic pain,

malignancy, head injury, heart failure, undiagnosed acute abdominal pain and if opiate addiction is suspected

SO - Australian Family Physician 1991;20:392, 394-392, 39

UI - 000123

AU - Poniatowski BC

TI - Continuous subcutaneous infusions for pain control

AB - Chronic moderate-to-severe pain is a common problem that directly impacts on the quality of life of

the patient with a malignant neoplasm. It is estimated that pain is a major symptom in 70% of cancer

patients. Continuous subcutaneous infusion of opioids has proved to be an efficacious and safe method to

control the chronic pain of the home-bound and hospitalized patient. A wide variety of opioids can be used,

including morphine, hydromorphone, and methadone. The subcutaneous route offers economic as well as

physiologic advantages. The primary disadvantage to the system is volume limitations. Competent nursing

management of the subcutaneous infusion helps to maximize the effectiveness of the opioid, thereby

improving the patient's quality of life

SO - Journal of Intravenous Nursing 1991;14:30-3

UI - 000115

AU - Richlin DM

TI - Nonnarcotic analgesics and tricyclic antidepressants for the treatment of chronic nonmalignant


AB - Chronic nonmalignant pain is often characterized by multiple treatment failures, a pattern of

maladaptive behavior, and depression. Often there is a history of inappropriate and excessive use of

medications for pain. Prior and ongoing use of narcotics and sedatives acts to compound and aggravate the

chronic pain syndrome. A first step in treatment is controlled withdrawal of these agents. Nonnarcotic

analgesics, NSAIDs, and tricyclic antidepressants are commonly employed in patients with chronic pain.

Effective use of these agents requires understanding of their pharmacokinetic and pharmacodynamic

properties. Use of a fixed-time schedule is necessary to achieve an effective, sustained therapeutic response.

Careful patient education and monitoring for side effects and toxicity are necessary, particularly in the

elderly and patients with coexisting medical disorders. Incidence of side effects and toxicity may be reduced

by choice of drug and modification of dosing regimen. Nonnarcotic analgesics, TCAs, and NSAIDs are

seldom effective by themselves in resolving the pain and distress of patients with chronic nonmalignant pain.

This is particularly true when maladaptive behavior coexists. A comprehensive multimodal pain management

program encompassing additional pain-relieving strategies and behavior-modifying techniques should be

considered and utilized in conjunction with medication.

SO - Mount Sinai Journal of Medicine 1991;58:221-22

UI - 000114

AU - Schug SA

AU - Merry AF

AU - Acland RH

TI - Treatment principles for the use of opioids in pain of nonmalignant origin. [Review]

AB - Inadequately treated acute and chronic pain remains a major cause of suffering, in spite of enormous

advances in pharmacology and technology. Opioids provide a powerful, versatile, widely available means of

managing this pain, but their use is too often restrained by ignorance and mistaken fears of addiction. The

management of postoperative pain (perhaps the most common form of acute pain) is traditionally attempted

with fixed dosages of analgesics by relatively unpredictable routes (e.g. oral, rectal and intramuscular).

Intravenous opioid infusions (an improvement) risk respiratory depression and require close monitoring and

titration. Patient-controlled analgesia (PCA), by contrast, permits the most efficacious medication (pure

opioid agonist) by the optimal route (intravenous) under direct control of the patient, and provides high

levels of satisfaction and safety. Ideally, any opioid use should be integrated with a wide spectrum of other

analgesic modalities in an anaesthesiology-based 'acute pain service'. The use of opioids for chronic pain of

nonmalignant origin remains controversial. There is a perceived conflict between patients' interests and those

of society. However, problems (such as tolerance, physical dependence, addiction and chronic toxicity),

anticipated from experience with animal experiments and pain-free abusers, seldom cause difficulties when

opioids are used appropriately to treat pain (so-called 'dual pharmacology'). With sensible guidelines, and in

the context of a multidisciplinary pain clinic, opioids may provide the only hope of relief to many sufferers of

chronic pain. [References: 88]

SO - Drugs 1991;42:228-23

UI - 000111

AU - Schwartz RH

AU - Johnson NP

AU - Hornung CA

AU - Phelps GL

AU - Berg EW

TI - Awareness of substance abuse in orthopedic patients: a survey of orthopedic surgeons

AB - We surveyed 178 orthopedic physicians in the Washington, DC, area to ascertain the effect on patient

care of previous education in the area of drug and alcohol issues. The return rate was 75%. Of the

respondents, 99% were male, average age was 46.7 years (+/- 9.3), and average number of years in practice

was 15.2 (+/- 9.6). A majority of respondents indicated that they did not have training in the abuse

potential of analgesics (92 [69%]), characteristics of benzodiazepine abuse (77 [58%]), or when to

seek the assistance of an addiction medicine specialist for patients with chronic pain (106 [80%]).

Only 41 (31%) of the orthopedists indicated that they inquire about alcohol and drug use before prescribing

opiates for more than a week. We offer suggestions for self-education for interested physicians

SO - Southern Medical Journal 1991;84:1455-145

UI - 000020

AU - Tennant F

AU - Shannon JA

AU - Nork JG

AU - Sagherian A

TI - Abnormal adrenal gland metabolism in opioid addicts: Implications for clinical treatment

AB - IN: Research Ctr for Dependency Disorders & Chronic Pain, West Covina, CA, US LA: English AB:

Examined whether methadone maintenance treatment (MMT) causes diminution of pituitary-adrenal reserve

or if that condition preexists in the heroin addict. Ss were 14 male heroin addicts who voluntarily sought

outpatient detoxification. Results indicate that most active heroin addicts have low adrenal reserve prior to

entering MMT. Chronic opioid administration may induce adrenal insufficiency or an addisonian state. There

is a need to normalize adrenal gland metabolism during treatment of heroin addicts. (PsycLIT Database

Copyright 1992 American Psychological Assn, all rights reserved) KP: abnormal adrenal gland metabolism

as preexisting condition vs methadone maintenance side effect; male heroin addicted patients in

detoxification AN: 79-24914

SO - Journal of Psychoactive Drugs 1991;23:135-14

UI - 000021

AU - Toro R

AU - Perez Infante M

TI - Treatment of chronic pain with LARQ 731, a new alternative to opiate analgesics

AB - IN: Inst Venezolano de los Seguros Sociales, Hosp General "Miguel Perez Carreno" Servicio de

Anestesiologia, Caracas, Venezuela LA: English AB: LARQ 731 (a drug combination of carisoprodol,

dipyrone, and salicylamide) was administered to 42 36-88 yr old patients with advanced cancer who

complained of severe pain and who required frequent medication with opiate analgesics. To test the

analgesic efficacy of the combination, the arm-cuff method was used before and after drug administration to

evaluate the pain threshold. A large increase in pain threshold after LARQ 731 administration was observed.

No significant changes were found in routine laboratory examinations, blood pressure, heart, or breathing

rate. (PsycLIT Database Copyright 1992 American Psychological Assn, all rights reserved) KP: carisoprodol

& dipyrone & salicylamide; analgesic efficacy & pain thresholds; 36-88 yr old cancer patients with severe

pain AN: 79-10330

SO - Current Therapeutic Research 1991;49:187-19

UI - 000018

AU - Verhaag DA

AU - Ikeda RM

TI - Prescribing for chronic pain. Special Issue: Prescription drug issues: Public policy and clinical


AB - IN: Medical Board of California, Sacramento, US LA: English AB: Offers guidelines in the following

areas for physicians who treat patients with chronic intractable pain with opiates: history and medical

examination, diagnosis/medical indication, written treatment plan with recorded measurable objectives,

informed consent, periodic reviews and modifications, consultation, and record keeping. (PsycLIT Database

Copyright 1992 American Psychological Assn, all rights reserved) KP: opiate prescription guidelines for

chronic pain patients; physicians AN: 79-32546

SO - Journal of Psychoactive Drugs 1991;23:433-43

UI - 000024

AU - Weingarten MA

TI - Chronic opioid therapy in patients with a remote history of substance abuse

AB - LA: English AB: Presents 2 cases of male patients with a history of substance abuse who were

successfully maintained on narcotics for chronic pain problems, without escalation of dose or abuse. It is

suggested that the criteria proposed by R. K. Portenoy (see PA, Vol 77:23432) for institution of narcotic

maintenance in chronic pain patients should not be considered absolute. (PsycLIT Database Copyright 1991

American Psychological Assn, all rights reserved) KP: chronic narcotic therapy; chronic pain; male patients

with history of substance abuse; case reports AN: 78-16376

SO - Journal of Pain and Symptom Management 1991;6:2-

UI - 000255

AU - Weissman DE

AU - Joranson DE

AU - Hopwood MB

TI - Wisconsin physicians' knowledge and attitudes about opioid analgesic regulations

AB - AB - [No Abstract Available] AD - Division of Cancer and Blood Diseases AD - Medical College of

Wisconsin AD - Milwaukee 53226 UI - 93118350

SO - Wis Med J 1991;90:671-67

UI - 000253

AU - Weissman DE

AU - Joranson DE

AU - Hopwood M



AB - AB - 200 Wisconsin Mds chosen at random were mailed a survey in June 1990 to assess

knowledge/attitudes concerning regulatory law. 90 surveys (45%) were evaluable for review, including

internists (27), surgeons (25), family practitioners (19), other (19). MDs had poor knowledge of drug

schedule and number of allowable refills of seven different opioids. 32% of MDs did not know that an

emergency supply of a schedule II drug could be prescribed by telephone. MDs were very concerned about

possible investigation when using opioids: 15, 17 and 19 times more concerned about prescribing morphine,

hydromorphone and methadone, respectively, than when prescribing codeine with acetaminophen. MDs

were 8 times more concerned about possible investigation when using opioids to treat chronic cancer pain

than when using opioids for acute pain and 20 times more concerned if the patient had a history of drug

abuse, even with a 'real' reason to have pain. MDs were less concerned about investigation than about

addiction, tolerance or respiratory depression. Wisconsin MDs have serious concerns about using opioid

analgesics and poor knowledge of regulatory laws. Education is needed to lessen these fears, especially as

they apply to the treatment of cancer-related pain AD - Medical Coll. of Wisconsin AD - Milwaukee AD -

WI 53211 UI - 91672474

SO - Proc Annu Meet Am Soc Clin Oncol 1991;10:A1129-A112

UI - 000120

AU - Yue SK

AU - St.Marie B

AU - Henrickson K

TI - Initial clinical experience with the SKY epidural catheter

AB - The new SKY epidural catheter was evaluated, based upon information collected about implant and

use of 53 catheters by 51 patients. Catheters were used to treat chronic pain of a malignant (n = 25) and

nonmalignant (n = 28) origin. Of 3450 treatment days, 89% occurred at home. Mean catheter use for

malignant and nonmalignant conditions were 58.6 and 76.3 days/patient, respectively. Visual analogue pain

scores in the first wk after implant indicated 79% of patients achieved good to excellent pain relief. Clinical

impressions indicated this group achieved substantial long-term pain relief. No serious complications were

observed. Two types of leakage required removing 5 catheters, prompting changes that eliminated

subsequent leakages of both types. Accidental patient retraction and subcutaneous infection each required a

catheter removal. No subarachnoid or epidural infections occurred. The SKY catheter proved to be safe and

reliable. Therapy was cost-effective, since patients achieved substantial pain relief while treated at home

SO - Journal of Pain & Symptom Management 1991;6:107-11

UI - 000174

AU - Zenz M

AU - Sorge J

TI - Is the therapeutic use of opioids adversely affected by prejudice and law?. [Review]

SO - Recent Results in Cancer Research 1991;121:43-5

UI - 000142

AU - Allen A

TI - Notes from the annual meeting of the American Society of Anesthesiologists

AB - Several important developments were reported at the 1989 Annual Meeting of the American Society

of Anesthesiologists: (1) a computerized machine called HealthQuiz asks patients health questions, and in

less than 10 minutes provides a printout of answers, a summary of symptoms, and a list of suggested

laboratory tests; (2) a simple device provides continuous measurements of a critically ill patient's oxygen and

carbon dioxide levels; (3) near-infrared reflectance is a new technique that may provide the first accurate

real-time measurement of critical oxygen levels in the brain; (4) pulse oximeters may provide false readings

in patients who smoke cigarettes; (5) a new test may accurately predict the survival chances of a child in a

coma; (6) the fastest growing subspecialty in anesthesiology is chronic pain management clinics; (7) alpha-2

adrenergic agonists improve pain relief without the unwanted side effects of narcotics; (8) clonidine appears

to suppress the dangerous shivering that often occurs in postanesthesia patients; (9) flumazenil was

successfully tested as an agent to reverse the drowsiness caused by midazolam; and (10) ephedrine

minimizes nausea and vomiting in patients undergoing ambulatory surgery

SO - Journal of Post Anesthesia Nursing 1990;5:96-10

UI - 000136

AU - Cole L

AU - Hanning CD

TI - Review of the rectal use of opioids. [Review]

AB - The rectal route for the administration of opioid analgesics is often forgotten by physicians seeking

alternatives to the oral route. This article reviews the physiology of rectal drug absorption and such data as

exists on the different opioids that have been administered by this route. Conventional fatty-based

suppositories have a place in the management of chronic pain but the variability in dissolution and drug

absorption limit their usefulness. Recently, sustained release vehicles have become available that offer the

prospect of the attainment of steady analgesic drug concentrations with once or twice daily dosing. Early

studies with the morphine hydrogel suppository suggest that it may be capable of fulfilling this prospect.

Their inherent safety, as dose-dumping is impossible, will make them suitable for use in the home.

[References: 43]

SO - Journal of Pain & Symptom Management 1990;5:118-12

UI - 000201

AU - Coyle N

AU - Adelhardt J

AU - Foley KM

AU - Portenoy RK

TI - Character of terminal illness in the advanced cancer patient: pain and other symptoms during

the last four weeks of life [see comments]

AB - AB - There is a great variability among advanced cancer patients in the experience of symptoms and

their impact on life's activities. A subgroup of difficult patients particularly tax the clinical skills and

compassion of practitioners. Although the need for information about these patients is evident, their

characteristics have not been explored heretofore. We describe our experience with such patients, a group

referred to the Supportive Care Program of the Pain Service at Memorial Sloan-Kettering Cancer Center.

Prevalence of pain and other symptoms, patterns of opioid use and routes of drug administration, and the

prevalence of suicidal ideation and requests for euthanasia are discussed UI - 90270702

SO - J Pain Symptom Manage 1990;5:83-9

UI - 000127

AU - Devulder J

AU - De Colvenaer L

AU - Rolly G

AU - Caemaert J

AU - Calliauw L

AU - Martens F

TI - Spinal cord stimulation in chronic pain therapy

AB - Spinal cord stimulation was undertaken in 45 patients referred to the University Hospital in Ghent.

Failed back surgery was the major indication for implantation. Raynaud's phenomenon, causalgia,

polyneuropathy, phantom limb pain, and diverse causes were the other indications. Before neurosurgical

implantation of the system, a percutaneous epidural trial procedure was performed. The efficacy of the

implanted stimulation system was estimated by considering the use of medication and the patients' personal

appreciation of the obtained pain relief. Thirty-five patients experienced very good pain relief. Only two

patients needed further narcotic analgesics. Eight patients stopped using the stimulation system. To ensure

good results, strict selection criteria and many surgical reinterventions seemed to be necessary. Although

spinal cord stimulation is a nonablative technique, many complications may occur

SO - Clinical Journal of Pain 1990;6:51-5

UI - 000131

AU - Eriksen J

AU - Jensen NH

AU - Frolich S

TI - [Why are chronic pain patients given opioids via injections? (letter)]. [Danish]

SO - Ugeskrift for Laeger 1990;152:3181-318

UI - 000135

AU - Finley RS

TI - Pain management with spinally administered opioids. [Review]

AB - The use of spinally administered opioids to manage pain is discussed. Central action on opioid

receptors of the substantia gelatinosa allows opioids to be administered spinally for pain originating

anywhere inferior to the cranial nerves. Spinal opioids are most commonly administered for intractable

midline sacral and perineal pain. The best candidates for spinal opioids are patients in whom appropriate

"conventional" therapy no longer provides adequate relief, patients who experience severe adverse effects

from conventional therapy, and patients for whom alternative anesthetic procedures are inappropriate or

have failed. A reasonably safe initial dose is morphine sulfate 1 mg intrathecally. The availability of

preservative-free, concentrated morphine sulfate enables larger doses to be safely and comfortably

administered. Increased dosage requirements may result from tolerance, progression of disease, increased

systemic absorption, or slippage of the catheter tip. As with systemically administered opioids, care must be

exercised when discontinuing spinal opioid therapy. Adjuvant drugs used with spinal opioids include

systemically administered analgesics, antidepressants, corticosteroids, and spinal local anesthetics. The

administration of spinal opioids with systemic opioids or other CNS depressants may result in excessive

sedation, respiratory depression, nausea, vomiting, constipation, pruritus, and other adverse effects. Spinally

administered opioids can be used to manage severe chronic pain effectively, safely, and comfortably.

[References: 29]

SO - American Journal of Hospital Pharmacy 1990;47:S14-S1

UI - 000143

AU - Gostomzyk JG

AU - Heller WD

TI - [Long-term use of narcotics in pain therapy]. [German]

AB - From 1. 1. 1976 to 30. 6. 1987, a total of 25,611 prescriptions for narcotics were obtained from

pharmacies by 4131 persons living in a town of 250,000 inhabitants in the Federal Republic of Germany.

2412 patients (58.4%) had been prescribed narcotics on only one occasion, 3178 patients (76.9%) over a

limited period of six months, presumably for acute pain. Only 520 patients (12.6%) received, over a period

of at least six months, five or more narcotic prescriptions per six months. Reasons for the latter prescriptions

were malignant tumours in 273 (6.6%) and chronic pain due to benign diseases in 144 (3.5%). In 21 patients

(0.5%) the narcotic dosage had risen over two years, presumably because of the development of tolerance.

19 patients had been on narcotics for at least eight years, without their doctor diagnosing addiction. The

data suggest that, in prescribing narcotics for patients with incurable disease, the risk of addiction should

play no role

SO - Deutsche Medizinische Wochenschrift 1990;115:763-77

UI - 000133

AU - Hansberry JL

AU - Bannick KH

AU - Durkan MJ

TI - Managing chronic pain with a permanent epidural catheter

SO - Nursing 1990;20:52-5

UI - 000141

AU - Hassenbusch SJ

AU - Pillay PK

AU - Magdinec M

AU - Currie K

AU - Bay JW

AU - Covington EC

AU - Tomaszewski MZ

TI - Constant infusion of morphine for intractable cancer pain using an implanted pump [see


AB - In the past, pain control for chronic pain syndromes using narcotic infusion has been carried out

primarily via the intrathecal (subarachnoid) route. This report presents one of the first large series of

terminally ill cancer patients with intractable pain treated with continuous epidural morphine infusions by

means of implanted pumps and epidural spinal catheters. The purpose of the study was to demonstrate that

the epidural route is effective with minimal complications, and that screening with temporary epidural

catheter infusions results in a high rate of subsequent pain relief. A multidisciplinary team (neurosurgeon,

anesthesiologists, psychiatrists, oncologists, and nurse clinicians) evaluated and treated all of the patients

studied. Percutaneous placement of temporary epidural catheters for a trial assessment was performed by the

anesthesiologists. Pain evaluations were conducted independently by psychiatrists using both verbal and

visual analog scales. From 1982 to 1988, 41 (59.4%) of 69 patients evaluated for eligibility experienced

good pain control during trial assessment and were subsequently implanted with Infusaid infusion pumps.

Preinfusion pain analog values were 8.6 +/- 0.3 and postimplantation values at 1 month were 3.8 +/- 0.4 (p

less than 0.001). Over this same 1-month period. requirements of systemic morphine equivalents decreased

by 79.3% with epidural infusions as compared to preinfusion requirements (p less than 0.001). There were

no instances of epidural scarring, respiratory depression, epidural infections, meningitis, or catheter

blockage. One patient developed apparent drug tolerance and three patients required further catheter

manipulations. This series strongly suggests that significant reductions in cancer pain can be obtained with

few complications and a low morphine tolerance rate using chronic epidural morphine infusion.

Anesthesiology and psychiatry input, along with temporary catheter infusion screening and quantitative pain

evaluations using analog scales, are essential

SO - Journal of Neurosurgery 1990;73:405-40

UI - 000138

AU - Juul A

AU - Pedersen AT

TI - [Endogenous opioids and their therapeutic use in the treatment of pain]. [Review] [Danish]

AB - Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the

analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients

following epidural or intrathecal administration of endogenous opioids. Further investigations are required.

[References: 30]

SO - Ugeskrift for Laeger 1990;152:372-37

UI - 000023

AU - Kennedy JA

AU - Crowley TJ

TI - Chronic pain and substance abuse: A pilot study of opioid maintenance

AB - IN: U Colorado School of Medicine, Addiction Research & Treatment Services, Denver, US LA:

English AB: Presents a pilot study of methadone maintenance treatment for 4 patients (aged 27-38 yrs) with

both chronic pain and substance abuse. The study evaluated the program's ability to attract and hold patients,

the methodology for assessing change, and the problems and pitfalls. Weekly random urinalysis, weekly

psychotherapy, and quarterly self-report tests of pain, mood, and function were used to evaluate change.

Three patients remained in treatment for 19-21 mo. Two stopped needle use and substance abuse, and the

3rd stopped cocaine use and abusing the medical system to obtain opioids. All Ss appeared to have improved

functionally. (PsycLIT Database Copyright 1991 American Psychological Assn, all rights reserved) KP:

methadone maintenance; substance abusing 27-38 yr olds with chronic pain AN: 78-16651

SO - Journal of Substance Abuse Treatment 1990;7:233-23

UI - 000125

AU - King SA

AU - Strain JJ

TI - Benzodiazepine use by chronic pain patients

AB - Of 114 patients presenting to the Pain Management Service at the Mount Sinai School of Medicine

with chronic pain, 38% (N = 43) were taking one or more benzodiazepine drugs at the time of the initial

assessment. The majority of patients were chronic users, with 14% (N = 6) having taken the medications for

1-2 years and 46% (N = 20) for 2 years or longer. Ninety-three percent (N = 40) of those given a

benzodiazepine drug stated that it was initiated after the onset of pain. Although 86% (N = 37) were using

the medication (all or in part) to improve sleep, they continued to report as many problems with sleep as the

nonbenzodiazepine group did. Other drugs prescribed concurrently with the benzodiazepine drugs were

narcotic drugs (58% of patients), antidepressant drugs (32%), nonsteroidal antiinflammatory agents (26%),

and others (16%). Benzodiazepines have been reported to provide little therapeutic benefit to chronic pain

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patients, and may even exacerbate their symptoms. We have shown that benzodiazepine drugs are frequently

prescribed for long-term use, for sleep, and in conjunction with narcotic drugs. Such use is contrary to

generally accepted guidelines

SO - Clinical Journal of Pain 1990;6:143-14

UI - 000134

AU - Koeller JM

TI - Understanding cancer pain. [Review]

AB - The pathogenesis of cancer pain, the incidence of pain associated with specific types of malignant

tumors, and the nature of acute and chronic pain are discussed, and alternative delivery systems for pain

management are described. More than 80% of cancer patients with advanced metastatic disease suffer

moderate to severe pain. Most cancer pain is caused by direct tumor infiltration; approximately 20% of

cancer pain may be attributed to the effects of surgery, radio-therapy, or chemotherapy. The incidence of

cancer pain is related to tumor type; 70% or more of patients with tumors of the bone, cervix, and ovaries

suffer cancer-related pain, while only 5% of patients with leukemia have pain. Pain is defined by the organs

involved. Somatic pain is usually dull and well localized; visceral pain is generalized and difficult to describe.

Other types of pain, including deafferentation pain and referred pain, are particularly difficult to manage.

Cancer pain may be acute or chronic. The latter may cause psychological reactions that make effective

treatment more challenging. Opiate analgesic agents, administered by the epidural or intrathecal routes,

block pain more selectively and produce fewer adverse reactions than systemic analgesic agents. The

duration and onset of analgesia depend on the lipophilicity of the agent used. Because pain is the most

common complaint of the patient with cancer, clinicians should be aware of the range of pharmacologic and

nonpharmacologic analgesic modalities available to them. Familiarity with newer modalities and delivery

routes, such as spinal administration of opiate analgesics, is recommended. [References: 6]

SO - American Journal of Hospital Pharmacy 1990;47:S3-S

UI - 000139

AU - Lee TL

AU - Kumar A

AU - Baratham G

TI - Intraventricular morphine for intractable craniofacial pain

AB - This case management report on a patient with advanced craniofacial neoplasm discusses the

successful treatment of chronic pain by the cortical intraventricular narcotic administration. A previously

treated patient with surgery and radiotherapy for carcinoma of the palate developed severe intractable pain

despite high dose oral morphine therapy. Investigations revealed that neoplasm had reoccurred with

extensive infiltration. Intraventricular morphine therapy was discussed and accepted by the patient and

family. A ventricular shunt with an Ommaya reservoir was inserted under local anaesthesia. Preservative-free

morphine sulphate in increasing doses of 0.25 to 1 mg was administered, once daily, which kept the patient

in a pain-free state. The treatment was initiated in the hospital and continued at home till the demise of the

patient on the 9th week. The home care was provided by the nurses of Home Nursing Foundation and

Singapore Cancer Society under physician supervision. There were no complications which had been

reported in the literature, observed in the management of this patient

SO - Singapore Medical Journal 1990;31:273-27

UI - 000124

AU - Lipman AG

TI - Clinically relevant differences among the opioid analgesics. [Review]

AB - The mechanism of action of opioids and clinically relevant differences among the opioid analgesics are

described. Both endorphins (endogenous morphine-like substances) and exogenous opioids (opium alkaloids

and their derivatives) bind to opioid receptors in the human central nervous system to provide analgesia and

other effects. Some drugs, such as morphine, are true agonists, i.e., they bind to and activate receptors.

Some are partial agonists, binding to part of the receptor and causing effects that are similar to, but perhaps

less pronounced than, the effects produced by agonists. Others are antagonist, i.e., they bind to the receptor

but do not cause the associated effects. Some drugs, termed agonist-antagonist opioids, act as antagonists at

one type of receptor and agonists at another type of receptor. True agonists tend to have relatively straight-

line dose-response curves; in other words, their effect increases with increasing doses over a broad dosage

range. Partial agonists and agonist-antagonists tend to have ceiling effects; that is, they do not have the

broad dosage range of drugs such as morphine, methadone, hydromorphone, and other "strong" opioids.

This fact mediates against the use of partial agonists and agonist-antagonists in cancer patients who have

chronic pain that may increase as the disease progresses. Three major factors that should be considered

when a drug is selected for clinical use are (1) relative affinities for the different opioid receptor types, (2)

pharmacokinetic characteristics that influence onset and duration of action, and (3) whether the opioids are

strong or weak. For treatment of cancer pain, drugs with long durations of action are

preferable.(ABSTRACT TRUNCATED AT 250 WORDS) [References: 11]

SO - American Journal of Hospital Pharmacy 1990;47:S7-1

UI - 000128

AU - McKinney MW

AU - Londeen TF

AU - Turner SP

AU - Levitt SR

TI - Chronic TM disorder and non-TM disorder pain: a comparison of behavioral and psychological


AB - The purpose of this paper is to determine whether patients with chronic temporomandibular disorder

(TMD) pain manifest behavioral, experimental, and psychological characteristics similar to patients with

other chronic pain illnesses. The Chronic Pain Battery (CPB), a multidimensional assessment tool for chronic

pain patients, was used to compare several important variables between 78 TM disorder (TMD) patients and

98 non-TMD chronic pain patients. The study found that chronic TMD patients had lower "usual" pain

intensity and suffering levels, fewer vegetative symptoms associated with depression, higher pain tolerance,

less impairment of activity, more hope about treatment outcome, lower health care system utilization, but

higher reported stress levels than non-TMD chronic pain patients. The two groups manifested no significant

differences in use of narcotics, sedatives, and sleeping pills; levels of depression, anxiety, somatization,

hostility, or psychoticism; illness behavior reinforcement in their social surroundings; or ratings of problems

with work, family, self-esteem, or suicidal impulses. These findings suggest that chronic TMD pain patients

(with a symptom duration of over six months) are behaviorally and psychologically similar to non-TMD

chronic pain patients, but that they differ in their perceptions of their disorder, rendering them less

handicapped by their problems. Psychological, social, and behavioral treatment methods useful for treating

chronic pain syndrome may thus also be applied along with dental therapy for optimal treatment of TMD

associated with chronic pain

SO - Cranio 1990;8:40-4

UI - 000130

AU - Morawetz RF

AU - Schreithofer D

AU - Bostjancic G

AU - Walter MH

AU - Namestnik E

AU - Benzer H

TI - [The multidisciplinary outpatient pain clinic in relation to anesthesia. An important task for the

anesthesiologist]. [Review] [German]

AB - Anesthesiologists have always played a leading role in research into pain and its treatment. Their

efforts, however, have been focused on acute or postoperative pain problems. It was the American

anesthesiologist John J. Bonica who fought for an increased interest in chronic pain. The establishment of

the first Multidisciplinary Pain Center at the University of Washington in Seattle, the foundation of the

International Association for the Study of Pain (IASP) and Melzack and Wall's now 25 year old gate control

theory were the driving forces behind rapid developments in research and treatment in the area of chronic

pain. The realization that chronic pain was the most frequent cause of disability in the United States also

gave an impetus for new efforts in treatment. The classic anesthesiological topics, such as operative

anesthesia emergency medicine and intensive care, have been extended to include acute pain services and

chronic pain treatment facilities. This reflects the understanding that anesthesiological knowledge and

techniques can be valuable to patients in severe acute pain and those in lingering long-term chronic pain

phases. Anesthesiologists are skilled in the use of opioid narcotics and in the administration of strong

analgesics. Many severe pain problems can be solved by correct use of the analgesic regimen. Special ways

of administering narcotic analgesics, such as epidural infusion or patient-controlled analgesia, have already

alleviated the pain problems of many patients. Anesthesiological techniques are also crucial in diagnosis.

Sequential differential blockade and simple nerve blocks can be helpful in the diagnosis and classification of

the pain problems. Anesthesiological contributions to a chronic pain service are not restricted to medical

interventions. Organizational skills are also needed for efficient running of multidisciplinary pain treatment

facilities. Clinical practice in surgical anesthesia means that anesthesiologists are experienced in

interdisciplinary work and familiar with the advantages and dangers of team work. Despite international

acceptance of the multidisciplinary approach to chronic pain, there is still a lack of appropriate facilities in

the German-speaking countries, and we consider it important that anesthesiologists commit themselves to

increasing general awareness of what is needed. [References: 45]

SO - Anaesthesist 1990;39:456-46

UI - 000129

AU - Osipova NA

AU - Novikov GA

AU - Ziai GR

AU - Mel'nikova ZL

TI - [Tramal in the treatment of acute and chronic pain syndromes in cancer patients]. [Russian]

AB - The study of 65 cancer patients has demonstrated the advantages and disadvantages of tramal as an

agent used for the relief of acute and chronic pain syndrome. In 18 patients tramal was used in postoperative

analgesia, in 17 patients it was used for the treatment of chronic pain syndrome. It has been shown that in

the postoperative period tramal has no noticeable advantages over promedol. However, tramal had definite

advantages over other opiate agonists when used for the treatment of chronic pain syndrome in incurable

cancer patients. Thus, the data obtained show that tramal, a synthetic analgesic of a new generation, has no

dangerous side effects, is effective in a convenient, non-invasive drug form, interacts well with non-narcotic

and supplementary agents and causes no clinical signs of drug tolerance or addiction in prolonged


SO - Anesteziologiya i Reanimatologiya 1990;:55-5

UI - 000144

AU - Payne R

TI - Medication-induced performance deficits: analgesics and narcotics

AB - Pain is the most common medical complaint, and analgesic drugs are often used for its management.

Seven out of 10 Americans took nonprescription pain relievers in the last year. Analgesics are classified as

nonnarcotics (acetaminophen, aspirin, and nonsteroidal anti-inflammatory drugs), narcotics (which include

the morphine-like drugs), and analgesic adjuvants (a heterogeneous group of drugs, including antihistamines,

phenothiazines, anticonvulsants, calcium channel blockers, and tricyclic antidepressants), which may have

intrinsic analgesic efficacy for specific pain syndromes or may be used as co-analgesics in combination with

the traditional nonnarcotic and narcotic agents. Although these agents can be used safely most of the time by

patients with acute or chronic pain, all classes of analgesics may impair cardiovascular and neuropsychiatric

functioning, which may influence job performance in specific instances

SO - Journal of Occupational Medicine 1990;32:362-36

UI - 000137

AU - Portenoy RK

TI - Chronic opioid therapy in nonmalignant pain. [Review]

AB - This review draws on data obtained in the cancer pain, nonmalignant pain, and addict populations to

examine critically the major issues raised by the use of chronic opioid therapy in nonmalignant pain. The

available evidence suggests that there is probably a selected subpopulation of patients with chronic

nonmalignant pain who may obtain sustained partial analgesia without the development of toxicity or the

psychologic and behavioral characteristics of addiction. Future discussions of this approach must adequately

define the terminology of addiction and strive to distinguish medical considerations from the societal and

regulatory influences that may affect prescribing behavior. Those who treat patients with chronic pain must

actively participate in these discussions lest decisions with enormous impact on patient care be made solely

by those whose primary responsibility is the elimination of substance abuse. [References: 114]

SO - Journal of Pain & Symptom Management 1990;5:S46-S62

UI - 000208

AU - Portenoy RK

AU - Foley KM

AU - Inturrisi CE

TI - The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses

derived from studies of opioid infusions [see comments]

SO - (Unknown Journal!) 1990;:

UI - 000140

AU - Portenoy RK

AU - Hagen NA

TI - Breakthrough pain: definition, prevalence and characteristics [see comments]

AB - In the cancer population, the term breakthrough pain typically refers to a transitory flare of pain in the

setting of chronic pain managed with opioid drugs. The prevalence and characteristics of this phenomenon

have not been defined, and its impact on patient care is unknown. We developed operational definitions for

breakthrough pain and its major characteristics, and applied these in a prospective survey of patients with

cancer pain. Data were collected during a 3 month period from consecutive patients who reported moderate

pain or less for more than 12 h daily and stable opioid dosing for a minimum of 2 consecutive days. Of 63

patients surveyed, 41 (64%) reported breakthrough pain, transient flares of severe or excruciating pain.

Fifty-one different pains were described (median 4 pains/day; range 1-3600). Pain characteristics were

extremely varied. Twenty-two (43%) pains were paroxysmal in onset; the remainder were more gradual. The

duration varied from seconds to hours (median/range: 30 min/1-240 min), and 21 (41%) were both

paroxysmal and brief (lancinating pain). Fifteen (29%) of the pains were related to the fixed opioid dose,

occurring solely at the end of the dosing interval. Twenty-eight (55%) of the pains were precipitated; of

these, 22 were caused by an action of the patient (incident pain), and 6 were associated with a non-volitional

precipitant, such as flatulence. The pathophysiology of the pain was believed to be somatic in 17 (33%),

visceral in 10 (20%), neuropathic in 14 (27%), and mixed in 10 (20%). Pain was related to the tumor in 42

(82%), the effects of therapy in 7 (14%), and neither in 2 (4%). Diverse interventions were employed to

manage these pains, with variable efficacy. These data clarify the spectrum of breakthrough pains and

indicate their importance in cancer pain management

SO - Pain 1990;41:273-28

UI - 000199

AU - Portenoy RK

TI - The management of cancer pain

AB - AB - [No Abstract Available] AD - Department of Neurology AD -Memorial Sloan-Kettering Cancer

Center AD - New York AD - NY 10021 UI - 90151022

SO - Compr Ther 1990;16:53-6

UI - 000202

AU - Portenoy RK

TI - Chronic opioid therapy in nonmalignant pain

AB - AB - This review draws on data obtained in the cancer pain, nonmalignant pain, and addict

populations to examine critically the major issues raised by the use of chronic opioid therapy in nonmalignant

pain. The available evidence suggests that there is probably a selected subpopulation of patients with chronic

nonmalignant pain who may obtain sustained partial analgesia without the development of toxicity or the

psychologic and behavioral characteristics of addiction. Future discussions of this approach must adequately

define the terminology of addiction and strive to distinguish medical considerations from the societal and

regulatory influences that may affect prescribing behavior. Those who treat patients with chronic pain must

actively participate in these discussions lest decisions with enormous impact on patient care be made solely

by those whose primary responsibility is the elimination of substance abuse UI -90217697

SO - J Pain Symptom Manage 1990;5:S46-S6

UI - 000132

AU - Sagen J

AU - Wang H

AU - Pappas GD

TI - Adrenal medullary implants in the rat spinal cord reduce nociception in a chronic pain model

AB - Previous work in this laboratory has indicated that the transplantation of adrenal medullary tissue into

the subarachnoid space of the rat spinal cord can reduce pain sensitivity to acute noxious stimuli, particularly

following stimulation by nicotine. This most likely results from the stimulated release of opioid peptides and

catecholamines from the transplanted chromaffin cells. However, chronic pain models may more closely

resemble human clinical pain, and the arthritic rat model has been used for screening potential therapeutic

strategies. The purpose of the present study was to assess the potential for adrenal medullary tissue

implanted into the spinal subarachnoid space to alleviate chronic pain. Adrenal medullary tissue was

implanted into adjuvant-induced arthritic rats, and changes in body weight and vocalization responses were

monitored over the 10 week course of the disease. Results indicate that the severe weight reduction

normally associated with this inflammatory arthritis was attenuated by adrenal medullary, but not control,

implants. In addition, vocalizations were reduced in animals implanted with adrenal medullary, but not

control tissue following nicotine stimulation. This reduction was blocked by the opiate antagonist, naloxone,

and partially attenuated by the alpha-adrenergic antagonist, phentolamine. Together, these results suggest

that the transplantation of adrenal medullary tissue into the subarachnoid space of the spinal cord may

provide a local source of opioid peptides and catecholamines for the reduction of chronic pain

SO - Pain 1990;42:69-7

UI - 000126

AU - Tom CM

AU - Arias LM

AU - Barolat G

TI - Spinal opiate administration: a case of catheter misplacement

AB - Continuous spinal opiate administration via permanently implantable drug delivery devices has been

proven to provide profound analgesia for chronic pain conditions. We present a case in which the catheter of

an implantable subarachnoid device was misplaced into the subdural/extra-arachnoid space despite the free

flow of cerebrospinal fluid. This was verified by x-ray dye studies. It is postulated that this misplacement of

the catheter likely occurred as a result of recent lumbar punctures the patient had undergone. Extravasation

of cerebrospinal fluid created a false space and contributed to the misplacement and ultimate failure of the

device to provide analgesia

SO - Clinical Journal of Pain 1990;6:60-6

UI - 000072

AU - Ansuategui M

AU - Naharro L

AU - Feria M

TI - Noradrenergic and opioidergic influences on the antinociceptive effect of clomipramine in the

formalin test in rats

AB - Although tricyclic antidepressants are especially useful in the treatment of chronic pain conditions,

most of the work about its mechanism of action has been made on acute pain tests. The present study was

aimed at studying the role played by noradrenergic and opioidergic influences on the antinociceptive activity

of subchronically administered clomipramine in the formalin test (a tonic pain model) in rats. Clomipramine

produced antinociception after 7 days, administration (2.5 mg/kg/day), an effect equivalent to that obtained

by acute morphine (5 mg/kg). The antinociceptive effect of clomipramine was inhibited by the following:

nonspecific blocking of alpha 1- and alpha 2-adrenoceptors by phentolamine, specific blocking of alpha 1-

adrenoceptors by prazosin; stimulation of alpha 2 receptors by clonidine; and blocking of the opioid

receptors by naloxone. Blocking the alpha 2-receptors with yohimbine did not antagonize the effect of

clomipramine. These results suggest that clomipramine produces antinociception in this test, partly via the

participation of the endogenous opioid system and partly by further activating or potentiating previously

activated noradrenergic pathways which are involved in the control of pain information

SO - Psychopharmacology 1989;98:93-9

UI - 000069

AU - Arnold C

TI - Intraspinal analgesia: a new route for an old drug

AB - Chronic pain control is a pressing world health problem. Despite the magnitude of this health issue,

health care professionals receive little formal training in pain management, hence attempts to deal with

chronically suffering patients may be futile. A new intervention, the infusion of low-dose spinal opiates via a

totally implanted continuous flow pump, is providing a new approach to pain control and offering a desirable

alternative to the need for escalating systemic narcotics and neuroablative procedures. A brief overview of

the anatomy and physiology of the pain mechanism will be discussed as well as rationale for the use of

continuous infusion of spinal opiates. Nursing interventions for the patient receiving intraspinal analgesia will

also be discussed

SO - Journal of Neuroscience Nursing 1989;21:30-3

UI - 000025

AU - Berde C

AU - Sethna NF

AU - Masek B

AU - Fosburg M

TI - Pediatric pain clinics: Recommendations for their development

AB - IN: Children's Hospital Dept of Anesthesia, Boston, MA, US LA: English AB: Adult clinics serve as

models for pediatric pain programs, although adult and pediatric pain syndromes differ substantially. The

paper describes attributes of a pediatric acute pain management program, including involvement of clinicians

with both medical and psychosocial orientations, a cognitive-behavioral program, and rational use of

systemic opioids. Chronic cancer pain management is discussed, and psychological and pharmacological

approaches to chronic pain not due to cancer are considered. (PsycLIT Database Copyright 1991 American

Psychological Assn, all rights reserved) KP: model of pain management program using medical &

psychosocial orientation & cognitive behavioral & opioid treatment; children AN: 78-07772

SO - Pediatrician 1989;16:94-10

UI - 000070

AU - Boisaubin EV

TI - The assessment and treatment of pain in the emergency room. [Review]

AB - A broad spectrum of painful conditions presents to the modern emergency center (EC). The three

most common categories are acute, self-limited disorders; chronic medical or surgical syndromes with acute

exacerbation; and psychic pain syndromes in which the etiology cannot be easily ascertained. Many factors

may differentiate pain from suffering, and physicians should educate patients not only about the nature of

their condition and its prognosis, but also about anticipated discomfort. Clinical concerns in the EC include

physicians' tendency to undertreat or even ignore pain, the need for appropriate but flexible dosage

schedules, and physicians' concern about masking important signs and symptoms. Nonsteroidal anti-

inflammatory drugs (NSAIDs) are currently the safest and most effective group of oral analgesics. Important

factors for drug selection include efficacy, dosage, lack of side effects, and cost. Two special groups of

patients, those with psychic pain syndromes and those with drug-seeking behavior, can create problems for

the physician. Patients with chronic pain syndromes need special follow-up but do not benefit from

additional analgesic drug therapy. Patients who seek and abuse drugs can be difficult to identify, may have

true underlying medical pathology, and should not be given narcotic prescriptions. [References: 15]

SO - Clinical Journal of Pain 1989;5 Suppl 2:S19-24; discussion S24-

UI - 000076

AU - Busch EH

AU - Atchison SR

TI - Steroid celiac plexus block for chronic pancreatitis: results in 16 cases

AB - Sixteen cases in which celiac plexus block with depot steroid was used to treat chronic pancreatitis

pain were reviewed. Only 4 of 16 patients reported pain relief with the procedure. Of the 12 patients who

did not obtain relief, narcotic dependence was present in 11 of 12. No patients in the "relief" group were

narcotic dependent. Prior pancreatic surgery was present in 9 of the 12 patients without relief and in 1 of 4

patients with relief. It is postulated that refractory chronic pancreatitis pain may be an extreme form of what

has been termed "abnormal illness behavior." Furthermore, these results underscore the poor results

experienced using neural blockade for the relief of chronic pain when narcotic dependence is present

SO - Journal of Clinical Anesthesia 1989;1:431-43

UI - 000068

AU - Delay-Goyet P

AU - Kayser V

AU - Zajac JM

AU - Guilbaud G

AU - Besson JM

AU - Roques BP

TI - Lack of significant changes in mu, delta opioid binding sites and neutral endopeptidase EC in the brain and spinal cord of arthritic rats

AB - The possible changes in neutral endopeptidase EC ("enkephalinase", NEP), mu and delta

opioid binding sites, were investigated using in vitro quantitative radioautography in various regions of the

central nervous system of the Freund's adjuvant-induced arthritic rat, a model of chronic pain. Enkephalinase

was labeled by a specific tritiated inhibitor, [3H]N-[(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-

oxopropyl]glycine ([3H]HACBO-Gly), while mu and delta opioid binding sites were selectively labelled with

[3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol ([3H]DAGO) and [3H]Tyr-D-Thr-Gly-Phe-Leu-Thr ([3H]DTLFT),

respectively. As compared to controls, no significant modifications were found in NEP, mu or delta binding

sites at both supraspinal and spinal levels of arthritic rats. These results suggest that the enhanced efficiency

of exogenous opioids or endogenous enkephalins, reported to occur in this model of chronic inflammatory

pain, are not directly related to changes in mu and delta opioid binding sites or steady state levels of NEP

SO - Neuropharmacology 1989;28:1341-134

UI - 000071

AU - Ellis JS Jr.

AU - Ramamurthy S

AU - Schoenfeld LS

AU - Hoffman J

AU - Walsh NE

TI - Diagnostic epidural opioid technique

AB - Diagnostic epidural blocks were performed on 27 chronic pain patients sequentially using saline,

fentanyl, and lidocaine solution. The patients were divided into one of four groups based on their response

to the epidural solutions: placebo response group--pain relief with placebo solutions; fentanyl response

group--pain relief with epidural fentanyl; lidocaine response group (LRG)--pain relief with lidocaine but not

fentanyl; and no response group--no pain relief with any of the solutions used. The four groups were

compared on the basis of age, sex, site of pain, duration of pain, narcotic use, pain assessment index, and

workmen's compensation claims. The comparisons resulted in the conclusion that LRG patients had a much

longer average duration of pain than the other groups. On the basis of the information gathered, it was

theorized that, despite their response to epidural lidocaine, LRG patients may actually be a group of operant

pain patients. Their failure to receive analgesia from epidural fentanyl may be a learned response such that

they associate any sensory input from the affected area as painful. If follow-up studies support these

findings, then the diagnostic opioid technique may be a more sensitive tool in diagnosing chronic pain

SO - Clinical Journal of Pain 1989;5:211-21

UI - 000066

AU - Fields HL

TI - Pain modulation: opiates and chronic pain. [Review]

SO - NIDA Research Monograph Series 1989;95:92-10

UI - 000081

AU - Hand CW

AU - Ryan KE

AU - Dutt SK

AU - Moore RA

AU - O'Connor J

AU - Talbot D

AU - McQuay HJ

TI - Radioimmunoassay of buprenorphine in urine: studies in patients and in a drug clinic

AB - A radioimmunoassay kit (DPC buprenorphine double antibody) was evaluated with clinical samples

and samples from a drug clinic. Urine samples were collected over a 2-day period from 5 hospital in-patients

receiving sublingual buprenorphine, 400 to 2000 micrograms/day, for the relief of chronic pain. Samples

were measured before and after enzymatic hydrolysis. Urine buprenorphine concentrations were measurable

at all doses studied (minimum value 5.6 ng/mL) and were greater with larger doses. The increase in

concentration after hydrolysis averaged 49% and was similar for all doses studied. The authors conclude that

the method has extensive cross-reactivity with glucuronides of buprenorphine and its metabolites and that

samples may be analyzed without prior hydrolysis. The prevalence of buprenorphine use in 97 patients

attending a drug clinic was also studied. Sixty (62%) had measurable urinary buprenorphine concentrations

of 1 ng/mL or more by direct assay. The buprenorphine users were significantly younger and reported

significantly greater use of opiates than nonusers

SO - Journal of Analytical Toxicology 1989;13:100-10

UI - 000067

AU - Herz A

AU - Millan MJ

AU - Stein C

TI - Arthritic inflammation in rats as a model of chronic pain: role of opioid systems. [Review]

SO - NIDA Research Monograph Series 1989;95:110-11

UI - 000077

AU - Lipman JJ

AU - Blumenkopf B

TI - Comparison of subjective and objective analgesic effects of intravenous and intrathecal

morphine in chronic pain patients by heat beam dolorimetry

AB - The pain tolerance latencies of 10 chronic pain patients were evaluated by heat beam dolorimetry

(stimulus intensity 15.33 mW.cm-2.sec-1) prior to and following administration of morphine by intrathecal

(n = 5) or intravenous (n = 5) routes. Patients not undergoing opiate withdrawal evinced increased baseline

pain tolerance latencies prior to drug administration compared with normal volunteers. Two patients

undergoing the opiate withdrawal syndrome at the time of test experienced reduced pain tolerance latencies

compared with normal volunteers, most probably corresponding to the hyperesthesia symptom of the

syndrome. Intravenous morphine infusion (30 mg) induced a time-dependent increase in cutaneous pain

tolerance with peak effect occurring 1-2 h after administration. This persisted for up to 4 h and thereafter

declined. The time course of subjective pain self-report by visual pain analog scale (VPAS) measurements

corresponded to the time course of increasing cutaneous pain tolerance latency assessed by dolorimetry.

Pain self-reports following intrathecal morphine infusion (2.25 or 1 mg) followed a similar though slower

onset to that reported by patients receiving intravenous morphine and was of lesser degree. In contrast, heat

beam dolorimetric evidence of increased cutaneous pain tolerance (which was of lesser degree than

following i.v. morphine) did not reach its maximum during the 4 h measuring period. A dissociation was

noted therefore between the self-reported relief of endogenous pain and dolorimetrically measured

cutaneous analgesia following intrathecal morphine administration. Linear regression correlation analysis

characterized this phenomenon as a positive correlation between cutaneous pain tolerance and pain relief

self-report following intravenous morphine infusion and a negative correlation following intrathecal

administration. We propose that the phenomenon may be due to intrathecal morphine acting via two

separate compartments: one spinal and one supraspinal.(ABSTRACT TRUNCATED AT 250 WORDS)

SO - Pain 1989;39:249-25

UI - 000082

AU - Lombard MC

AU - Besson JM

TI - Electrophysiological evidence for a tonic activity of the spinal cord intrinsic opioid systems in a

chronic pain model

AB - The aim of this electrophysiological investigation was to evaluate the activity of the spinal endogenous

opioid systems in a chronic pain model, the arthritic rat. The activity of nociceptive non-specific dorsal horn

neurons (n = 23) were recorded in 23 spinal unanesthetized decerebrated rats. Naloxone (1 mg/kg i.v.)

induced a highly significant increase in the spontaneous firing rate of these neurons. This observation is in

favor of a tonic activity of spinal opioid endogenous systems in such a disease. In addition, the same dose of

naloxone facilitates the transmission of noxious messages at the spinal level as revealed by the large

enhancement of the responses of these neurons to C-fiber stimulation. These results are in good agreement

with behavioral data showing that such a relatively high dose of naloxone induced well-reproducible

hyperalgesia and with some biochemical observations showing an increase of levels and biosynthesis of

endogenous opioids in the spinal cord of the arthritic rat

SO - Brain Research 1989;477:48-5

UI - 000075

AU - McQuay HJ

TI - Opioids in chronic pain. [Review]

SO - British Journal of Anaesthesia 1989;63:213-226

UI - 000080

AU - Pettine KA

AU - Wedel DJ

AU - Cabanela ME

AU - Weeks JL

TI - The use of epidural bupivacaine following total knee arthroplasty

AB - Pain relief and maximization of knee joint range of motion (ROM) are the two major goals in the

postoperative management of the total knee arthroplasty (TKA) patient. Epidural bupivacaine infusions have

been reported to be safe and effective for pain control in obstetric anesthesia, chronic pain management, and

postoperative pain relief. The purpose of this study was to evaluate the effect of continuous epidural

bupivacaine on postoperative pain and progressive knee ROM as well as to record the incidence of urinary

retention and other side effects or complications. Continuous epidural bupivacaine infusion was found to

provide safe, effective analgesia for TKA patients in the immediate postoperative period. Excellent pain

relief with reduced narcotic requirements was observed in the patients as compared to intramuscular narcotic

analgesia. No complications occurred and serum bupivacaine levels remained well below toxic levels. Short

term clinical orthopaedic outcome was improved, and patient, surgeon, and nurse acceptance of the

technique was excellent

SO - Orthopaedic Review 1989;18:894-901

UI - 000203

AU - Portenoy RK

TI - Use of methylphenidate as an adjuvant to narcotic analgesics in patients with advanced cancer

AB - AB - [No Abstract Available] UI - 89381479

SO - J Pain Symptom Manage 1989;4:suppl 3:2,4-suppl 3:2,4

UI - 000079

AU - Racz GB

AU - McCarron RF

AU - Talboys P

TI - Percutaneous dorsal column stimulator for chronic pain control

AB - This is a retrospective review of 26 patients with chronic intractable pain in which dorsal column

stimulation was used as a salvage procedure. On follow-up of 12 to 42.7 months, 21 of the patients had

diminished narcotic usage. Seventeen patients subjectively rated their pain relief as good to excellent.

Another five patients reported some relief of pain. Two-thirds of the patients reported an increase in their

ability to perform daily activities such as walking, stair climbing, and time spent sitting. There are still many

technical problems that plague this procedure, as evidenced by a very high technical complication rate of

lead migration and lead breakage. Whether or not results diminish over long-term follow-up remains to be


SO - Spine 1989;14:1-4

UI - 000074

AU - Russegger L

TI - Chronic pain conditions--causes, manifestations and neurosurgical treatment possibilities.

[Review] [German]

AB - The relief of chronic pain, which had lost its warning function and had become a disease entity, is one

of the main scopes of the so-called "functional neurosurgery". If it is impossible to eliminate the origin of

chronic pain condition, or if conservative treatment is not effective, this is an indication for a surgical

intervention. "Destructive methods" in pain surgery aim at interrupting the pathway of pain in one of its

three steps (neurons). The decision which method should be used depends on character and localisation of

pain and requires well-founded experience by the surgeon. "Non-destructive" operations include stimulation

methods of several CNS areas as well as implantation of drug reservoirs which conceded a continuous

release of morphine or morphine derivatives to the opiate receptors of the spinal cord. The paper evaluates

the most common surgical procedures in pain relief concerning technique, indication and efficacy and gives a

survey on the pathophysiological background of chronic pain. [References: 70]

SO - Fortschritte der Neurologie-Psychiatrie 1989;57:319-327

UI - 000078

AU - Swanson G

AU - Smith J

AU - Bulich R

AU - New P

AU - Shiffman R

TI - Patient-controlled analgesia for chronic cancer pain in the ambulatory setting: a report of 117


AB - Patient-controlled analgesia (PCA) represents a drug-delivery system in which patients self-administer

predetermined doses of opiate analgesics. We have taken advantage of recent advances in pump technology

and developed a system in which patients with severe pain received a continuous narcotic infusion, along

with the capability of PCA bolus for breakthrough pain. All patients were experiencing chronic pain related

to cancer and were unable to obtain adequate pain control with either intermittent parenteral, oral, or rectal

narcotics. Sixty-nine percent of patients were treated in the home setting, and the majority received

morphine sulfate subcutaneously (SQ). Admixture stability studies using high-pressure liquid

chromatography (HPLC) showed that dexamethasone, metoclopramide, and haloperidol could be added to

the morphine solutions and remain stable for 1 week at room temperature. Of 117 patients entered, 95%

received excellent pain control, and side effects were rare, consisting of subcutaneous needle site infection

and respiratory depression. Progressive pain due to either advancing disease or development of drug

tolerance could be controlled by increasing opiate infusion rates. We conclude that (1) continuous infusion

opiate with PCA bolus capability can be initiated and administered safely in the home setting; (2) patients

with pain related to malignancy can be managed well with this system; and (3) pain control programs can be

designed, implemented, and evaluated in the private practice setting

SO - Journal of Clinical Oncology 1989;7:1903-1908

UI - 000217

AU - Vaccarino AL

AU - Tasker RA

AU - Melzack R

TI - Analgesia produced by normal doses of opioid antagonists alone and in combination with


AB - AB - In a recent study [30] it was reported that naloxone, at doses normally employed for opioid

antagonism, produced a dose-dependent analgesia in BALB/c mice in the formalin test. We report here that

another opioid antagonists, naltrexone, also produces analgesia under these conditions. Female BALB/c

mice were injected subcutaneously with naltrexone (0.01-1.0 mg/kg) or saline alone and tested for analgesia

using the formalin test. Naltrexone produced a statistically significant dose-dependent analgesia, with an

ED50 of 0.05 mg/kg and almost total analgesia at doses of 0.1 mg/kg or greater. To determine the

relationship between naloxone analgesia and better documented forms of opioid analgesia, BALB/c mice

were injected with naloxone or saline following the administration of a pre-determined ED50 for morphine

and tested for analgesia using the tail-flick and formalin tests. Naloxone antagonized morphine analgesia in

the tail-flick test at both doses used (0.3 and 10 mg/kg). In the formalin test, however, naloxone attenuated

morphine analgesia at the lower doses (0.1 and 0.3 mg/kg) and potentiated morphine analgesia at the highest

dose (10 mg/kg). The implications of this finding are discussed AD - Department of Psychology AD -McGill

University AD - Montreal AD - Que AD - Canada UI - 89144631

SO - Pain 1989;36:103-109

UI - 000251

AU - Weissman DE

AU - Haddox JD

TI - Opioid pseudoaddiction--an iatrogenic syndrome

AB - AB - A case is presented of a 17-year-old with leukemia, pneumonia and chest-wall pain. Inadequate

treatment of the patient's pain led to behavioral changes similar to those seen with idiopathic opioid

psychologic dependence (addiction). The term pseudoaddiction is introduced to describe the iatrogenic

syndrome of abnormal behavior developing as a direct consequence of inadequate pain management. The

natural history of pseudoaddiction includes progression through 3 characteristic phases including: (1)

inadequate prescription of analgesics to meet the primary pain stimulus, (2) escalation of analgesic demands

by the patient associated with behavioral changes to convince others of the pain's severity, and (3) a crisis of

mistrust between the patient and the health care team. Treatment strategies include establishing trust

between the patient and the health care team and providing appropriate and timely analgesics to control the

patient's level of pain AD - Division of Hematology/Oncology AD - Medical College of Wisconsin AD -

Milwaukee 53226 UI - 89220105

SO - Pain 1989;36:363-366

UI - 000073

AU - Yaster M

AU - Deshpande JK

AU - Maxwell LG

TI - The pharmacologic management of pain in children. [Review]

AB - We have attempted to dispel many of the myths and misconceptions surrounding the use of narcotic

analgesics in the treatment of childhood pain. Our hope is that an improved understanding and application of

effective and safe therapies will minimize the suffering of the child with acute or chronic pain. [References:


SO - Comprehensive Therapy 1989;15:14-26

UI - 000091

AU - Amadio P Jr.

AU - Cummings DM

AU - Amadio PB

TI - A framework for management of chronic pain

AB - The management of chronic pain requires a physician who is motivated to provide care for patients

with this difficult problem. A thorough search must be made to determine the cause of the pain, the extent of

psychiatric overlay, the importance of the pain to the patient (litigation, secondary gain), the extent of illness

behavior and the response to previous therapy. The physician must be part of the treatment rather than part

of the problem. Narcotic analgesics should be avoided except in patients with cancer pain or terminal illness

SO - American Family Physician 1988;38:155-160

UI - 000090

AU - Arner S

AU - Meyerson BA

TI - Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain [see comments]

AB - The aim of the present study has been to assess the responsiveness of various types of chronic pain to

opioids given i.v. and tested against placebo in a double-blind, randomized fashion. Pain classified as primary

nociceptive was effectively alleviated (P greater than 0.001) while neuropathic deafferentation pain was not

significantly influenced by morphine or equivalent doses of other opioids. Also 'idiopathic' pain, defined as

chronic pain with no or little demonstrable pathology, failed to respond. The results were not related to

whether the patients were regular users of narcotic analgesics or not. The outcome of our double-blind

opioid test has proved useful to justify a continued, or discontinued, use of narcotic medication in individual

patients. It may also support the indication and choice of invasive stimulation procedures (spinal cord or

brain). The results of the study illustrate the misconception of chronic pain as an entity and highlight the

importance of recognizing different neurobiological mechanisms and differences in responsiveness to

analgesic drugs as well as to non-pharmacological modes of treatment. The opioid test has thus become a

valuable tool in pain analysis and helpful as a guide for further treatment

SO - Pain 1988;33:11-23

UI - 000084

AU - Barni S

AU - Lissoni P

AU - Rovelli F

AU - Crispino S

AU - Paolorossi F

AU - Esposti D

AU - Esposti G

AU - Fraschini F

AU - Tancini G

TI - Alteration of opioid peptide circadian rhythm in cancer patients

AB - Endogenous opioid peptides have been seen to play a role in regulating immunity and tumor growth.

This study was carried out to investigate opioid activity in human cancer. We evaluated by

radioimmunoassay beta-endorphin plasma levels on blood samples collected at 9.00 a.m. from 121 cancer

patients and 42 healthy subjects. In 22 cancer patients and in 12 controls, beta-endorphin circadian rhythm

was also investigated. Finally, in 14 cancer patients and in 10 controls GH, PRL, FSH, LH and cortisol

serum levels were measured after the administration of a metenkephalin analogue, FK 33-824 (0.3 mg i.v.).

No significant differences were seen in beta-endorphin mean levels between cancer patients and normal

subjects. Moreover, no differences were found between patients with or without metastases, nor between

those with or without chronic pain. beta-Endorphin circadian rhythm appeared to be altered in 16/22 cancer

patients, and anomalous hormonal responses to FK 33-824 were seen in 13/14 patients. This study shows an

altered opioid activity in human neoplasms, whose clinical significance remains to be determined

SO - Tumori 1988;74:357-360

UI - 000089

AU - Beaver WT

TI - Impact of non-narcotic oral analgesics on pain management. [Review]

AB - Of the four categories of oral analgesics, three have been available since the 19th century. Although

adequate doses of the more potent oral opioids such as morphine and methadone are effective even in severe

pain, the commonly used "weak" narcotics such as codeine and propoxyphene are no more effective than

usual doses of aspirin or acetaminophen. Furthermore, the opioids produce gastrointestinal and central

nervous system adverse effects, and, during long-term administration, tolerance may develop and there is a

risk of drug dependence. Aspirin and acetaminophen are the traditional agents of choice for oral analgesic

therapy; until 10 years ago, there were no single-entity, oral analgesics--with the exception of large doses of

oral narcotics--that were more effective than usual doses of aspirin or acetaminophen. However, there is a

ceiling on the analgesic effect attainable with safe doses of these drugs, which may in part be overcome

through the use of the third category of oral analgesics, combinations of aspirin or acetaminophen with oral

opioids. The fourth category of oral analgesics constitutes the most important recent development in pain

management with analgesic drugs: the newer peripherally acting, nonsteroidal anti-inflammatory analgesics,

some of which are clearly more efficacious than aspirin or acetaminophen and compare favorably not only

with full doses of narcotic combination products but even, in some cases, with strong injectable opioids. On

repeated dosing, some nonsteroidal anti-inflammatory drugs are better tolerated than aspirin and some have

a much longer duration of analgesic effect than aspirin or acetaminophen. Further study is needed to

compare nonsteroidal anti-inflammatory drugs among themselves and to determine their value in chronic

pain and in combination therapy. [References: 37]

SO - American Journal of Medicine 1988;84:3-15

UI - 000086

AU - Deyo RA

AU - Bass JE

AU - Walsh NE

AU - Schoenfeld LS

AU - Ramamurthy S

TI - Prognostic variability among chronic pain patients: implications for study design,

interpretation, and reporting

AB - Chronic pain patients share many characteristics, but there is important prognostic variability among

them. By selecting for certain characteristics, different recruitment methods and entry criteria for clinical or

research programs may influence the likelihood of success regardless of treatment efficacy. This was

demonstrated when subjects (n = 55) were recruited through lay publicity for a clinical trial of therapy for

chronic back pain. In comparison to routine pain clinic patients (n=61), subjects in the clinical trial were

better educated, were more often employed, had more favorable personality profiles, and were less likely to

have had surgery or narcotic use (all p less than 0.004). Pain relief was significantly better for clinical trial

subjects, apparently due to baseline prognostic differences rather than uniquely efficacious therapy. We

conclude that chronic pain patients vary in prognostically important ways; that recruitment methods and

criteria strongly influence these characteristics; and that greater attention to these details is needed when

interpreting and reporting clinical research

SO - Archives of Physical Medicine & Rehabilitation 1988;69:174-178

UI - 000085

AU - Gottlieb H

AU - Alperson BL

AU - Schwartz AH

AU - Beck C

AU - Kee S

TI - Self-management for medication reduction in chronic low back pain

AB - It has been demonstrated that pain relief is seldom produced by medication or surgical methods where

there is evidence of emotional disturbance, as indicated by the MMPI. A program that attempts to engender

a high level of patient responsibility in a population of chronic low back pain patients is described. Self-

managed reduction of drug dependence is a major component of this program. The data indicate that the

program produces a significant reduction in dependence on opiates, derivatives, synthetic opiates, hypnotics,

sedatives, tranquilizers, and analgesics. Follow-up data (with attrition controlled) at six months and 12

months postdischarge do not provide any evidence for deterioration (ie, return to pretreatment levels of drug

dependence). Thus, it appears that the programmatic impact is stable over at least a 12-month period

postdischarge. Implications of these findings for the low back pain population, as well as other chronic pain

populations, are discussed

SO - Archives of Physical Medicine & Rehabilitation 1988;69:442-448

UI - 000240

AU - Hartman B

AU - Miyada DS

AU - Pirkle H

AU - Sedgwick P

AU - Cravey RH

AU - Tennant FS Jr.

AU - Wolen RL

TI - Serum propoxyphene concentrations in a cohort of opiate addicts on long-term propoxyphene

maintenance therapy. Evidence for drug tolerance in humans

AB - AB - Propoxyphene, norpropoxyphene, and cyclic dinorpropoxyphene concentrations in the sera of

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eight opiate addicts were measured by gas chromatography. The addicts were enrolled in a propoxyphene

maintenance program and had received 800-1600 mg of propoxyphene napsylate daily for 13-50 months.

Serum propoxyphene and norpropoxyphene ranged from 127 to 1070 ng/mL and 814 to 2638 ng/mL,

respectively, and their ratio ranged from 0.1 to 0.4. A roughly linear dose-to-serum-concentration

relationship was found for serum propoxyphene and norpropoxyphene in the cohort. Cyclic

dinorpropoxyphene was detected in three of the subjects' sera. Because tolerance to propoxyphene occurs,

knowledge of prior drug exposure is necessary to determine whether an elevated propoxyphene or

norpropoxyphene concentration is toxic to patients or decedents with apparent propoxyphene overdose.

Serum norpropoxyphene concentration exceeds that of propoxyphene following chronic propoxyphene use.

Measurable cyclic dinorpropoxyphene implies chronic propoxyphene use but its absence does not exclude

chronic use AD - Department of Pathology AD - Los Angeles County High Desert Hospital AD - Lancaster

AD -CA UI - 88173501

SO - J Anal Toxicol 1988;12:25-29

UI - 000027

AU - Larson AA

TI - Desensitization to intrathecal substance P in mice: Possible involvement of opioids

AB - IN: U Minnesota, St Paul, US LA: English AB: Intrathecal injection of substance P (SP) in mice

resulted in a behavioral syndrome characterized by caudally directed biting and scratching. Repeated

injections of SP resulted in development of tachyphylaxis (TP) to this SP-induced behavioral phenomenon.

Naloxone combined with SP blocked TP to SP in naive Ss. Fluoxetine or phentolamine blocked TP to SP.

(PsycLIT Database Copyright 1989 American Psychological Assn, all rights reserved) KP: chronic pain;

caudally directed biting & scratching induced by intrathecal substance P with vs without naloxone vs

fluoxetine vs phentolamine; mice AN: 76-04403

SO - Pain 1988;32:367-374

UI - 000093

AU - Mogensen T

AU - Scott NB

AU - Lund C

AU - Bigler D

AU - Hjortso NC

AU - Kehlet H

TI - The roles of acute and chronic pain in regression of sensory analgesia during continuous

epidural bupivacaine infusion

AB - The purpose of this study was to investigate whether regression of sensory analgesia during constant

epidural bupivacaine infusion was different in postoperative patients with acute pain than in patients with

chronic nonsurgical pain. Sensory levels of analgesia (to pinprick) and pain (on a five-point scale) were

assessed hourly for 16 hours during continuous epidural infusion of 0.5% plain bupivacaine (8 ml/hr) in 12

patients with chronic nonsurgical pain and in 30 patients after major abdominal surgery performed under

combined bupivacaine and halothane--N2O general anesthesia. No opiates were given. If sensory analgesia

decreased more than five segments from the initial level or if the pain score reached 2 (moderate pain), the

patient was removed from the study. Initial levels of sensory analgesia after loading doses of 21.8 +/- 0.5

and 19.3 +/- 0.8 ml bupivacaine 0.5% were similar (T3.8 +/- 0.3 and T3.8 +/- 0.5) in the surgical and

chronic pain patients, respectively (mean +/- SEM). Of the surgical patients, only 4 of the 30 (13%)

maintained the initial level of sensory analgesia, and a pain score below 2 throughout the study compared

with 7 of the 12 patients with chronic pain (58%) (P less than 0.01). Mean duration of sensory blockade was

significantly longer (P less than 0.005) in the patients with chronic pain than in surgical patients (13.1 +/- 1.2

and 8.5 +/- 0.7 hours, respectively). Thus, surgical injury hastens regression of sensory analgesia during

continuous epidural bupivacaine infusion. The underlying mechanism remains to be determined

SO - Anesthesia & Analgesia 1988;67:737-740

UI - 000094

AU - Moossy JJ

AU - Nashold BS Jr.

TI - Dorsal root entry zone lesions for conus medullaris root avulsions

AB - We have found dorsal root entry zone (DREZ) lesions to be an effective treatment of chronic

deafferentation pain in patients who have had avulsions of the dorsal rootlets from the spinal cord. Eight

patients were operated in whom chronic pain of the lower extremity resulted from dorsal root avulsions from

the conus medullaris. In 7 of the 8 patients, the mechanism of injury was a motor vehicle accident; all 7

sustained severe pelvic trauma. Seven of the 8 patients remained pain-free, off all narcotics, with an average

follow-up of 33 months. All patients had DREZ lesions of the conus performed by radiofrequency


SO - Applied Neurophysiology 1988;51:198-205

UI - 000187

AU - Portenoy RK

TI - Practical aspects of pain control in the patient with cancer

AB - Cancer-related pain can be well controlled in most patients. With prolonged survival and cure now

possible with many tumors, pain management becomes a compelling issue for the quality of the patient's

remaining life. In advanced stages of disease, analgesia is an imperative for both the patient and family; it

provides the patient the opportunity for a dignified and comfortable death and lifts from the family the added

burden of anger and despair that is so often associated with uncontrolled pain in a loved one. Astute

assessment, a systematic approach to pharmacologic treatment, and ongoing monitoring of therapy are the

fundamental elements of successful management of pain in most patients

SO - CA Cancer J Clin 1988;38:327-352

UI - 000191

AU - Portenoy RK

TI - Practical aspects of pain control in the patient with cancer

AB - Cancer-related pain can be well controlled in most patients. With prolonged survival and cure now

possible with many tumors, pain management becomes a compelling issue for the quality of the patient's

remaining life. In advanced stages of disease, analgesia is an imperative for both the patient and family; it

provides the patient the opportunity for a dignified and comfortable death and lifts from the family the added

burden of anger and despair that is so often associated with uncontrolled pain in a loved one. Astute

assessment, a systematic approach to pharmacologic treatment, and ongoing monitoring of therapy are the

fundamental elements of successful management of pain in most patients AD - Department of Neurology AD

- Memorial Sloan-Kettering Cancer Center AD - New York AD - New York UI -89027782

SO - CA Cancer J Clin 1988;38:327-352

UI - 000092

AU - Reidenberg MM

AU - Goodman H

AU - Erle H

AU - Gray G

AU - Lorenzo B

AU - Leipzig RM

AU - Meyer BR

AU - Drayer DE

TI - Hydromorphone levels and pain control in patients with severe chronic pain [published erratum

appears in Clin Pharmacol Ther 1991 Mar;49(3):313]

AB - To better understand the use of narcotic analgesics, the hydromorphone concentration was measured

in serum samples from 43 patients with chronic severe pain who were receiving this drug. At the time of

blood sampling, pain intensity, mood, and cognitive performance were assessed. There was large individual

variation in the dose-drug level relationship. Seven patients with bone or soft tissue pain and drug levels of

greater than or equal to 4 ng/ml had good pain control, whereas 10 did not. None of 15 patients with levels

less than 4 ng/ml had pain control, despite drug doses similar to those given patients with higher levels. Thus

60% of the patients without control of their pain had hydromorphone levels below the lowest level that

produced pain control. No patient with pain from nerve infiltration or compression had good pain control,

irrespective of the drug level or dose. Poor mood correlated with high pain intensity and low drug level.

Impaired cognitive performance was not related to drug level. Knowing that there is a low concentration of

narcotic in the blood of a patient with chronic severe pain who is receiving high drug doses and who shows

lack of both efficacy and side effects may reassure health care professionals that further narcotic dosage

escalation is appropriate

SO - Clinical Pharmacology & Therapeutics 1988;44:376-382

UI - 000026

AU - Shippenberg TS

AU - Stein C

AU - Huber A

AU - Millan MJ

TI - Motivational effects of opioids in an animal model of prolonged inflammatory pain: Alteration

in the effects of k- but not of m-receptor agonists

AB - IN: Max-Planck-Inst fur Psychiatrie, Martinsried, Fed Rep Germany LA: English AB: A preference

conditioning procedure was used to examine the motivational effects of opioids in naive male rats and male

rats suffering from prolonged pain associated with Freund's adjuvant (FA)-induced inflammation of a

hindlimb. It was found that the mu- opioid agonist morphine functioned as a reinforcer in naive Ss producing

marked preferences for the drug-paired place. Ss injected with FA 7 days prior to conditioning exhibited a

preference for the morphine place. Administration of the kappa- opioid receptor agonist U-69593 to naive

Ss produced dose-related place aversions. The aversive effect of this kappa-agonist was, however, abolished

in FA-treated Ss. Data suggest that kappa- agonists may be effective therapeutic agents in the management

of chronic pain states. (PsycLIT Database Copyright 1989 American Psychological Assn, all rights reserved)

KP: motivational effects of opioids; male rats; animal model of prolonged inflammatory pain AN: 76-21813

SO - Pain 1988;35:179-186

UI - 000087

AU - Sjostrom S

TI - The relationship between the pharmacokinetics and pharmacodynamics of spinal opioids.

Minireview based on a doctoral thesis. [Review]

AB - Spinal opioids have been used clinically since the late seventies to treat acute, traumatic, obstetric and

chronic pain. In this article the influence of the pharmacokinetics on the dynamics of intrathecal and epidural

opioid administration are discussed with reference to current knowledge. [References: 121]

SO - Upsala Journal of Medical Sciences 1988;93:101-120

UI - 000083

AU - Tonelli L

AU - Setti T

AU - Falasca A

AU - Martignoni E

AU - Torcia E

AU - Calcaterra FM

AU - Merli GA

AU - Facchinetti F

TI - Investigation on cerebrospinal fluid opioids and neurotransmitters related to spinal cord


AB - The purpose of this study was to assess the biochemical mechanisms underlying spinal cord

stimulation (SCS). Seventeen patients with chronic pain were investigated by measuring cerebrospinal fluid

concentrations of endogenous opioids and biogenic amines before and during dorsal column stimulation.

Basal cerebrospinal fluid beta-endorphin levels were below the normal range. No significant change of

norepinephrine, epinephrine, dopamine, beta-endorphin, beta-lipotropin, or adrenocorticotropic hormone

levels were found after SCS. A 50% increase of cerebrospinal beta-endorphin and beta-lipotropin levels

occurred in 6 out of 16 patients, namely those where SCS gave the major pain relief. These data confirm the

derangement of the endogenous opioid system in chronic pain conditions and suggest that the beta-

endorphin response to SCS could have clinical value in predicting the success of treatment

SO - Applied Neurophysiology 1988;51:324-332

UI - 000088

AU - Yaster M

AU - Deshpande JK

TI - Management of pediatric pain with opioid analgesics. [Review]

AB - We have attempted to dispel many of the myths and misconceptions surrounding the use of narcotic

analgesics in the treatment of childhood pain. Our hope is that an improved understanding and the

application of effective, safe therapy will minimize the suffering of the child with acute or chronic pain.

[References: 83]

SO - Journal of Pediatrics 1988;113:421-429

UI - 000175

AU - Zenz M

TI - Epidural opiates and nerve blocks. [Review]

SO - Recent Results in Cancer Research 1988;108:18-27

UI - 000040

AU - Beliaev DG

AU - Frid IA

AU - Genin IB

TI - Analgesic therapy of cancer outpatients. [Russian]

AB - The results of treatment of 164 out-patients with far advanced malignancies for chronic pain syndrome

are discussed. It was found that subarachnoid, peridural and sacral blocks with alcohol, phenol glycerine and

carbolic acid can relieve pain for a long time, improve general condition and save narcotic analgetics. The

most effective proved to be peridural block by phenolglycerine which induced analgesia in 67% of cases and

maintained it for 45 days

SO - Voprosy Onkologii 1987;33:85-90

UI - 000106

AU - Boersma FP

AU - Buist AB

AU - Thie J

TI - Epidural pain treatment in the northern Netherlands. Organizational and treatment aspects

AB - During the past six years opiates administered in the vicinity of the medulla spinalis (intrathecally or

extradurally) were shown to be successful tools in the treatment of both acute and chronic pain (1, 6).

Continuous installation and long-term treatment have become possible by insertion of a permanent catheter

into the epidural space. In cases where conventional analgesic therapy has remained ineffective or given rise

to serious side-effects this method of analgesia should be preferred to control protracted painful conditions,

most typically in cancer patients. This article presents the results of a number of cases of long-term treatment

with extradural opiates and mainly focuses on outpatient treatment and the organization this requires

SO - Acta Anaesthesiologica Belgica 1987;38:213-216

UI - 000103

AU - Bonica JJ

TI - Importance of effective pain control. [Review]

AB - Although the scientific study of pain in the modern sense was initiated 150 years ago, and a number of

theories were subsequently proposed, until two decades ago pain research remained conceptually stagnant

and the meager amount done was not commensurate with the magnitude and clinical importance of pain.

Consequently, pain treatment remained somewhat empirical and ineffective. Moreover, the knowledge and

effective therapeutic modalities that were available were not properly applied, primarily because medical

students and physicians were not taught the basic principles of pain management. Fortunately, during the

past 20 years significant advances have been made in our knowledge of basic mechanisms of acute pain and

about some chronic pain syndromes, and a variety of new therapeutic modalities have been introduced and

old ones have been refined. Among the most important advances of the past decade have been the discovery

of opiate receptors, the extensive pharmacokinetic and pharmacodynamic studies of narcotics, the

development of very sensitive analytic techniques and mathematic knowledge and many other advances

which have prompted the development of new drugs, novel drug preparations and novel methods of

administration, of which intraspinal narcotic therapy is the most important and widely used. [References:


SO - Acta Anaesthesiologica Scandinavica, Supplement 1987;85:1-16

UI - 000099

AU - Bovill JG

TI - Which potent opioid? Important criteria for selection

AB - Opioids remain the drugs of choice for the treatment of severe pain. In recent years several new potent

opioids have become available for clinical use. These newer drugs are generally safer than the older

morphine-like compounds and their differing pharmacological and pharmacokinetic properties allow the

physician to choose an appropriate drug according to the clinical situation and need of an individual patient.

These drugs are classified according to their activity at the opioid receptors. The opioid agonists produce

their pharmacological effect by an almost exclusive action at mu-receptors. The agonist-antagonist group are

kappa-receptor agonists and either competitive antagonists at the mu-receptor or weak mu-agonists. The use

of the potent opioid agonists, because of their potential for causing respiratory depression, is restricted to

hospitals. Fentanyl, the oldest drug of this class, is extensively used as a supplement to general anaesthesia,

or in high doses as a 'complete' anaesthetic for patients undergoing cardiac surgery. Alfentanil and sufentanil

are newer fentanyl derivatives. Alfentanil is unique in having a very short elimination half-life. This is a

particular advantage during short operations and for day-case surgery. For longer operations alfentanil can

be given as a continuous infusion to supplement nitrous oxide anaesthesia. Sufentanil is about 10 times more

potent than fentanyl and is more rapidly eliminated. Initial reports suggest that it may be more effective than

fentanyl as an anaesthetic supplement and that recovery may be more rapid. Both sufentanil and alfentanil

are also used in cardiac anaesthesia. The newer agonist-antagonist opioids, butorphanol, nalbuphine and

buprenorphine, have largely replaced pentazocine in clinical practice. Unlike pentazocine, they cause a low

incidence of dysphoric side effects. Like the pure agonists, they cause respiratory depression; however, in

contrast to the pure agonists this is not dose related, reaching a 'ceiling' as dose increases. The risk of

dependence is also less, so that these drugs are safer for the treatment of chronic pain. Additionally, it is

particularly worth noting that buprenorphine and nalbuphine cause minimal cardiovascular changes, and are

safe and effective drugs for treatment of pain associated with myocardial infarction. Buprenorphine, which is

effective parenterally, orally and sublingually, has a prolonged duration of action (up to 12 hours after a

single dose)

SO - Drugs 1987;33:520-530

UI - 000037

AU - Bruera E

AU - Brenneis C

AU - Michaud M

AU - Chadwick S

AU - MacDonald RN

TI - Continuous sc infusion of narcotics using a portable disposable device in patients with advanced


AB - Fifty-six patients with chronic pain due to advanced cancer were treated with an sc infusion of

morphone (34 patients) or hydromorphone (22 patients) using a portable disposable infusor. The infusion

was maintained for 26 +/- 14 days. Twenty-five patients (45%) were discharged to the home for a mean

period of 18 days (range, 2-138). The mean daily increase in dose was 2.6% +/- 1.4% of the initial dose. The

sc site needed to be changed every 8 days (range, 2-31). Local toxicity consisted of infection in two patients

(3%), chemical irritation in three (5%), and bleeding in one (2%). After 48 hours of treatment, 54 of 56

patients (96%) preferred the sc infusion to their previous parenteral treatment. We conclude that this is a

safe and simple method for the administration of narcotics to inpatients and outpatients

SO - Cancer Treatment Reports 1987;71:635-637

UI - 000042

AU - Bruera E

AU - Chadwick S

AU - Brenneis C

AU - Hanson J

AU - MacDonald RN

TI - Methylphenidate associated with narcotics for the treatment of cancer pain

AB - Thirty-two patients with chronic pain due to advanced cancer were treated with methylphenidate (10

mg with breakfast and 5 mg with lunch) for 3 days, versus placebo, in a randomized, double-blind, cross-

over study designed to evaluate the capacity of methylphenidate to potentiate the analgesic effect of

narcotics and/or to decrease sedation induced by narcotics. In 28 evaluable patients, the intensity of pain

(visual analogue 0-100) and intake of extra doses of analgesics (number of doses/day) were 43 +/- 27 and

2.2 +/- 2.4 during methylphenidate, versus 55 +/- 24 (P less than 0.02) and 2.9 +/- 2.9 (P less than 0.002)

during placebo, respectively. Activity and drowsiness (visual analogue 0-100) were 57 +/- 25 and 58 +/- 24

after methylphenidate, respectively, versus 41 +/- 26 (P less than 0.05) and 45 +/- 27 (P less than 0.02) after

placebo. Upon completion of the study, the investigator and the patient chose methylphenidate blindly as a

more useful drug in 23 cases (83%) and 20 cases (70%), respectively (P less than 0.02). No cases of severe

toxicity were observed. We conclude that methylphenidate can increase the analgesic effect and decrease

sedation of narcotics in this population

SO - Cancer Treatment Reports 1987;71:67-70

UI - 000039

AU - Carmody J

AU - Cooper K

TI - Swim stress reduces chronic pain in mice through an opioid mechanism

AB - Chronic nociception has been studied in male mice by means of the formalin test in which forelimb

motor behaviour is scored after subcutaneous formalin injection. The rating remained above 2.0 for 30 min

after the injection (scale range 0-3). The magnitude of the nociception has been compared with that reported

in other animal types. Mice are more sensitive than rats, cats and monkeys. The stress of a swim of 3 min has

been found to reduce nociception by up to 25%. This analgesia is wholly opioid in nature, being abolished by

a moderate dose of naloxone (1 mg/kg)

SO - Neuroscience Letters 1987;74:358-363

UI - 000033

AU - Colpaert FC

AU - Bervoets KJ

AU - Van den Hoogen RH

TI - Pharmacological analysis of hyperventilation in arthritic rats

AB - The study examined the validity of increased minute volume of ventilation as a measurement of

chronic pain in arthritic rats. The opiates morphine and R 62 818 attenuated arthritic hyperventilation, but

only at doses which also reduced the ventilatory response to CO2 in normal rats. The non-steroidal anti-

inflammatory drugs (NSAIDs), indomethacin and suprofen, the corticosteroids, cortisone and

dexamethasone, and the tranquillizers, haloperidol and chlordiazepoxide, were essentially ineffective except

at doses that also produced anti-inflammatory and/or toxic effects. A combination of an in itself ineffective

dose of R 62 818 with an ineffective dose of suprofen did attenuate arthritic hyperventilation, and the

combination constituted the only pharmacological treatment that did so in the absence of anti-inflammatory,

toxic or intrinsic respiratory effects. The data are consistent with the hypothesis that pain rather than acidosis

mediates arthritic hyperventilation. They also suggest that combinations of an opiate with an NSAID may

perhaps be effective in alleviating this pain

SO - Pain 1987;30:243-258

UI - 000108

AU - Dickenson AH

AU - Sullivan AF

TI - Subcutaneous formalin-induced activity of dorsal horn neurones in the rat: differential response

to an intrathecal opiate administered pre or post formalin

AB - Many studies of pain and nociception use short-lasting acute stimuli which may have limited relevance

to prolonged or chronic pain states. Using extracellular single-unit recording in the dorsal horn of the rat

lumbar spinal cord the present study examines the response of neurones to a long-lasting nociceptive

stimulus, i.e., 50 microliter 5% formalin injected into the corresponding receptive field in the ipsilateral hind

paw, and modulation of this response by an opioid. Formalin produced a distinct biphasic excitatory

response in all convergent neurones tested; an immediate acute or phasic peak of neuronal firing (mean

maximum 22 spikes/sec) 0-10 min post injection, and a second more prolonged tonic excitatory response

(mean maximum 12 spikes/sec) over a period 20-65 min after formalin. Cells only activated by innocuous

stimuli were not excited by formalin indicating the involvement of C fibre afferents in the excitatory response

of convergent neurones to formalin. Both the biphasic nature and the time course of the neuronal response

are similar to those observed in behavioural studies. Intrathecal DAGO (Tyr-D-AlaGlyMePheGly-ol), a

potent and selective mu opioid receptor agonist, applied 20 min prior to formalin completely inhibited both

peaks of excitation. Co-administration of intrathecal naloxone with the agonist restored the biphasic

response. By contrast, when the administration of naloxone was delayed to 2 min post formalin so that

inhibition of the first peak by DAGO pretreatment occurred, there was no subsequent second peak of

activity although antagonism of the opioid would have occurred. When DAGO was applied 2 min post

formalin so the initial acute response occurred, the inhibitory effect of the agonist on the second peak was

far less. Thus the relative ability of DAGO to modulate the biphasic excitatory response of cells to formalin

depends on whether the agonist is administered prior to or after the formalin and the appearance of the

second peak may depend on the presence of the first. These results are discussed in light of the role of these

neurones in nociception, opioid effects and changes in neural systems following peripheral stimuli

SO - Pain 1987;30:349-360

UI - 000102

AU - Hanks GW

TI - The clinical usefulness of agonist-antagonistic opioid analgesics in chronic pain. [Review]

AB - The mixed agonist-antagonist analgesics do not have a major role in the treatment of chronic pain.

Pentazocine, the first and most widely used of this group of drugs has two major limitations: by mouth it is

not a strong analgesic, but is closer in efficacy to the peripherally acting drugs aspirin and paracetamol than

the weak opioids; and its use is associated with psychotomimetic side effects in 10-20 percent of patients.

The weak opioid analgesics codeine and dextropropoxyphene are more effective and better tolerated than

pentazocine. Buprenorphine is the most useful of the agonist-antagonists in chronic pain patients. It is

potent, long-acting (6-9 h) and effective when given sublingually. However, it has a limited effective dose

range and produces the same side effects as morphine-like drugs, possibly more frequently at equianalgesic

doses. It may be used in the treatment of cancer pain, or in patients with chronic arthritides or other forms of

chronic non-cancer pain who require a potent conventional analgesic, as an alternative to the weak opioids

or to morphine in low doses. Nalbuphine and butorphanol are only available for parenteral administration

which means that their usefulness in the treatment of chronic pain is limited. Meptazinol is restricted by its

manufacturers to 'short term' treatment and there is little information on its use in chronic pain patients.

[References: 46]

SO - Drug & Alcohol Dependence 1987;20:339-346

UI - 000028

AU - Hanks GW

TI - The clinical usefulness of agonist-antagonistic opioid analgesics in chronic pain

AB - IN: U London, Inst of Cancer Research, England LA: English AB: Contends that the mixed agonist-

antagonist analgesics do not have a major role in the treatment of chronic pain. Pentazocine, the first and

most widely used of this group of drugs has 2 major limitations: by mouth it is not a strong analgesic, and its

use is associated with psychotomimetic side effects in 10-20% of patients. The weak opioid analgesics

codeine and dextropropoxyphene are more effective and better tolerated. Buprenorphine is the most useful

of the agonist-antagonists in chronic pain patients. However, it has a limited effective dose range and

produces the same side effects as morphine-like drugs. Nalbuphine and butorphanol are only available for

parenteral administration, which means that their usefulness in the treatment of chronic pain is limited.

Meptazinol is restricted by its manufacturers to short term treatment and there is little information on its use

in chronic pain patients. (PsycLIT Database Copyright 1989 American Psychological Assn, all rights

reserved) KP: utility of pentazocine vs butorphanol vs nalbuphine vs buprenorphine vs meptazinol in

treatment of chronic pain AN: 76-02480

SO - Drug and Alcohol Dependence 1987;20:339-346

UI - 000100

AU - Herrmann WM

AU - Kern U

AU - Aigner M

TI - On the adverse reactions and efficacy of long-term treatment with flupirtine: preliminary results

of an ongoing twelve-month study with 200 patients suffering from chronic pain states in arthrosis or


AB - In order to investigate the efficacy and safety of long-term treatment with flupirtine in patients with

chronic pain, in particular arthrosis and arthritis, a study was planned which, when completed, will

encompass the treatment of 200 patients over a 12-month period. The present paper is a preliminary report

of this ongoing study. The report deals with 104 patients: 55 of whom completed the 12-month treatment

period and a 2-week follow-up phase, during which flupirtine was replaced by placebo in order to be able to

detect drug-withdrawal effects. Forty nine patients withdrew from the study. Most of the patients were

suffering from degenerative rheumatic arthrosis or inflammatory rheumatic arthritis. The average daily

dosage was 300 mg. The incidence of drop-outs was highest in the first months with hardly any patients

withdrawing in the last six months. Fifteen patients dropped out because of side effects (dizziness, nausea,

sleep disturbances, and headache). Ten patients dropped out because of ineffectiveness, seven because of

side effects plus ineffectiveness, and three because of side effects and other reasons. The remaining 14

patients dropped out because of other or non-medical reasons. For the 55 patients who completed the study,

the analgesic took effect within 45 minutes to 2 hours, the duration of effect was 4-6 hours. Three-quarters

of the patients responded to the drug, one-quarter did not. The analgesic effect remained constant during the

12-month treatment, as did the average number of capsules taken per month. There was no evidence that

tolerance developed. The most frequent side effects were drowsiness (9% of patients), dizziness (11%), dry

mouth (5%) and pruritis (9%). The withdrawal symptom scale completed every month during treatment (to

determine baseline values) and every day throughout the 2-week placebo post-treatment phase showed no

changes in the median. The mean value increased during the withdrawal phase, however, indicating that the

symptomatology was more pronounced in some subjects. After withdrawal, the non-specific symptoms

increased to a greater extent than symptoms from the opiate scale. The symptoms were present throughout

the withdrawal phase. If the withdrawal phenomena had corresponded to the flupirtine's terminal half-life,

then the symptoms ought to have been present mainly in the first few days. There was a slight trend for

lowering systolic blood pressure but no changes in diastolic blood pressure or heart rate, nor changes in the

ECG or laboratory analysis that could be related to flupirtine.(ABSTRACT TRUNCATED AT 400


SO - Postgraduate Medical Journal 1987;63 Suppl 3:87-103

UI - 000034

AU - Isakova ME

AU - Larionova VB

AU - Sidorkin VA

AU - Tsirikhov SM

TI - Treatment of the pain syndrome in cancer patients by peridural administration of low doses of

opiates. [Russian]

AB - Peridural injections of morphine were given to 180 incurable cancer patients suffering chronic pain.

The effectiveness of the said procedure as well as its side-effects were assessed. A relationship between the

external respiration parameters, on the one hand, and drug dosage and time postinjection, on the other, was

studied. The data obtained point to the effectiveness of the said method and suggest that it be used as a

universal procedure for the treatment of intractable pain in incurable patients

SO - Voprosy Onkologii 1987;33:94-97

UI - 000096

AU - Jimenez AC

AU - Gusmorino P

AU - Pinter I

AU - Snow B

TI - The use of clonidine for the treatment of meperidine withdrawal in a multidisciplinary pain

program setting. A case presentation

AB - The management of iatrogenic drug dependence in individuals with pain can be more difficult than the

treatment of the pain itself. In addition to a multidisciplinary approach to the treatment of a patient with

chronic pain, there is a need for a rapid, safe, and effective method of detoxification from opiate use.

Clonidine HCl, a nonopiate, has been found, in this case presentation, to be a valuable option

SO - Bulletin of the Hospital for Joint Diseases Orthopaedic Institute 1987;47:72-77

UI - 000098

AU - Kriegler JS

AU - Ashenberg ZS

TI - Management of chronic low back pain: a comprehensive approach. [Review]

AB - The treatment approach presented in this article is an obvious departure from ways physicians are

typically trained to handle patients' pain complaints. Traditional medical training focuses primarily on the

management of acute pain. Unfortunately, the treatment modalities appropriate for acute pain are not

applicable to most chronic pain disorders. Since physicians' practices contain many chronic pain patients, it is

important for them to develop a more comprehensive and effective approach to the management of CLBP.

Through the use of case vignettes, this article has attempted to elucidate some common problems

experienced by patients with CLBP. It is a complex disorder that requires that the physicians be sensitive to

the biologic, psychologic, and social aspects of the illness. Simply handing a patient with CLBP a set of back

exercises or prescriptions for narcotics and sedatives will not be beneficial. Rather, the patient must be

educated about the pain and taught to take an active role in his own treatment. By working with patients and

their families, physicians can teach patients with CLBP the self-management skills essential for the

resumption of a normal, productive life. [References: 30]

SO - Seminars in Neurology 1987;7:303-312

UI - 000035

AU - Meyers FJ

AU - Meyers FH

TI - Management of chronic pain

AB - Relief of pain without drug toxicity can be achieved in cancer patients by adhering to basic

pharmacologic principles. Agents should be chosen on the basis of potency and route of administration.

Tolerance can be dealt with by combining different classes of drugs, such as phenothiazines and aspirin, and

by using special routes of administration. Patients with severe pain from illnesses other than cancer can be

effectively palliated in a similar manner

SO - American Family Physician 1987;36:139-146

UI - 000095

AU - Millan MJ

AU - Morris BJ

AU - Colpaert FC

AU - Herz A

TI - A model of chronic pain in the rat: high-resolution neuroanatomical approach identifies

alterations in multiple opioid systems in the periaqueductal grey

AB - Inoculation of the tail base of rats with Mycobacterium butyricum led to an arthritic swelling and

inflammation of the limbs which displayed a hyperalgesia to noxious pressure: these effects peaked at 3

weeks postinoculation. In vitro autoradiography of coronal sections of rat brain was used for a parallel

determination of binding to mu-, delta- and kappa-opioid binding sites. In only two regions, the dorsomedial

and dorsolateral parts of the periaqueductal grey (PAG), was a significant change seen: this comprised an

increase in binding to kappa-sites, whereas mu- and delta-sites therein were unaffected. This region was

analysed for opioid peptides derived from each of the three opioid peptide families known. While no change

was seen in levels of immunoreactive (ir)-dynorphin1-17 A (DYN) and ir-Met-enkephalin, a decrease was

detected in those of ir-beta-endorphin (beta-EP): this change was restricted to the PAG. These data

demonstrate a highly localized and selective influence of chronic arthritic pain upon multiple opioid systems

in the PAG of the rat, a structure playing a key role in the control of pain and in the expression of the

antinociceptive actions of opioids. The data suggest a possible significance of PAG pools of beta-EP and

kappa-receptors in the response to and modulation of chronic pain

SO - Brain Research 1987;416:349-353

UI - 000097

AU - Millan MJ

AU - Czlonkowski A

AU - Pilcher CW

AU - Almeida OF

AU - Millan MH

AU - Colpaert FC

AU - Herz A

TI - A model of chronic pain in the rat: functional correlates of alterations in the activity of opioid


AB - Intradermal inoculation of rats at the tail base with Mycobacterium butyricum led to the gradual

development of an arthritic swelling of the limbs which peaked at 3 weeks and subsided thereafter. Arthritic

rats displayed a loss of body weight, hypophagia, and hypodipsia in addition to a disruption of the diurnal

rhythms of ingestive behavior and of core temperature. The activity of adenohypophyseal beta-endorphin-

(beta-EP) secreting corticotrophs, in contrast to prolactin-(PRL) secreting lactotrophs, was increased in

arthritic rats. Indeed, hypertrophy of the adrenal glands was seen. Arthritic rats also showed an elevation in

spinal cord levels of immunoreactive dynorphin (DYN), an endogenous ligand of the kappa-opioid receptor.

The paws and tail of arthritic rats showed lower thresholds in response to noxious pressure (hyperalgesia),

higher thresholds in response to noxious heat (hypoalgesia), and no change in their response to noxious

electrical stimulation. Neither naloxone nor ICI-154, 129 (a preferential delta-receptor antagonist) modified

the responses of the paw or tail to pressure. However, MR 2266 (an antagonist with higher activity at

kappa-receptors) decreased thresholds to pressure in arthritic, but not control, rats; that is, it potentiated the

hyperalgesia. This action was stereospecific. None of the antagonists modified the response to heat. MR

2266 did not affect the response to pressure in rats with acute inflammation produced by yeast. Thus, the

potentiation of pressure hyperalgesia by MR 2266 in chronic arthritic rats is highly selective. Arthritic rats

showed a reduced response to the analgesic effect of a kappa-agonist (U-50, 488H), whereas the response

to a mu-agonist (morphine) was enhanced. These effects were specific to nociception in that their influence

upon endocrine secretion (PRL and beta-EP) was otherwise changed. The secretion of beta-EP and PRL

was stimulated by both morphine and U-50,488H, and the influence of U-50,488H upon the release of beta-

EP (from the adenohypophysis) was enhanced in arthritic rats. It is suggested that polyarthritis is a complex

condition entailing many changes, both behavioral and endocrinological. Further, arthritic rats cannot simply

be described as "hyperalgesic": of critical importance is the nature of the nociceptive stimulus applied. The

parallel alterations in spinal cord pools of DYN and kappa-receptors (see also Millan et al., 1986) and the

changes in the influence on nociception of kappa-agonists and kappa-antagonists suggest an increased

activity of spinal DYN. Thus, spinal kappa-receptors may play a role in the modulation of nociception under


SO - Journal of Neuroscience 1987;7:77-87

UI - 000107

AU - Miller BE

AU - Lipman JJ

AU - Byrne WL

TI - Partial characterization of a novel endogenous opioid in human cerebrospinal fluid

AB - Human cerebrospinal fluid (CSF) contains many uncharacterized endogenous opioids, in addition to

the known enkephalins, endorphins, and dynorphins. These opioids may be separated by gel filtration

chromatography and identified by radioreceptor assay for opioid activity. One region of the chromatographic

elution profile, designated "Peak B" has previously been shown to be related to the pain status of chronic

pain patients. We now report that human Peak B isolated from the CSF of pain-free elective surgery patients

is present at a typical concentration equivalent in activity to 1.4 pmol of morphine sulfate per ml of CSF

measured by radioreceptor assay. At a dose of 0.06 and 0.12 pmol morphine sulfate equivalents of CSF

(MSE), injected into the cerebroventricular system of the mouse, Peak B produced an antinociceptive effect,

the intensity and duration of which was dose-dependent and which was antagonized by naloxone. The mouse

vas deferens (MVD) preparation was inhibited by Peak B in a manner that was sensitive to antagonism by

naloxone only at low (less than 1.0 microM) but not at higher (greater than 6.0 microM) concentrations of

the antagonist. Peak B activity in the MVD assay was unaffected by treatment with trypsin or alpha-


SO - Life Sciences 1987;41:2535-2545

UI - 000036

AU - Miser AW

AU - Dothage JA

AU - Wesley RA

AU - Miser JS

TI - The prevalence of pain in a pediatric and young adult cancer population

AB - The prevalence and nature of pain in the population of children and young adults with malignancy

treated by the Pediatric Branch of the National Cancer Institute were assessed over a 6 month period. One

hundred and thirty-nine patients were evaluated during 161 in-patient days and 195 out-patient clinic visits.

Approximately 50% of the patients assessed in the hospital and 25% of the patients assessed in the out-

patient clinic were found to be experiencing some degree of pain at the time of assessment. Therapy-related

pain predominated in both in-patients and out-patients; only one-third of the pain experienced by in-patients

and less than 20% of the pain experienced by out-patients was due to tumor. Tumor pain was due primarily

to bony invasion. In order to control pain in those individuals experiencing pain, narcotic analgesics were

being used by one-half of the in-patients and one-third of the out-patients. Overall pain control was good,

with the medium visual analogue scale score being 26 mm on a 0-100 mm scale. During the study period 7

patients were identified to have chronic pain for greater than 1 year following eradication of all known tumor

from the site of pain. One was receiving massive doses of narcotics (120 mg/day of methadone) apparently

out of proportion to his underlying pain

SO - Pain 1987;29:73-83

UI - 000041

AU - Obbens EA

AU - Hill CS

AU - Leavens ME

AU - Ruthenbeck SS

AU - Otis F

TI - Intraventricular morphine administration for control of chronic cancer pain

AB - Twenty cancer patients with severe chronic pain have been treated with intraventricular morphine

sulfate. Adequate pain relief until death was achieved in 10 patients; 1 patient has been treated for 9 months

and is still being treated. In 2 patients, the effects of the morphine sulfate on their unilateral pelvic pain wore

off after 4 and 6 months because of tumor progression. At that time, they underwent chordotomy

procedures elsewhere. The treatment was discontinued in 4 patients for reasons other than inadequate pain

relief, such as medical complications or resolution of pain. In 3 patients, the procedure was abandoned when

emotional and psychological factors interfered with pain control. Dose requirements of intraventricular

morphine sulfate varied greatly, depending on the total daily dose of systemic narcotic intake at the onset of

the study. Intraventricular morphine sulfate is a feasible and reliable method to achieve pain relief in selected

cancer patients with severe chronic pain when the maximum tolerated dose of systemic narcotic analgesics

has become insufficient to control their pain

SO - Pain 1987;28:61-68

UI - 000105

AU - Paladini VA

AU - Gioseffi M

AU - Benvegnu M

AU - Signoretto F

AU - Gobbato E

AU - Mocavero G

TI - Parenteral opiates and late somatosensory evoked potentials in chronic pain. [Italian]

SO - Minerva Anestesiologica 1987;53:535-542

UI - 000195

AU - Portenoy RK

TI - Continuous intravenous infusion of opioid drugs

AB - AB - Continuous intravenous infusion of opioid drugs is a widely accepted alternative approach to the

management of cancer pain. This review critically evaluates the safety and efficacy of the technique and

proffers guidelines for management based on the available literature and clinical experience AD - Albert

Einstein College of Medicine AD - Bronx AD - New York UI - 87143234

SO - Med Clin North Am 1987;71:233-241

UI - 000197

AU - Portenoy RK


AB - AB - General considerations in the administration of opioids to cancer patients are discussed, and the

available routes of administration are described, including how they are used and with which drugs. The

routes of administration covered are oral, buccal, sublingual, rectal, parenteral (continuous iv administration,

continuous sc administration, and patient-controlled analgesia), spinal (epidural and intrathecal), and

intraventricular. These routes of administration offer to the clinician many options in the pursuit of a safe,

affordable, and effective method of opioid analgesia for the patient with chronic cancer pain. Regular dosing

with oral medication offers the simplest, most reliable, and least expensive method of pain control; it remains

the preferred approach. There should be a specific indication for the use of any particular route of

administration. Appropriate use of these administration routes depends on careful assessment of the patient

and detailed knowledge of both the literature and the clinical utility relevant to each. (22 Refs) AD - Dept. of

Neurology AD - Albert Einstein Coll. of Medicine AD - Bronx AD - NY UI - 88645128

SO - Cancer Nurs 1987;10:138-142

UI - 000193

AU - Portenoy RK

TI - Optimal pain control in elderly cancer patients

AB - The optimal management of pain in the elderly cancer patient is founded on astute assessment of pain

and other symptoms, development of a pain diagnosis derived from the clinical evaluation, treatment of

underlying causes where possible, and the expert application of analgesic techniques. Analgesic techniques

themselves are multimodal. Pharmacologic approaches are the mainstay, but an individual patient may

benefit from the use of anesthetic, neuroaugmentative, surgical, physiatric, or psychological methods, as

well. Guidelines for the assessment and integrated management of these patients are suggested, with specific

emphasis on the use of pharmacologic therapy AD - Unified Pain Service AD - Albert Einstein College of

Medicine AD - Bronx AD - New York UI - 87192031

SO - Geriatrics 1987;42:33-6, 39-40, 44

UI - 000101

AU - Przewlocki R

TI - Opioid peptides in relation to antinociception. [Review]

AB - Three families of endogenous opioid peptides, each derived from distinct precursor, as well as their

localization, affinity and interaction with different subtypes of opioid receptors are described. The release of

opioid peptides upon various stimulation procedures is also presented. The emphasis is made on the role of

opioid peptides in analgesia by describing their antinociceptive potency and discussing the role of peptides

deriving from the different precursors in conveying the acute pain stimuli and on the changes in activity of

opioid peptide systems in chronic pain. [References: 88]

SO - Polish Journal of Pharmacology & Pharmacy 1987;39:609-621

UI - 000038

AU - Scherrer P

AU - Schelling JL

TI - Drug therapy of chronic pain in cancer patients. Survey among hospitalized patients. [French]

SO - Revue Medicale de la Suisse Romande 1987;107:69-76

UI - 000104

AU - Young RF

AU - Chambi VI

TI - Pain relief by electrical stimulation of the periaqueductal and periventricular gray matter.

Evidence for a non-opioid mechanism

AB - Pain relief following stimulation of the periaqueductal gray matter (PAG) or periventricular gray

matter (PVG) in man has been ascribed to stimulation-induced release of endogenous opioid substances.

Forty-five patients were studied and followed for at least 1 year after placement of chronic stimulating

electrodes in the PAG or PVG to determine if pain relief due to stimulation could be ascribed to an

endogenous opioid mechanism. Three criteria were assessed: the development of tolerance to stimulation;

the possibility of cross-tolerance to morphine; and reversibility of stimulation-induced pain relief by the

opiate antagonist naloxone. Sixteen patients (35.6%) developed tolerance to stimulation, that is, they

obtained progressively less effective pain relief. Twelve (44.4%) of 27 patients undergoing stimulation of the

thalamic sensory relay nuclei for treatment of chronic pain (a presumably non-opioid mechanism) also

developed tolerance. Morphine sulfate was administered in a blind, placebo-controlled protocol to 10

patients who had become tolerant to PAG-PVG stimulation and none showed evidence of cross-tolerance.

Fifteen of 19 patients, already tolerant to morphine at the time of PAG-PVG electrode implantation,

experienced excellent pain relief by stimulation, also indicating a lack of cross-tolerance. Twenty-two

patients who experienced excellent pain relief from chronic PAG-PVG stimulation received intravenous

naloxone in a double-blind, placebo-controlled protocol. Pain intensity as assessed by the visual analog scale

was increased to the same degree by both placebo and naloxone. Eight patients showed no increase in pain

intensity with either placebo or naloxone. Although tolerance to PAG-PVG stimulation developed in these

patients, the frequency of tolerance was similar to that seen in patients undergoing thalamic sensory nuclear

stimulation. Since the latter technique presumably relieves pain by a non-opioid mechanism, the development

of tolerance to PAG-PVG stimulation does not, in itself, confirm an opioid mechanism. Cross-tolerance

between PAG-PVG stimulation and morphine was not seen and cross-tolerance to PAG-PVG stimulation in

patients already tolerant to morphine was rare. The pain-relieving effect of PAG-PVG stimulation was

reversed to an approximately equal degree by naloxone and placebo. The authors do not believe that, in

most patients, pain relief elicited by PAG-PVG stimulation depends on an endogenous opioid mechanism. It

appears that other, non-opioid mechanisms are primarily responsible for such pain relief

SO - Journal of Neurosurgery 1987;66:364-371

UI - 000176

AU - Zenz M

TI - Therapy of pain caused by gastrointestinal tumors. [German]

AB - Therapy of pain induced by malignant diseases is an important task for any physician. A proper

diagnosis is necessary for an adequate treatment. Pain in the bones can be treated successfully with

peripherally acting analgesics such as acetylsalicylic acid, paracetamol or metamizole. On the other hand,

certain tumors require local blockade as in cases with pancreatic or perianal tumors. If such a therapeutic

approach is not possible or if pain is felt all over the body then centrally acting analgesics such as opiates are

necessary. Opiates should be administered according to a tight schedule and not on demand. Combinations

of certain analgesic drugs are often quite useful. Apart from their peripheral application opiates can also be

administered epidurally or intrathecally which reduces the required dosage

SO - Leber, Magen, Darm 1987;17:238-243

UI - 000054

AU - Bach V

AU - Carl P

AU - Ravlo O

AU - Crawford ME

AU - Werner M

TI - Potentiation of epidural opioids with epidural droperidol. A one year retrospective study

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AB - During a period of one year, 119 patients with chronic pain received injections of opioids via a

catheter inserted in the lumbar epidural space. Twenty-three patients (19%) showed evidence of tolerance

and were given droperidol 1.25-5.0 mg epidurally. In 20 patients in this study, there was a significant

reduction in the number of epidural opioid injections. Six patients complained of excessive sedation, which

disappeared when the dose of droperidol was reduced, although this did not affect the analgesia. One patient

given an accidental overdose of droperidol developed reversible Parkinsonism. It is concluded that epidural

administration of the dopamine antagonist droperidol may be beneficial as supplementary medication to

epidural opioids when tolerance develops

SO - Anaesthesia 1986;41:1116-1119

UI - 000052

AU - Baskin DS

AU - Mehler WR

AU - Hosobuchi Y

AU - Richardson DE

AU - Adams JE

AU - Flitter MA

TI - Autopsy analysis of the safety, efficacy and cartography of electrical stimulation of the central

gray in humans

AB - Electrical brain stimulation is effective in controlling certain intractable chronic pain syndromes in

humans, but the specific target site(s) for stimulation producing a maximal analgesic effect is (are) not well

defined. This prospective study correlates the clinical results of chronic stimulation of the periaqueductal

gray (PAG) and periventricular gray (PVG) matter in humans with the anatomic site of electrode placement

as determined at autopsy, and documents the histologic reactions to electrode implantation and electrical

stimulation of the area. Seven patients underwent electrode implantation to control their chronic pain; two

had electrodes implanted bilaterally. All patients obtained complete analgesia with stimulation, although 3

subsequently found the stimulation to have diminished efficacy. The opiate antagonist naloxone reversed the

analgesia in the 4 patients so tested. All 7 patients later died of causes unrelated to electrode implantation or

stimulation. Postmortem analysis showed that, for 6 of the 9 electrodes implanted, the electrode tip was

located in the ventrolateral PAG at the level of the posterior commissure; the other 3 electrodes were found

in the white matter adjacent to the PAG. No evidence of gliosis or parenchymal reaction was observed along

the tracts and tips of the electrodes. The results indicate that the ventrolateral PAG and PVG matter at the

level of the posterior commissure is the optimal site for therapeutic electrical brain stimulation for opiate-

responsive pain in humans

SO - Brain Research 1986;371:231-236

UI - 000056

AU - Baumann TJ

AU - Batenhorst RL

AU - Graves DA

AU - Foster TS

AU - Bennett RL

TI - Patient-controlled analgesia in the terminally ill cancer patient

AB - Patient-controlled analgesia (PCA) is a relatively new therapeutic modality which has allowed

postsurgical patients to safely and effectively self-administer doses of intravenous narcotics via a syringe

pump and sequencing device. A pilot study was designed to evaluate PCA's safety and effectiveness in the

terminally ill cancer patient. Eight patients whose chronic pain was not adequately controlled by oral

narcotics were permitted to use PCA for a minimum of 48 hours. Respiratory rates, sedation rankings, and

pain rankings indicated these patients achieved satisfactory analgesia with a minimum of sedation and

experienced no respiratory depression. Three patients were switched to oral regimens using PCA dosing as a

guide. Pain and sedation rankings were similar to those registered while exclusively on PCA. This self-

dosing technique was judged to be safe, effective, and able to accommodate wide fluctuations in analgesic

need when treating pain in the terminally ill cancer patient. The results obtained in these patients support

further trials using PCA to individualize oral analgesic regimens

SO - Drug Intelligence & Clinical Pharmacy 1986;20:297-301

UI - 000216

AU - Cohen SR

AU - Melzack R

TI - Habenular stimulation produces analgesia in the formalin test

AB - AB - Electrical stimulation of the habenula produces a striking reduction of continuous, formalin-

induced pain in the rat. The analgesia occurs at current levels which do not appear aversive and persists for

variable durations, ranging from 1 to 21 min in this experimental situation. The effect is not blocked by

subcutaneous administration of a large dose of naloxone prior to the stimulation, indicating that it is not

dependent on an opiate-sensitive system. Stimulation of the adjacent paraventricular nucleus of the thalamus

was either aversive or had no effect on the pain scores. The anatomical connections of the habenula suggest

that it may mediate the interaction of limbic forebrain structures with midbrain structures known to play a

role in pain and analgesia UI - 87039849

SO - Neurosci Lett 1986;70:165-169

UI - 000050

AU - Coombs DW

TI - Management of chronic pain by epidural and intrathecal opioids: newer drugs and delivery

systems. [Review]

SO - International Anesthesiology Clinics 1986;24:59-74

UI - 000055

AU - Doleys DM

AU - Dolce JJ

AU - Doleys AL

AU - Crocker M

AU - Wolfe SE

TI - Evaluation, narcotics and behavioral treatment influences on pain ratings in chronic pain


AB - Changes in self-reported pain ratings were assessed in 95 chronic pain patients from data collected at

three times: pretreatment evaluation, initial days of treatment and final days of treatment. These data were

collected separately for regular, sporadic and nonusers of narcotic medication. Each patient completed a

four-week interdisciplinary behaviorally based noninvasive treatment program. There was an average

decrease of 7% in self-reported pain ratings between evaluation and the onset of treatment for the three

groups. An additional decrease of 21%, 16% and 10% for the sporadic, nonusers and regular users of

narcotics respectively was noted during treatment. Statistical analysis revealed a significant decrease in pain

ratings across assessment phases but not between groups. Sporadic users of narcotics showed a pattern

more similar to nonusers than to the regular users

SO - Archives of Physical Medicine & Rehabilitation 1986;67:456-458

UI - 000049

AU - Farkash AE

AU - Portenoy RK

TI - The pharmacological management of chronic pain in the paraplegic patient. [Review]

SO - Journal of the American Paraplegia Society 1986;9:41-50

UI - 000200

AU - Farkash AE

AU - Portenoy RK

TI - The pharmacological management of chronic pain in the paraplegic patient

AB - AB - [No Abstract Available] UI - 87059866

SO - J Am Paraplegia Soc 1986;9:41-50

UI - 000225

AU - Halpern LM

AU - Dong WK

TI - D-phenylalanine: a putative enkephalinase inhibitor studied in a primate acute pain model

AB - D-Phenylalanine, along with morphine, acetylsalicylic acid and zomepirac sodium were evaluated for

their antinociceptive actions in monkeys (M. fascicularis) trained to autoregulate nociceptive stimulation

using a discrete-trials, aversive-threshold paradigm. Morphine sulfate produced dose-related increases in

aversive threshold which were reversible after administration of naloxone (12.5 or 25 micrograms/kg i.m.).

D-Phenylalanine (500 mg/kg p.o.) produced a small increase in aversive threshold which was not statistically

significant and not naloxone reversible. Acetylsalicylic acid (200 mg/kg p.o.) but not zomepirac sodium (200

mg/kg p.o.) in combination with D-phenylalanine (500 mg/kg) produced a small statistically significant

increase in aversive threshold. Our results argue against the hypothesis that D-phenylalanine is responsible

for increasing aversive thresholds via opiate receptor mechanisms involving increased activity of enkephalins

at synaptic loci. Previous studies by others in rats and mice showed that D-phenylalanine and acetylsalicylic

acid produced increases in nociceptive thresholds which were naloxone reversible. Our failure to find opiate

receptor mediated analgesia in a primate model with demonstrated opiate receptor selectivity and sensitivity

is discussed in terms of previous basic and clinical research indicating an analgesic role for D-phenylalanine.

Possible species difference in drug action is discussed in terms of inhibition by D-phenylalanine of carboxy-

peptidase-like enkephalin processing enzymes as well as inhibition of carboxypeptidase-like enkephalin

degrading enzymes UI - 86176317

SO - Pain 1986;24:223-237

UI - 000185

AU - Kanner RM

AU - Portenoy RK

TI - Are the people who need analgesics getting them?

AB - [No Abstract Available]

SO - Am J Nurs 1986;86:589-589

UI - 000189

AU - Kanner RM

AU - Portenoy RK

TI - Are the people who need analgesics getting them?

AB - AB - [No Abstract Available] UI - 86212419

SO - Am J Nurs 1986;86:589-589

UI - 000205

AU - Kanner RM

AU - Portenoy RK

TI - Unavailability of narcotic analgesics for ambulatory cancer patients in New York City

AB - AB - [No Abstract Available] UI - 87035134

SO - J Pain Symptom Manage 1986;1:187-189

UI - 000044

AU - Kayser V

AU - Besson JM

AU - Guilbaud G

TI - Analgesia produced by low doses of the opiate antagonist naloxone in arthritic rats is reduced in

morphine-tolerant animals

AB - In a model of experimental chronic pain (adjuvant-induced arthritic rats), low doses of the opiate

antagonist naloxone produced a profound analgesia. Maximum analgesia was seen with 3 micrograms/kg

(i.v.). In contrast, hyperalgesia was obtained with much higher doses (1-3 mg/kg, i.v.). The hyperalgesic

effects were not affected in arthritic animals rendered tolerant to morphine, but the paradoxical analgesic

effects were significantly reduced. This decrease suggests that naloxone analgesia involves interaction with

opiate receptors and that the operation of endorphinergic systems differs in normal animals and animals

which experience persistent pain

SO - Brain Research 1986;371:37-41

UI - 000031

AU - Millan MJ

AU - Millan MH

AU - Czlonkowski A

AU - Pilcher CWT

AU - Hollt V

AU - Colpaert FC

AU - Herz A

TI - Functional response of multiple opioid systems to chronic arthritic pain in the rat

ED -

BK - Stress-induced analgesia. Annals of the New York Academy of Sciences, Vol. 467. (Dennis D. Kelly,

Ed.), pp. 182-193. New York Academy of Sciences, New York, NY, US; 449 pp.<<SEE BOOK>>


Max-Planck-Inst fur Psychiatrie LA: English SP: Sponsor; Deutsche Forschungsgemeinschaft, Bonn,

Federal Republic of Germany CR: (from the chapter) there is ...a multiplicity of opioid ligands and opioid

receptors that display a differential distribution and modulation and appear to subserve contrasting functional

roles / in addition, there are many independently localized pools of the respective opioid peptides and opioid

receptors / consequently, the often-formulated question as to the role of opioid systems in pain control may

be a misleading oversimplification / it is necessary to examine these questions within the perspective of the

multiplicity of these opioid systems /// summarizes the findings of our recent work in which such an

approach was adopted for an evaluation of the functional response of particular opioid systems to a model of

chronic pain in the rat--adjuvant-induced arthritis

SO - New York, NY, US ,New York Academy of Sciences 1986;:182-193

UI - 000045

AU - Millan MJ

AU - Millan MH

AU - Czlonkowski A

AU - Hollt V

AU - Pilcher CW

AU - Herz A

AU - Colpaert FC

TI - A model of chronic pain in the rat: response of multiple opioid systems to adjuvant-induced arthritis

AB - Chronic arthritic pain was induced by intradermally inoculating rats at the tail-base with

Mycobacterium butyricum, which results in swelling, inflammation, and hyperalgesia of the joints. These

symptoms peak at 3 weeks after inoculation and disappear by 10 weeks. The following changes were seen at

3 weeks. Immunoreactive dynorphin (ir-Dyn) and ir-alpha-neo-endorphin (alpha-NE) manifested comparable

patterns of change. Their levels were increased in the anterior, but not neurointermediate, pituitary. The

thalamus showed a rise in ir-Dyn and ir-alpha-NE, but no alterations were seen in other brain regions. In

each case, cervical, thoracic, and lumbosacral sections of the spinal cord showed a rise in ir-Dyn and ir-

alpha-NE: This was most pronounced in the lumbosacral region, where the magnitude of these shifts

correlated with the intensity of arthritic symptoms. In addition, a moderate elevation in ir-methionine-

enkephalin (ME) was seen in lumbosacral spinal cord. In brain, ir was not changed. The level of ir-beta-

endorphin (beta-EP) was elevated both in the plasma and the anterior, but not the neurointermediate,

pituitary. In addition, the content of messenger RNA encoding the beta-EP precursor, proopiomelanocortin

(POMC), was enhanced in the anterior lobe. Thus, there was a selective activation of synthesis of beta-EP

in, and its secretion from, the anterior lobe. In no brain tissue did levels of ir-beta-EP change. At 10 weeks

postinoculation, the above changes were no longer apparent, indicating their reversibility.(ABSTRACT


SO - Journal of Neuroscience 1986;6:899-906

UI - 000198

AU - Portenoy RK

AU - Moulin DE

AU - Rogers A

AU - Inturrisi CE

AU - Foley KM

TI - I.v. infusion of opioids for cancer pain: clinical review and guidelines for use

AB - AB - To assess the safety, efficacy, and use of continuous iv infusion (CI) of opioids for cancer pain,

we reviewed the clinical experience of 36 patients who received 46 CIs. CI was always preceded by a period

of repetitive dosing of opioids. Morphine was used in 36 CIs, methadone in four, hydromorphone in four,

oxymorphone in one, and levorphanol in one. Mean doses during CI were the morphine equivalent of 17

mg/hour (range, 0.7-100) at the start, 69 mg/hour (range, 4- 480) at the maximum, and 52 mg/hour (range,

1-480) at termination. Pain relief was acceptable during 28 CIs, unacceptable during 17, and unknown

during one. There were few toxic effects other than sedation. Twenty-five patients died, 12 resumed im or

oral opioids, six continued CI with a different opioid (yielding analgesia in two), and outcome was

undetermined in three. This review suggests that (a) CI is safe, (b) analgesia may require rapid escalation of

infusion rates, (c) patient response varies and lack of acceptable analgesia may occur in up to one-third, (d)

ineffective CI with one drug may be followed by success with another, (e) CI should be preceded by a period

of repetitive iv boluses with the same drug, and (f) guidelines can be developed which incorporate

pharmacokinetic principles AD - Department of Neurology AD - Memorial Sloan-Kettering Cancer Center

AD - New York AD - NY 10021 UI - 86217834

SO - Cancer Treat Rep 1986;70:575-581

UI - 000190

AU - Portenoy RK

TI - Continuous infusion of opioids

AB - AB - [No Abstract Available] UI - 86155965

SO - Am J Nurs 1986;86:318, 322-318, 322

UI - 000196

AU - Portenoy RK

AU - Moulin DE

AU - Rogers AG

AU - Inturrisi CE

AU - Foley KM



AB - AB - Continuous iv infusion (CI) of opioid analgesics as an alternative approach to analgesia has

found increasing use in the management of postoperative pain and chronic pain. Despite the popularity of

CI, little documentation exists for its safety and efficacy. In order to assess these concerns, clinical

characteristics of 46 infusions in 36 patients with cancer-related pain were reviewed retrospectively. Hospital

charts were analyzed for patient characteristics, prior opioid exposure, rationale for iv administration of drug

and for CI, course of infusion, and outcome. Details of the characteristics of the study population are

presented in a table. All patients had cancer and all but one had active disease. Thirty-two patients had pain

due to tumor invasion, whereas three had pain caused by cancer therapy and one had pain unrelated to the

diagnosis of cancer. All patients had been exposed to opioid medications before the CI was begun. Thirty-six

infusions were begun with morphine sulfate, while methadone was used in four infusions, hydromorphone in

four, oxymorphone in one, and levorphanol in one. Additional medications, including the opioid analgesics,

were often given during the CI; their nature and frequency of use are tabulated. During 42 infusions, the max

infusion rate was greater than that at the start; during 17 infusions, the rate at CI termination was lower than

the max rate. Three patterns of dosing during CI were observed and are displayed graphically. The duration

of CI ranged from 1 to 45 days. Five patients were treated for less than 3 days, 13 for 4-6 days, 13 for 7- 13

days, 7 for 14-21 days, 3 for 22-29 days, 2 for 30-37 days, and 3 for 38-45 days. For 25 patients, the CI was

maintained until the patients died. Side effects due to the CI were difficult to determine precisely, since

34/46 patients were receiving repetitive iv bolus injections of opioids prior to CI, and the medical conditions

of the patients were often deteriorating during the infusion. Progressive sedation was by far the most

common side effect during CI. Respiratory depression, easily reversed with iv naloxone, occurred in a single

patient who received intrathecal morphine during CI. Safety and efficacy of CI are discussed. Guidelines in

the management of CI are listed in a table. (21 Refs) AD - Pain Research Program AD - Dept. of Neurology

AD - Memorial Sloan-Kettering Cancer Center AD - New York AD - NY 10021 UI - 87637003

SO - Adv Pain Res Ther 1986;8:413-424

UI - 000204

AU - Portenoy RK

TI - Continuous infusion of opioid drugs in the treatment of cancer pain: guidelines for use

AB - AB - [No Abstract Available] UI - 87059287

SO - J Pain Symptom Manage 1986;1:223-228

UI - 000209

AU - Portenoy RK

AU - Foley KM

TI - Chronic use of opioid analgesics in non-malignant pain: report of 38 cases

AB - AB - Thirty-eight patients maintained on opioid analgesics for non- malignant pain were

retrospectively evaluated to determine the indications, course, safety and efficacy of this therapy. Oxycodone

was used by 12 patients, methadone by 7, and levorphanol by 5; others were treated with propoxyphene,

meperidine, codeine, pentazocine, or some combination of these drugs. Nineteen patients were treated for

four or more years at the time of evaluation, while 6 were maintained for more than 7 years. Two-thirds

required less than 20 morphine equivalent mg/day and only 4 took more than 40 mg/day. Patients

occasionally required escalation of dose and/or hospitalization for exacerbation of pain; doses usually

returned to a stable baseline afterward. Twenty-four patients described partial but acceptable or fully

adequate relief of pain, while 14 reported inadequate relief. No patient underwent a surgical procedure for

pain management while receiving therapy. Few substantial gains in employment or social function could be

attributed to the institution of opioid therapy. No toxicity was reported and management became a problem

in only 2 patients, both with a history of prior drug abuse. A critical review of patient characteristics,

including data from the 16 Personality Factor Questionnaire in 24 patients, the Minnesota Multiphasic

Personality Inventory in 23, and detailed psychiatric evaluation in 6, failed to disclose psychological or social

variables capable of explaining the success of long-term management. We conclude that opioid maintenance

therapy can be a safe, salutary and more humane alternative to the options of surgery or no treatment in

those patients with intractable non-malignant pain and no history of drug abuse UI - 86258701

SO - Pain 1986;25:171-186

UI - 000186

AU - Portenoy RK

TI - Continuous infusion of opioids

AB - [No Abstract Available]

SO - Am J Nurs 1986;86:318, 322-318, 322

UI - 000047

AU - Przewlocki R

AU - Lason W

AU - Silberring J

AU - Herz A

AU - Przewlocka B

TI - Release of opioid peptides from the spinal cord of rats subjected to chronic pain

AB - Chronic localized pain increased the level of the opioid peptides, dynorphin (DYN), alpha-

neoendorphin (ANEO), Met-enkephalin (MET) and Mets-enkephalin-Arg6-Gly7-Leu8 (MEAGL), in the

lumbar enlargement of the rat spinal cord. It was accompanied with a reduction of the spontaneous and K+-

stimulated release of ANEO and MEAGL from spinal cord slices in vitro and a decreased release of ANEO

from the spinal cord in vivo. The results indicate that the reduction in the activity of endogenous opioid

peptide systems might occur in the spinal cord of rats subjected to chronic pain

SO - NIDA Research Monograph Series 1986;75:422-425

UI - 000234

AU - Seecof R

AU - Tennant FS Jr.

TI - Subjective perceptions to the intravenous "rush" of heroin and cocaine in opioid addicts

AB - AB - Subjective responses to intravenous heroin and cocaine administration were investigated by

questionnaire in a population of 40 male and 29 female confirmed heroin addicts. Responses of males and

females were very similar for the heroin rush, ranking pleasure, relaxation, satisfaction, warmth, and thirst

highest among 20 feelings surveyed and ranking feelings like sexual orgasm low, only fifteenth out of 20.

Responses of males and females for the cocaine rush were similar in that both ranked excitement, pleasure,

thirst, strength, and anxiety very high, in the top six responses, and both rated feelings like sexual orgasm

relatively low, rank 9 for males and 15 for females. However, male and female responses for cocaine differed

in that males ranked power very high, rank 2; and females ranked power relatively low, rank 10; but ranked

satisfaction, rank 5; warmth, rank 5; and relaxation, rank 12; much higher than males who ranked them 15,

16, and 17, respectively. Despite the fact that sexual feelings were infrequently identified with rushes, the

results best supported an interpretation that the population was largely inorgasmic without drugs, but found

attractive orgasmic pleasure in heroin and cocaine. Males and females perceived the cocaine rush differently,

but the reason of these differences is uncertain UI - 87073331

SO - Am J Drug Alcohol Abuse 1986;12:79-87

UI - 000046

AU - Shatin D

AU - Mullett K

AU - Hults G

TI - Totally implantable spinal cord stimulation for chronic pain: design and efficacy

AB - Neurostimulators used to treat chronic, intractable pain have evolved from technical developments in

pacemaker technology. A totally implantable spinal cord stimulation (SCS) system was designed based on

elements of a widely used cardiac pacemaker. This paper reports on the transformation of pacemaker

technology for neurostimulation applications and presents results of using this system for the treatment of 90

patients with chronic, intractable pain of the low back and/or legs. Significant reduction in pain levels

resulted from use of a totally implantable spinal cord stimulation system. Seventy percent of the patients

experienced good or excellent pain relief at an average of 14.5 months after implant. Patients who used an

automatic ON/OFF cycling mode of stimulation reported greater pain relief than patients who were

stimulated continuously

SO - Pace - Pacing & Clinical Electrophysiology 1986;9:577-583

UI - 000043

AU - Simonnet G

AU - Taquet H

AU - Floras P

AU - Caille JM

AU - Legrand JC

AU - Vincent JD

AU - Cesselin F

TI - Simultaneous determination of radio-immunoassayable methionine-enkephalin and radioreceptor-active

opiate peptides in CSF of chronic pain suffering and non suffering patients

AB - Radio-immunoassayable methionine-enkephalin (ME) and radioreceptor-active opiate peptide levels

(OP) were determined in CSF from patients, both with and without chronic pain, under investigation for

vertebral disk disease. This study showed: that there was no direct correlation between ME and OP levels in

CSF; OP levels were negatively correlated with the ME/OP ratio; migraine patients had higher levels of ME;

ME concentrations were reduced in patients receiving anti-inflammatory drugs (nonsteroidal): patients with

chronic pain (non migraine, no anti-inflammatory drug therapy) had lower ME levels than patients without

pain. The data are discussed in relation to animal models of chronic pain

SO - Neuropeptides 1986;7:229-240

UI - 000051

AU - Staren ED

AU - Cullen ML

TI - Epidural catheter analgesia for the management of postoperative pain. [Review]

AB - Since its introduction to North America in 1942, the use of epidural catheter analgesia has increased

dramatically. Improved equipment, methods and medications have broadened its application to include

among others, surgical anesthesia, chronic pain relief and the management of postoperative pain. Numerous

techniques for epidural puncture and insertion of the catheter have been described. Although complications

have been associated with placement of an epidural catheter, these are rare when performed by an

experienced anesthesiologist. Epidural analgesia was first accomplished by blockade with local anesthetics.

Bupivacaine has been called the local anesthetic of choice for epidural infusion. Bolus administration of

epidural local anesthetics gives effective analgesia; however, its use is limited by brief duration and

occasionally severe hypotension. Epidural local anesthetics have been administered by continuous infusion in

an attempt to minimize side effects. Nevertheless, hypotension, as well as motor block, numbness, nausea

and urinary retention have occurred. Epidural analgesia with local anesthetics is effective in relieving

postoperative pain, but its safety and feasibility have been questioned because of the frequent, potentially

serious side effects. These problems led to trials of epidural narcotics for postoperative pain management.

The exact site of action of epidural narcotic analgesics is debatable; however, the bulk of evidence supports

a direct spinal action. Epidural narcotics appear to specifically inhibit nociceptive stimuli. The prolonged and

profound analgesia that occurs with epidural narcotics relative to parenteral administration is due to a higher

concentration of drug reaching the CSF through the epidural route. Since nervous transmission is not

completely blocked this technique cannot provide anesthesia during operation. Morphine has been the most

frequently used narcotic for epidural analgesia. Results of several recent, randomized double-blind studies

have shown that epidural narcotics give adequate analgesia comparable with that observed with epidural

bupivacaine. Epidural morphine provides a greater duration of analgesia and may cause fewer side effects.

Improved analgesia has been reported when epidural narcotics are used in combination with local

anesthetics. Continuous administration of low dosage epidural narcotics has been shown to have less

frequent side effects than bolus administration. Nevertheless, pruritus, urinary retention, hypotension and

severe respiratory depression have been reported with both methods.(ABSTRACT TRUNCATED AT 400

WORDS) [References: 133]

SO - Surgery, Gynecology & Obstetrics 1986;162:389-404

UI - 000229

AU - Tennant FS Jr.

AU - Rawson RA

AU - Pumphrey E

AU - Seecof R

TI - Clinical experiences with 959 opioid-dependent patients treated with levo-alpha-acetylmethadol


AB - AB - Levo-alpha-acetylmethadol (LAAM) is an orphan drug that will soon be generally available to

treatment facilities. We have recently treated 959 opioid addicts with LAAM for periods up to 36

consecutive months. Three times per week dosing of LAAM proved to be a safe and effective treatment

agent for the majority of subjects. During LAAM induction there is a delay in opioid activity as LAAM

forms its long-acting metabolites, therefore, symptomatic withdrawal medication must usually be

administered during the first 96 hours of treatment to adequately suppress opioid withdrawal symptoms and

prevent self- administration of drugs by the patient. No long-term hepatic toxicity or tumor formation could

be demonstrated by liver function studies and liver-spleen imaging in a subgroup of patients. Some opioid

addicts report that they prefer LAAM over methadone, but the reverse was reported by about 40% of our

patients which suggests that both drugs are needed for adequate maintenance treatment of the opioid-

addicted population AD - UCLA School of Public Health AD - UCLA Center for Health Sciences 90024 UI

- 87112832

SO - J Subst Abuse Treat 1986;3:195-202

UI - 000053

AU - Todd B

TI - Narcotic analgesics for chronic pain. Drugs and the elderly

SO - Geriatric Nursing - New York 1986;7:53-55

UI - 000248

AU - Urban BJ

AU - France RD

AU - Steinberger EK

AU - Scott DL

AU - Maltbie AA

TI - Long-term use of narcotic/antidepressant medication in the management of phantom limb pain

AB - AB - The successful management of 5 consecutive patients with intractable phantom limb pain is

described. The main therapy is a combination of a narcotic and antidepressant. Medication remained

effective during the average observation time of 22 months. There were no signs of habituation or addiction.

We conclude that narcotics can be safely and successfully utilized for long-term management of phantom

limb pain UI - 86176313

SO - Pain 1986;24:191-196

UI - 000048

AU - Wallenstein SL

AU - Kaiko RF

AU - Rogers AG

AU - Houde RW

TI - Crossover trials in clinical analgesic assays: studies of buprenorphine and morphine

AB - Analgesic studies of buprenorphine, a thebaine derivative and potent partial narcotic agonist, were

carried out in patients with cancer who had postoperative or chronic pain. Intramuscular buprenorphine was

compared with intramuscular morphine in a series of sequentially related, twin crossover assays and was

found to be about 25 times as potent as morphine. Side effects were essentially morphine-like. In a second

assay, the acceptability and analgesic activity of sublingual buprenorphine was studied in a 6-dose, balanced,

incomplete block assay, a modification of the twin crossover design employed in the all-intramuscular trial.

Sublingual buprenorphine was found to be about 15 times as potent as intramuscular morphine and was well

accepted by our patients. The 4-dose twin crossover trial in which doses are adjusted sequentially is more

flexible in that a wide range of doses may be studied, but it lacks the ability of the 6-dose design to provide

estimates of the curvature of the dose-response slopes of the study drugs. When first-dose-only data were

analyzed as parallel group assays, the main difference in results compared with the crossover studies was a

decrease in efficiency and sensitivity

SO - Pharmacotherapy 1986;6:228-235

UI - 000062

AU - Auld AW

AU - Maki-Jokela A

AU - Murdoch DM

TI - Intraspinal narcotic analgesia in the treatment of chronic pain

AB - The results of intraspinal narcotic analgesia (INA) in 43 patients with chronic nonmalignant pain

syndromes are reviewed. A protocol has been established to improve proper patient selection and includes

three phases of study. Most of the patients have had INA for 2 years now. In those patients qualifying for

continuous delivery systems (CDS), 65% had good to excellent relief of pain while 34% were considered

failures for a variety of reasons. Apparent tolerance development in many of the patients was, in fact, due to

technical problems with the epidural catheter instead

SO - Spine 1985;10:777-781

UI - 000058

AU - Cherry DA

AU - Gourlay GK

AU - McLachlan M

AU - Cousins MJ

TI - Diagnostic epidural opioid blockade and chronic pain: preliminary report

AB - A technique is described which helps in the differentiation between pain of a mainly physical (organic)

and emotional (psychogenic) basis. This is based upon the patients' subjective response to the epidural

administration of fentanyl and placebo agents. Patients initially had both physical and psychological

assessment in a multidisciplinary pain management unit and because of doubt of the underlying diagnosis,

were subjected to this procedure. Eight patients are described in whom the following solutions were

administered at 20 min intervals: 2 aliquots of normal saline (5 ml) via an epidural catheter; 1 microgram/kg

fentanyl via the epidural catheter; intravenous naloxone 0.4 mg, then, depending upon results obtained, 15-

20 ml 2% plain lignocaine via the epidural catheter. If a patient's visual analogue score decreased following

epidural fentanyl and subsequently increased following naloxone, then a predominantly physical basis for the

pain was likely. In contrast, little change in visual analogue score following fentanyl and naloxone suggested

a diagnosis of a predominantly emotional basis for the pain. The diagnoses were substantiated by subsequent

follow-up and treatment. It is suggested that this test has both prognostic and diagnostic value when used in

the context of thorough physical and psychologic assessment of a patient with chronic pain

SO - Pain 1985;21:143-152

UI - 000215

AU - Cohen SR

AU - Melzack R

TI - Morphine injected into the habenula and dorsal posteromedial thalamus produces analgesia in the

formalin test

AB - AB - Microinjection of morphine into the area of the habenula and dorsal posteromedial thalamus (H-

PMT) produces analgesia for tonic pain as measured by the formalin test in the rat. Control injections of

morphine into sites near the H-PMT result in less or no reduction in pain, indicating that the analgesia

observed is probably due to a site of action within the H-PMT rather than at surrounding neural structures.

The analgesia is fully developed by the first time of testing, 10-16 min following the microinjection, and is

completely reversible by naloxone, an opiate antagonist. The analgesia recorded is most likely due to

morphine's action on the habenula, parafascicular or paraventricular nucleus of the thalamus, or a

combination of these structures UI - 86078584

SO - Brain Res 1985;359:131-139

UI - 000029

AU - Cruzado JA

TI - Peptidos opiaceos, analgesia inducida por estres y sistemas endogenos de control del dolor. (Opioid

peptides, stress-induced analgesia, and endogenous pain-inhibiting systems.)

AB - IN: U Complutense de Madrid, Spain LA: Spanish AB: Reviews the physiological and behavioral

roles of opioid peptides. Emphasis is on their chemical structure, classification, anatomical distribution, and

role in pain modulation, with descriptions given of the basic neural locations involved in pain control.

Involvement of a dysfunction of the endogenous opiate system in the etiopathogenesis of chronic pain is

proposed. The role of opioid peptides in the neural mechanisms of reinforcement, memory,

psychopathology, and cardiovascular control is summarized. (121 ref) (PsycLIT Database Copyright 1987

American Psychological Assn, all rights reserved) KP: physiological & behavioral characteristics of opioid

peptides; pain modulation AN: 74-03300

SO - Informes de Psicologia 1985;4:39-66

UI - 000065

AU - Drexel H

AU - Lang AH

AU - Spiegel RW

AU - Abbrederis K

TI - Pump-guided continuous subcutaneous opiate infusion for the treatment of the most severe pain.


AB - The continuous subcutaneous infusion of opiate, a new approach to the alleviation of severe chronic

pain, has been carried out using a pump system normally employed for the infusion of insulin. Relapses of

pain can be controlled with bolus doses. This mode of application was compared with conventional therapy

in 11 patients. All patients were free of pain during the continuous infusion, but none showed a satisfactory

response during conventional treatment. The improved response under continuous opiate infusion was

attained with much lower doses and thus with fewer side effects. The procedure is therefore highly effective

and well tolerated

SO - Deutsche Medizinische Wochenschrift 1985;110:1063-1067

UI - 000221

AU - Halpern LM

AU - Robinson J

TI - Prescribing practices for pain in drug dependence: a lesson in ignorance

AB - AB - Chronic pain syndromes arise when usual strategies to treat pain and its underlying pathology

fail, excessive reliance on medication is related to increased dysfunction and, there is suspicion of psychiatric

component to the pain behaviors exhibited. Opiate and sedative medications are generally cited as a

contributing factor in the development of chronic non-malignant pain. The recent proliferation of clinics

specializing in treatment of chronic pain and related disorders is a new and interesting development. These

units consider detoxification from sedatives and opiates mandatory if chronic pain is to be treated and

function restored. A literature review shows an amazing paucity of rigorous research in chronic pain patients

which supports the widely held belief that medications contribute to dysfunction in chronic pain thus patients

require detoxification. The following discussion explores the data upon which are based current strategies

for the use of narcotics in chronic pain UI -86183317

SO - Adv Alcohol Subst Abuse 1985;5:135-162

UI - 000064

AU - Halpern LM

AU - Robinson J

TI - Prescribing practices for pain in drug dependence: a lesson in ignorance

AB - Chronic pain syndromes arise when usual strategies to treat pain and its underlying pathology fail,

excessive reliance on medication is related to increased dysfunction and, there is suspicion of psychiatric

component to the pain behaviors exhibited. Opiate and sedative medications are generally cited as a

contributing factor in the development of chronic non-malignant pain. The recent proliferation of clinics

specializing in treatment of chronic pain and related disorders is a new and interesting development. These

units consider detoxification from sedatives and opiates mandatory if chronic pain is to be treated and

function restored. A literature review shows an amazing paucity of rigorous research in chronic pain patients

which supports the widely held belief that medications contribute to dysfunction in chronic pain thus patients

require detoxification. The following discussion explores the data upon which are based current strategies

for the use of narcotics in chronic pain

SO - Advances in Alcohol & Substance Abuse 1985;5:135-162

UI - 000030

AU - Kroening RJ

AU - Oleson TD

TI - Rapid narcotic detoxification in chronic pain patients treated with auricular electroacupuncture and


AB - IN: U California, Pain Management Ctr, Los Angeles LA: English AB: Studied severe narcotic

withdrawal signs that accompany detoxification, using 14 28-63 yr old chronic pain patients taking high

levels of analgesic medications. A rapid narcotic detoxification procedure using auricular electroacupuncture

was applied to Ss, who were to be withdrawn from their opiate medications. All Ss were first switched to

oral methadone. They were then given bilateral electrical stimulation to needles inserted in the "lung" and

"shen men" acupuncture points on the ear, followed by periodic intravenous injections of low doses of

naloxone (0.8-40 mg/day). 12 Ss were completely withdrawn from narcotic medications within 2-7 days, and

they experienced no to minimal side effects. These results are explained by the relationship of

electroacupuncture to the release of endorphins. (44 ref) (PsycLIT Database Copyright 1987 American

Psychological Assn, all rights reserved) KP: auricular electroacupuncture & naloxone; rapid narcotic

detoxification; 28-63 yr old chronic pain patients withdrawn from opiate analgesic therapy AN: 74-02304

SO - International Journal of the Addictions 1985;20:1347-1360

UI - 000063

AU - Michon F

AU - Des Mesnards VG

AU - Girard M

AU - Fischler M

AU - Vourc'h G

TI - Long-term peridural morphine analgesia in neoplastic and vascular pathology. [French]

AB - Epidural analgesia using morphine has been used on 44 patients with intractable chronic pain, resistant

to analgesics (including opiates). The pain was due to cancer in 24 cases, of vascular origin in 20. An

indwelling tunnelized epidural catheter afforded repeated injections of morphine for a long period (up to 129

days) either in hospital or at home. The quality of analgesia achieved was rated as excellent or good, in 68 p.

100 of cases. Two cases only were total failures. Side effects, relatively common, were usually transient and

minor; no case of respiratory depression or of infection has been recorded

SO - Cahiers d Anesthesiologie 1985;33:39-42

UI - 000060

AU - Moulin DE

AU - Max MB

AU - Kaiko RF

AU - Inturrisi CE

AU - Maggard J

AU - Yaksh TL

AU - Foley KM

TI - The analgesic efficacy of intrathecal D-Ala2-D-Leu5-enkephalin in cancer patients with chronic pain

AB - D-Ala-D-Leu-enkephalin (DADL) is a pentapeptide which, compared to morphine, preferentially

binds to the delta receptor. We compared the analgesic and side effects of intrathecal (i.t.) DADL and i.t.

morphine sulfate (MS) in 10 tolerant cancer patients with chronic pain at or below the T12 level who were

receiving inadequate relief or unacceptable side effects from systemic opiates. These patients were given i.t.

DADL and i.t. MS in a randomized, double-blind, cross-over study on separate days at least 1 day apart. I.t.

DADL produced analgesia in all patients tested. Total pain relief was greater with DADL than MS in 6

patients, equal in 1 patient and less with DADL in 3. Side effects, most commonly drowsiness, were similar

with both MS and DADL and suggest supraspinal effects by both drugs. At the doses given i.t. DADL

produced effective pain relief in patients tolerant to systemic opiates although no significant difference in

analgesic efficacy between MS and DADL was observed. Studies of the relative analgesic potency of i.t.

DADL in man are necessary to fully assess its value in those patients tolerant to systemic or i.t. opiates

SO - Pain 1985;23:213-221

UI - 000057

AU - Schmidt WK

AU - Tam SW

AU - Shotzberger GS

AU - Smith DH Jr.

AU - Clark R

AU - Vernier VG

TI - Nalbuphine. [Review]

AB - Nalbuphine is a potent analgesic with a low side effect and dependence profile in animals and man.

Nalbuphine is distinguished from other agonist/antagonist analgesics in having greater antagonist activity and

fewer behavioral effects at analgesic doses than pentazocine, butorphanol or buprenorphine. At equi-

analgesic doses, nalbuphine is quantitatively similar to nalorphine in regard to its large ratio of antagonist to

analgetic activity. Clinical studies have confirmed this balance of strong antagonist to analgesic activity.

Nalbuphine has been shown to effectively antagonize the respiratory depressant activity of narcotic

analgesics while concomitantly adding to their analgetic responses. Unlike nalorphine or pentazocine,

nalbuphine produces few overt behavioral or autonomic effects in animals at doses over 300 times its

analgesic range. These findings are confirmed by clinical results which show that nalbuphine produces few

psychotomimetic effects, even at elevated dose levels, in contrast to nalorphine or pentazocine. Nalbuphine

produces limited respiratory depression in animals and in man. Significant cardiovascular effects have not

been found. Nalbuphine was found to produce significantly less inhibition of gastrointestinal activity than any

of the clinically useful narcotic or agonist/antagonist analgesics tested in animals. Nalbuphine's analgetic

effects are reversed by naloxone doses similar to those which reverse nalorphine's agonist effects. Results in

this and other tests suggest that nalbuphine is primarily a kappa-agonist/mu-antagonist analgesic. Unlike

pentazocine or buprenorphine, nalbuphine does not suppress the narcotic abstinence syndrome in partly-

withdrawn morphine-dependent animals or man. Rather, due to nalbuphine's strong antagonist activity,

analgesic-range doses of nalbuphine severely exacerbate the withdrawal syndrome in partly-withdrawn mice,

monkeys and humans. Nalbuphine also precipitates a strong abstinence response in non-withdrawn

morphine-dependent animals and man. In post-addict humans, analgesic-range doses of nalbuphine are

perceived as minimally morphine-like, but higher doses are judged to be progressively more nalorphine-like

(i.e. dysphoric), which further limits nalbuphine's abuse potential in drug-seeking individuals. Primary

dependence studies have demonstrated that physical dependence is possible at high dose levels that produce

marked side effects. Other studies show that dependence is unlikely to be of significance within nalbuphine's

usual analgesic range. Six-month studies in patients with chronic pain have confirmed that analgesic

tolerance or physical dependence is uncommon.(ABSTRACT TRUNCATED AT 400 WORDS)

[References: 47]

SO - Drug & Alcohol Dependence 1985;14:339-362

UI - 000059

AU - Slattery PJ

AU - Boas RA

TI - Newer methods of delivery of opiates for relief of pain. [Review]

AB - Successful pain management using opiates requires both an analgesic with sufficient intrinsic activity

and an effective administration system. Most instances of unsatisfactory pain control, however, are due to

failure to achieve and maintain adequate blood concentrations of the chosen drug. Newer techniques of

administration aim to overcome this problem. Oral opiate therapy with conventional or sustained-release

formulations of morphine provide good control of terminal cancer pain provided that a regular dosing

pattern is established and reviewed according to the patient's needs. This represents a significant departure

from the traditional 'as required' prescription of this type of drug. In the management of acute severe pain,

sublingual and intravenous opiates--self-administered as needed, or given by mandatory dosing schedules--

have also been shown to overcome the limitations of intermittent intramuscular injections. A further novel

development, stemming from basic neuroscience research, is the selective application of opiates to the spinal

cord via the epidural or intrathecal route. This controversial technique has led to major improvements in

treatment of some types of acute and chronic pain. [References: 61]

SO - Drugs 1985;30:539-551

UI - 000061

AU - Young RF

AU - Kroening R

AU - Fulton W

AU - Feldman RA

AU - Chambi I

TI - Electrical stimulation of the brain in treatment of chronic pain. Experience over 5 years

AB - Forty-eight patients underwent electrical stimulation of the brain for treatment of chronic pain

between 1978 and 1983. Average pain duration prior to treatment was 4.5 years. Before selection for this

procedure patients underwent pain treatment in a multidisciplinary pain center, intensive psychological and

psychiatric evaluation, and assessment of pain responsiveness to intravenous administration of placebo,

morphine, and naloxone. A total of 71 electrodes were placed in the 48 patients at a variety of stimulating

targets, including the periaqueductal gray matter, periventricular gray matter, thalamus, and internal capsule.

Seventy-two percent of patients experienced complete or partial pain relief. In addition, 59% of patients

were able to discontinue narcotic usage. Twenty-five percent of patients returned to normal physical

activities and another 33% showed marked improvement in functional capacity. Follow-up periods ranged

from 2 to 60 months; with a mean follow-up period of 20 months. A variety of relatively minor

complications occurred, but no mortality or permanent sequelae were experienced. No patient's pain was

made worse as a result of electrical stimulation. Electrical stimulation of the brain offers a safe and relatively

effective method for the treatment of chronic pain in appropriately selected patients, who are unresponsive

to other forms of therapy

SO - Journal of Neurosurgery 1985;62:389-396

UI - 000177

AU - Zenz M

AU - Piepenbrock S

AU - Tryba M

TI - Epidural opiates: long-term experiences in cancer pain

AB - Epidural opiates were administered to 139 patients with pain due to malignant diseases via a chronic

indwelling catheter inserted percutaneously. So far, 9,716 days of treatment can be evaluated. In 87% of the

patients whose pain previously could not be controlled with conventional analgesic approaches, epidural

opiates resulted in remarkable pain relief. With a mean daily dose of 15.6 mg morphine (range 2-290 mg) or

0.86 mg buprenorphine (range 0.15-7.2 mg) half of the patients could be treated as outpatients. The mean

duration of therapy was 72 days (range 1-700 days), 26 catheters being in place for more than 100 days and

one catheter being in place for 510 days. Two severe side-effects (meningitis) were observed, both patients

being free of symptoms after catheter removal and antibiotic therapy. Epidural opiates proved to be a

valuable method of pain control in terminal illness. The method should be reserved for those patients, for

whom oral opiates fail to produce effective pain relief

SO - Klinische Wochenschrift 1985;63:225-229

UI - 000214

AU - Cohen SR

AU - Abbott FV

AU - Melzack R

TI - Unilateral analgesia produced by intraventricular morphine

AB - AB - Morphine injected into the lateral ventricle of the rat produced unilateral analgesia in the

formalin test, which involves continuous, moderate pain. In contrast, analgesia was produced bilaterally in

the foot-flick test which involves brief, rapidly rising pain. In the formalin test, intraventricular morphine

produced analgesia in the ipsilateral but not the contralateral hindpaw. Analgesia was achieved with

relatively low doses of morphine (2.5-10.0 micrograms) in the formation test while very high doses (50-200

micrograms) were necessary to produce analgesia in the foot-flick test. These results add to other data

indicating that different neural mechanisms underlie opiate analgesia in different types of pain. Moreover,

they indicate that, in the formation test, the neural mechanisms of morphine analgesia are somatotopically

organized and that forebrain structures are likely to be involved UI - 84258471

SO - Brain Res 1984;303:277-287

Return-Path: <tanante@mail.nwlink.com>

Comments: Authenticated sender is <tanante@mail.nwlink.com>

From: tanante@nwlink.com

To: schaffer@smartlink.net

Date: Sat, 1 Jun 1996 17:18:59 +0000

Subject: Re: Pain Medication #1

Priority: normal

UI - 000250

AU - France RD

AU - Urban BJ

AU - Keefe FJ

TI - Long-term use of narcotic analgesics in chronic pain

AB - AB - The use of narcotic analgesics have been avoided by clinicians in patients with chronic pain

syndromes. Uncertainty as to the etiological cause of chronic pain, development of addiction and habituation

and associated psychological and behavioral symptoms found in chronic pain states which are not amenable

to narcotic medications are the major reasons narcotics are not prescribed. This communication describes the

long-term use of low dose narcotic analgesics as a treatment component of a comprehensive pain

management program and addresses the questions of whether or not narcotic efficacy is maintained in long-

term use, improvement of patients' function is continued and side effects develop as a result of this treatment

UI - 85168356

SO - Soc Sci Med 1984;19:1379-1382

UI - 000243

AU - Rawson RA

AU - Tennant FS Jr.

TI - Five-year follow-up of opiate addicts with naltrexone and behavior therapy

AB - AB - A group of 58 heroin addicts were treated with naltrexone and behavior therapy and followed

for 5 years. At one-year post-treatment, almost half of the naltrexone-treated subjects were opiate free.

Follow-up results at 5 years post-treatment indicate that over 90% of those patients treated with naltrexone

became re-addicted for various periods of time. However, naltrexone-treated subjects did feel their treatment

with naltrexone had provided them with the ability to remain opiate free for blocks of time. The results

suggest that naltrexone is not a "cure" for opiate dependence, but is a medication which can be useful in

protecting patients from re- addiction and is a modality patients should be encouraged to return to if they

feel vulnerable to re-addiction UI - 85012611

SO - NIDA Res Monogr 1984;49:289-295

UI - 000228

AU - Tennant FS Jr.

AU - Rawson RA

AU - Cohen AJ

AU - Mann A

TI - Clinical experience with naltrexone in suburban opioid addicts

AB - AB - In a study of 160 patients (including 114 active heroin addicts and 42 former heroin addicts

maintained on methadone, propoxyphene napsylate, or LAAM), subjects were retained on treatment with

naltrexone for a mean of 50.7 days (range, 1-635). Clonidine or guanabenz acetate was used to detoxify

subjects who received naltrexone within 10 days of their last dose of opioid. Because of the number of

subjects dropping out of treatment after only a few days, it is recommended that there be an opioid-free

period of 5 or more days for heroin-dependent subjects and 10 or more days for those on medical

maintenance. A naloxone challenge should be administered at a dosage of 0.8 mg. Use of naltrexone

combined with psychotherapy appears to promote long periods of opioid abstinence but does not prevent

relapse after treatment. Trained clinicians utilizing an appropriate induction protocol can effectively treat

volunteer opioid addicts with naltrexone UI - 84289325

SO - J Clin Psychiatry 1984;45:42-45

UI - 000242

AU - Tennant FS Jr.

AU - Rawson RA

TI - Guanabenz acetate: a new, long-acting alpha-two adrenergic agonist for opioid withdrawal

AB - AB - Guanabenz Acetate (GA) is a new long-lasting alpha-two agonist. We found that it effectively

suppressed opioid withdrawal in the majority of 47 opioid-dependent subjects. GA was usually given in

twice per day dosages and did not appear to have as many side effects as clonidine. It may have greater

acceptance among heroin addicts than clonidine UI - 85012622

SO - NIDA Res Monogr 1984;49:338-343

UI - 000002

AU - Woody GE

AU - McLellan AT

AU - O'Brien CP

TI - Treatment of behavioral and psychiatric problems associated with opiate dependence

AB - IN: Philadelphia VA Medical Ctr, PA LA: English AB: Discusses behavioral and psychiatric problems

associated with opiate dependence and its treatment, noting that diverse medical, behavioral, and psychiatric

problems interact to produce constellations of complex disorders in opiate addicts. Previous research has

identified depression as the most common disorder, followed by alcoholism, antisocial personality, anxiety,

schizophrenia, mania, and hypomania. Other situational reactions involve intense anger, psychiatric disorders

complicated by medical conditions (e.g., hepatitis), and illnesses or injuries producing chronic pain (e.g.,

pancreatitis, sickle cell anemia, nerve root irritation). Loitering is also a behavioral problem due to drug

dealing that occurs when patients loiter. Management and orientation of these problems from a practical

perspective are discussed, and it is asserted that it is essential for drug treatment programs to place a high

priority on problem control, which is best accomplished through consistent enforcement of rules. Further

recommendations are presented with regard to staffing, policies, physical facilities, diagnosis and treatment,

and research and clinical efforts. (4 ref) (PsycLIT Database Copyright 1984 American Psychological Assn,

all rights reserved) KP: treatment of behavioral & psychiatric problems associated with opiate dependence

AN: 71-32471

SO - National Institute on Drug Abuse Research Monograph Series 1984;:1984 Mono 46 23-1984 Mono

46 35

UI - 000180

AU - Zenz M

TI - Spinal opiate analgesia. [German]

AB - The spinal application of opiates is followed by a long-lasting and strong pain relief. This action is

based upon the binding of opiates to specific opiate receptors situated in the substantia gelatinosa of the

spinal cord. Two possible approaches exist -intrathecally or epidurally. The intrathecal opiate analgesia is

combined with a very high incidence of side effects, so that this way cannot be recommended. The epidural

opiate analgesia has proven good results with few side effects in the treatment of postoperative pain, pain of

multiple rib fractures and other thoracic trauma or cancer pain. In obstetrics analgesia by spinal opiates was

disappointing. Mode of action, possible side effects and the results of epidural opiates are discussed

SO - Arzneimittel-Forschung 1984;34:1089-1092

UI - 000181

AU - Zenz M

TI - Epidural opiates for the treatment of cancer pain

SO - Recent Results in Cancer Research 1984;89:107-114

UI - 000001

AU - Atkinson JH

AU - Kremer EF

AU - Risch SC

AU - Bloom FE

TI - Neuroendocrine function and endogenous opioid peptide systems in chronic pain

AB - IN: U California-San Diego, School of Medicine, La Jolla LA: English AB: Reviews the literature on

neuroendocrine abnormalities in patients with chronic pain syndrome, with an emphasis on evidence in this

population of (a) failure to suppress plasma cortisol concentration in the low-dose dexamethasone

suppression test (DST) and (b) elevated opioid peptide immunoreactivity. 24 chronic pain patients (aged 32-

82 yrs) were administered the DST, the Beck Depression Inventory, and the Hamilton Rating Scale for

Depression. Results suggest that endogenous opioid peptide system disfunction and neuroendocrine

abnormalities occur regularly in chronic pain patients. It is concluded that further study of the DST could

lead to its being of predictive value for responses to behavioral intervention or pharmacologic treatment. (31

ref) (PsycLIT Database Copyright 1985 American Psychological Assn, all rights reserved) KP: endogenous

opioid peptide system dysfunction & neuroendocrine abnormalities; 32-82 yr old chronic pain patients AN:


SO - Psychosomatics 1983;24:899-913

UI - 000003

AU - Cohen MR

AU - Pickar D

AU - Dubois M

TI - The role of the endogenous opioid system in the human stress response

AB - IN: NIMH Clinical Neuroscience Branch, Section on Clinical Studies, Bethesda, MD LA: English AB:

Reviews the utilized strategies and the status of experimental work on the involvement of the endogenous

opioid system (EOS) in human adaptation to stressors. Three principal research strategies have been used:

(1) measurement of endorphin levels in body fluids (CSF and plasma) in relationship to the stress response

and the evaluation of effects on the stress response, (2) enhancement of the functioning of the EOS by

administering an opioid agonist, and (3) suppression of the functioning of the EOS by the administration of

an opioid antagonist (principally naloxone). Clinical studies with humans have demonstrated some stress-

induced analgesia, increased plasma levels of beta-endorphin after demanding physical exercise and in later

stages of labor, and decreases in lumbar CSF opioid levels in Ss suffering from chronic pain. In surgical

studies, evidence was found that elevated plasma beta-endorphin levels may be considered a biologic marker

of the human stress response. In addition, alterations in the physiological response to surgical stress followed

administration of opiates, suggesting the potential of the EOS to modify stress responses. (75 ref) (PsycLIT

Database Copyright 1984 American Psychological Assn, all rights reserved) KP: endogenous opioids; stress

responses; humans; literature review AN: 71-28038

SO - Psychiatric Clinics of North America 1983;6:457-471

UI - 000212

AU - Dennis SG

AU - Melzack R

TI - Effects of cholinergic and dopaminergic agents on pain and morphine analgesia measured by three pain


AB - AB - The effects of several cholinergic and dopaminergic agents on pain and morphine analgesia were

assessed using three pain tests. These tests--tail-flick, hot-plate, and Formalin--allow comparison of the

effects of different noxious stimuli and different motor responses. Each pain test yielded a unique

constellation of cholinergic and dopaminergic influences, suggesting that variation of stimulus and response

parameters can change the functional expression of cholinergic and dopaminergic systems related to pain

processing. Significant analgesia was observed in the Formalin test, compared with the saline control, after

administration of choline (30 or 60 mg/kg), atropine (2 mg/kg), mecamylamine (2 mg/kg or 10 mg/kg), or

apomorphine (0.3 or 8 mg/kg). No analgesic effects in this test were observed after atropine (10 mg/kg) or

pimozide (0.125 or 0.5 mg/kg). In contrast, there was no evidence of analgesia produced by any of these

drugs, in the doses given, in the hot-plate test, and only apomorphine (8 mg/kg) produced analgesia in the

tail-flick test. When these cholinergic and dopaminergic agents were administered to rats after an injection of

2.5 mg/kg morphine, which by itself has been shown not to produce analgesia in any of the tests, a general

pattern of facilitation was observed in the Formalin test but not in the tail- flick or hot-plate tests. Facilitation

was produced by choline, atropine, mecamylamine, apomorphine, and pimozide (at 0.5 mg/kg but not 0.125

mg/kg). The data suggest that differences in the type of noxious stimulation and in the motor responses

required in various pain tests are crucial in determining the observed pharmacologic profile of pain and

opiate analgesia UI - 83234877

SO - Exp Neurol 1983;81:167-176

UI - 000005

AU - Freeman TB

AU - Campbell JN

AU - Long DM

TI - Naloxone does not affect pain relief induced by electrical stimulation in man

AB - IN: New York U Medical Ctr, Dept of Neurosurgery LA: English AB: Investigated whether pain

relief that resulted from transcutaneous (TNS) or spinal cord electrical stimulation in patients with chronic

pain was due to activation of an endogenous opiate-related pain control system. Naloxone (0.4-10 mg, iv) or

saline was injected in double-blind fashion into opiate-naive Ss with chronic pain who achieved 30% or

greater pain relief with spinal cord stimulation (4 patients) or TNS (9 patients). Ss (aged 14-62 yrs) rated

their pain during stimulation and 2, 5, 10, and 15 min after the injection. Two days or more later the

procedure was repeated using the alternate agent (naloxone or saline). Naloxone did not decrease the pain

relief induced by stimulation, suggesting that the effects of stimulation are probably not mediated by the

endogenous opiates. (27 ref) (PsycLIT Database Copyright 1984 American Psychological Assn, all rights

reserved) KP: naloxone; pain relief resulting from transcutaneous or spinal cord electrical stimulation;

chronic pain patients; implications for non-opiate mechanisms in pain control AN: 71-20982

SO - Pain 1983;17:189-195

UI - 000006

AU - Gillman MA

AU - Lichtigfeld FJ

TI - "Naloxone fails to antagonize nitrous oxide analgesia for clinical pain": Comment

AB - LA: English AB: Contends that the claim of J. D. Levine et al (see PA, Vol 69:6297) that their

investigation is the first in which the effect of naloxone N-sub-2O analgesia was tested in clinical pain is

unfounded since the present authors (1981) had previously conducted a study of chronic pain patients. The

present authors have also developed a hypothesis to explain the paradoxical effects of naloxone on the basis

of a dual system involving both opiate and anti-opiate actions. (9 ref) (PsycLIT Database Copyright 1984

American Psychological Assn, all rights reserved) KP: naloxone; nitrous oxide-induced analgesia; chronic

pain patients; comments on research of J. D. Levine et al AN: 71-18416

SO - Pain 1983;17:103-104

UI - 000178

AU - Piepenbrock S

AU - Zenz M

AU - Gorus R

AU - Link J

AU - Reinhart K

TI - Buprenorphine and pentazocine for postoperative analgesia. A double blind study following abdominal

surgery. [German]

AB - A randomized double-blind study was done to test the two opiates buprenorphine (0.3 mg i.v.) and

pentazocine (30 mg i.v.) with regard to their applicability for the postoperative phase. These substances

were chosen because they are not subject to drug prescription regulations. 60 patients who had undergone

epigastric and hypogastric interventions under thiopental-sodium-induced halothane anesthesia received i.v.

injections of one of the two analgetics as soon as they requested a pain-killer postoperatively. The subjective

pain intensity registered by means of a visual analogue scale shows a gradual decrease after buprenorphine

with maximal effects 1-3 h post injectionem (7.3 leads to 1.5). The duration of action is 8.2 +/- 0.7 h on the

average (median 8 h; range 4-22 h). The maximal analgetic effect of pentazocine is already attained after 10

min (6.3 leads to 3.2). Thereafter the pain-intensity curve rises again. Pentazocine has a mean duration of

action of 2.35 +/- 0.24 h (median 2 h; range 0.5-5 h). The inadequate analgetic effect of pentazocine

manifests itself in an only slight initial reduction of the respiratory rate (19.5 leads to 17.5 min-1), which, on

the other hand, decreases significantly and continuously under buprenorphine (20.8 leads to 13.5 min-1).

Both substances cause increases of PaCO2 (buprenorphine 37.3 leads to 46.8 mmHg; pentazocine 36.3 leads

to 43.0 mmHg), values greater than 50 mmHg being attained in individual cases.(ABSTRACT


SO - Anaesthesist 1983;32:601-609

UI - 000004

AU - Tennant FS

TI - (--)-a-Acetylmethadol for treatment of chronic pain patients who abuse opioids

AB - IN: U California Ctr for Health Science, School of Public Health, Los Angeles LA: English AB: Levo-

alpha-acetylmethadol (LAAM), an opioid with a duration of action up to 72 hrs, relieved pain and eliminated

abuse of opioids in 3 of 4 patients (aged 26-62 yrs) who had chronic pain secondary to permanent,

anatomical alterations. LAAM appears particularly suited to chronic pain patients who require opioid

analgesia but abuse opioids. (14 ref) (PsycLIT Database Copyright 1984 American Psychological Assn, all

rights reserved) KP: levo-alpha-acetylmethadol; 26-62 yr old chronic pain patients who abuse opioids AN:


SO - Drug and Alcohol Dependence 1983;12:243-247

UI - 000244

AU - Tennant FS Jr.

AU - Rawson RA

AU - Miranda L

AU - Obert J

TI - Outpatient treatment of prescription opioid dependence: comparison of two methods

AB - AB - Outpatient treatment of 42 patients who presented with dependence upon prescription opioids

was attempted by two different methods. The first group of 21 patients was treated by 21-day detoxification

followed by psychotherapeutic counseling (D/C), and the next 21 patients were offered 21-day detoxification

to be followed by opioid maintenance if detoxification was unsuccessful (D/M). Only 5 of 21 (23.8%)

patients in the D/C group compared to 20 of 21 (95.2%) in the D/M group completed three weeks of

treatment (P less than .001). On admission, no patient perceived that chronic pain due to a medical condition

would be an impediment to withdrawal from opioids, but pain which was masked by opioid dependency and

which emerged during detoxification proved to be an insurmountable barrier to total withdrawal in the

majority of patients. Treatment of outpatients who presented with dependence upon prescription opioids

was best provided in the study by opioid maintenance and adjunctive pain therapy UI - 83271438

SO - NIDA Res Monogr 1983;43:315-321

UI - 000235

AU - Tennant FS Jr.

TI - (-)-alpha-Acetylmethadol for treatment of chronic pain patients who abuse opioids

AB - AB - (-)-alpha-Acetylmethadol (LAAM) is an opioid with a duration of action up to 72 h. It appeared

to relieve pain and eliminate abuse of opioids in three of four patients who had chronic pain secondary to

permanent, anatomical alterations. LAAM may be very helpful in the treatment of many chronic pain patients

SO - Drug Alcohol Depend 1983;12:243-247

UI - 000183

AU - Twycross R

AU - Zenz M

TI - Use of oral morphine in incurable pain. [German]

AB - Oral morphine sulphate is the strong narcotic of choice at most hospices. Administered in simple

aqueous solution (e.g. 10 mg in 10 ml). No advantage in giving as "Brompton Cocktail." Usual starting dose

10 mg every 4 h. If patient has previously only had a weak narcotic analgesic, 5 mg may be adequate. If

changing to morphine from alternative strong narcotic, such as dextromoramide, levorphanol, methadone, a

considerably higher dose may be needed. With frail elderly patients, it may be wise to start on sub-optimal

dose in order to reduce likelihood of initial drowsiness and unsteadiness. Adjust upwards after first dose if

not more effective than previous medication. Adjust after 24 h "if pain not 90% controlled." Most patients

are satisfactorily controlled on dose of between 5 and 30 mg 4 hourly; however, some patients need higher

doses, occasionally up to 500 mg. Giving a larger dose at bedtime (1,5 or 2 x daytime dose) may enable a

patient to go through the night without waking in pain. Use co-analgesic medication as appropriate. Eigher

prescribe an antiemetic concurrently or supply (in anticipation) for regular use should nausea or vomiting

develop. Prescribe laxative. Adjust dose according to response. Suppositories may be necessary. Unless

carefully monitored, constipation may be more difficult to control than the pain. Write out regimen in detail

with times to be taken, names of drugs and amounts to be taken. Warn patient of possibility of initial

drowsiness. Arrange for close liaison and follow up

SO - Anaesthesist 1983;32:279-283

UI - 000182

AU - Zenz M

AU - Piepenbrock S

AU - Tryba M

AU - Bramswig H

TI - Peridural opiate analgesia. Clinical results of a 2-year study. [German]

AB - Postoperative pain relief, consumption of analgesics and the incidence of postoperative complications

were investigated in a retrospective cohort-study on 470 patients following abdominal surgery. 221 of these

patients received epidural morphine or buprenorphine for postoperative pain relief (Group I). Another group

of 249 patients received conventional opiate analgesics intravenously or intramuscularly (Group II). On

average the analgesia lasted 14 h after epidural morphine and 11 h after epidural buprenorphine. The overall

amount of morphine in the postoperative period was 13.3 +/- 14.9 mg and 0.89 +/- 0.55 mg buprenorphine

respectively. 5 cases of pneumonia (2.3%) were seen in the epidural group (Group I). 22 pneumonia cases

(8.8%) were registered in the group with conventional analgesics (Group II). Besides the advantage of

stronger and longer duration, small dosage and minor central depressive side effects, epidural opiate

analgesia has proven to result in positive clinical consequences. The low incidence of postoperative

pneumonia is due to the strong regional pain relief, which improves mechanical pulmonary function and gas


SO - Anaesthesist 1983;32:289-294

UI - 000179

AU - Zenz M

AU - Piepenbrock S

AU - Tryba M

AU - Klauke W

AU - Everlien M

TI - Sublingual buprenorphine tablets: initial clinical experiences in long-term therapy of cancer pain.


AB - Buprenorphine sublingual tablets (0.2 mg) were investigated in therapy of cancer pain. In 67 patients

there was a good analgetic effect in 60%, even in those cases treated with other opiates before. The

induction time was quite long (60 min.) but is no problem in chronic administration. Effective pain relief was

obtained even in final stages of cancer. The mean daily dose of buprenorphine had been 1.2-1.7 mg, the

mean duration of analgesia being 6-8 hours with a single dose of 0.2-1.0 mg buprenorphine. Typical opiate-

side-effects were registered and well tolerated after some days' treatment. There was no respiratory

depression. Buprenorphine sublingual tablets are certainly a good alternative in orally available opioids

SO - Fortschritte der Medizin 1983;101:191-194

UI - 000222

AU - Aronoff GM

TI - The use of non-narcotic drugs and other alternatives for analgesia as part of a comprehensive pain

management program

AB - AB - Chronic pain remains an enigma which mystifies the most experienced clinicians. The traditional

approaches to malignant pain employ narcotic analgesics, radiotherapy, surgical intervention, and

chemotherapy. Within the context of a "therapeutic community" oriented pain unit, we attack this major

public health problem differently. The use of non-narcotic analgesics, mood altering medications, various

forms of psychotherapy (individual, group, family, gestalt, psychomotor) and peer pressure when used in

conjunction with various physical modalities of treatment (including biofeedback, transcutaneous electrical

nerve stimulator, physical therapy, whirlpool, massage, ice, heat, etc.) appear most efficacious. Frequently,

the powerful tools of psychological medicine are taken for granted; yet, depression in the United States is

widespread and so significantly complicates medical illness that any treatment program designed for pain

patients must be holistic in its orientation if it is to be effective AD - Boston Pain Unit AD -Massachusetts

Rehabilitation Hospital AD - Boston AD - MA UI -83084453

SO - J Med 1982;13:191-202

UI - 000007

AU - Ehrenpreis S

TI - D-phenylalanine and other enkephalinase inhibitors as pharmacological agents: Implications for some

important therapeutic applications

AB - IN: University of the Health Sciences/Chicago Medical School LA: English AB: Dextrophenylalanine

has proven to be beneficial in many human patients with chronic, intractable pain and is anti-inflammatory as

well. It is suggested that the enkephalinase inhibitors may be effective in a number of human "endorphin

deficiency diseases" such as depression, schizophrenia, convulsive disorders, and arthritis. Such compounds

may alleviate other conditions associated with decreased endorphin levels, such as opiate withdrawal

symptoms. (57 ref) (PsycLIT Database Copyright 1984 American Psychological Assn, all rights reserved)

KP: dextrophenylalanine & enkephalinase inhibitors; treatment of chronic pain & endorphin deficiency

diseases & opiate withdrawal symptoms AN: 71-10228

SO - Acupuncture and Electro Therapeutics Research 1982;7:157-172

UI - 000008

AU - Hameroff SR

TI - Doxepin effects on chronic pain, depression and plasma opioids

AB - IN: U Arizona Health Science Ctr, Dept of Anesthesiology, Tucson LA: English AB: Studied 30 26-

65 yr old patients with chronic low back or cervical pain combined with clinical depression in a randomized,

double-blind comparison of doxepin and placebo. Dependent variables included Hamilton Rating Scale for

Depression (HDRS) scores; the Clinical Global Assessment Scale (CGAS); the Profile of Mood States

(POMS); and subjective ratings (visual analog scales) of pain severity, percent of time pain was felt, and

effect of pain on activity, muscle tension, sleep, mood, and analgesic consumption. Significant improvements

in the doxepin-treated group compared to the placebo group were seen in HDRS, CGAS, and POMS

scores; percent of time pain was felt; and effect of pain on sleep, muscle tension, and mood. Some

improvement was observed after 1 wk, although most improvement occurred at 6 wks, when the mean

doxepin dose was 2.5 mg/kg and plasma doxepin and desmethyldoxepin averaged 70 ng/ml. Nonspecific

enkephalinlike activity (but not beta-endorphins) increased for the treatment group and decreased for the

placebo group. Doxepin may be a valuable treatment for patients with chronic pain and depression. (12 ref)

(PsycLIT Database Copyright 1983 American Psychological Assn, all rights reserved) KP: doxepin;

treatment of low back or cervical pain combined with depression; 26-65 yr old patients AN: 69-06286

SO - Journal of Clinical Psychiatry 1982;43:22-27

UI - 000227

AU - Tennant FS Jr.

AU - Rawson RA

TI - Outpatient treatment of prescription opioid dependence: comparison of two methods

AB - AB - Twenty-one patients dependent on prescription opioids were treated by 21-day detoxification

followed by psychotherapeutic counseling (D/C), and 21 patients were detoxified 21 days and provided

opioid maintenance if detoxification was unsuccessful (D/M). Only five of 21 (23.8%) patients in the D/C

group compared with 20 of 21 (95.2%) in the D/M group completed three weeks of treatment. No patient

initially perceived that chronic pain due to a medical condition would be an impediment to withdrawal from

opioids, but pain that was masked by opioid dependency and that emerged during detoxification proved to

be an insurmountable barrier to total withdrawal in the majority of patients. Treatment of outpatients with

dependence on prescription opioids is best provided by opioid maintenance therapy and adjunctive pain

therapy UI - 83021493

SO - Arch Intern Med 1982;142:1845-1847

UI - 000245

AU - Tennant FS Jr.

AU - Rawson RA

TI - Propoxyphene napsylate maintenance treatment of narcotic dependence: use of a non-methadone model

AB - AB - One hundred seventy-eight (178) heroin addicts entered propoxyphene napsylate (PN)

maintenance. Patients attended a general medical clinic two times each week and took home a three-to four-

day supply of PN which was usually taken in doses of 300 to 400 mg three to four times per day. Over a 21-

month period, the subjects entered and re- entered PN treatment 166 times (1.5 times per patient) and

remained a mean of 10.6 weeks per treatment. A comparison with a group of methadone maintenance

patients indicated similar performance in employment and heroin use. The ability to take PN, attend a clinic

less often than daily, and discontinue and re-enter treatment on a discretionary basis is preferred treatment

approach for some narcotic addicts UI - 83012906

SO - NIDA Res Monogr 1982;41:246-252

UI - 000009

AU - Jorum E

TI - Endogene opiater og deres rolle i smerte-opplevelsen. (Endogenous opiates' role in pain perception.)

AB - IN: U Oslo, Nevrofysiologisk Inst, Norway LA: Norwegian AB: The recent discovery of morphine-

like substances and their receptors in the CNS has resulted in further understanding of the complex

phenomenon of pain. The endogenous opiates--the enkephalins and endorphins--are richly presented in brain

structures involved in pain perception and emotional behavior. The physiological part played by these

opiates seems to be pain relief in situations of fear and anxiety. Disturbances in the endogenous level of

endorphins and enkephalins may result in chronic pain and psychiatric disorders. Acupuncture analgesia is

produced by a rise in the brain level of opiates, most likely the endorphins, further activating the descending

midline serotonin system from the raphe nuclei known to exert inhibitory effects on spinal pain transmission.

(5 ref) (PsycLIT Database Copyright 1982 American Psychological Assn, all rights reserved) KP:

endogenous opiates; pain perception AN: 68-00559

SO - Tidsskrift for Norsk Psykologforening 1981;18:565-570

UI - 000247

AU - Rawson RA

AU - Washton AM

AU - Resnick RB

AU - Tennant FS Jr.

TI - Clonidine hydrochloride detoxification from methadone treatments: the value of naltrexone aftercare

AB - AB - [No Abstract Available] UI - 81172979

SO - NIDA Res Monogr 1981;34:101-108

UI - 000236

AU - Tennant FS Jr.

AU - Rawson RA

TI - Propoxyphene napsylate maintenance treatment for narcotic dependence: a non-methadone model

AB - AB - One hundred and seventy eight heroin addicts entered propoxyphene napsylate (PN)

maintenance. Patients attended a general medical clinic twice each week and took home a three- to four-day

supply of PN, to be taken in doses of 300 to 400 mg three or four times per day. Over a 21-month period,

subjects entered and re-entered PN treatment 266 times (1.5 times per patient) and remained in treatment a

mean of 10.6 weeks. When compared with a group of methadone maintenance patients, similar

characteristics in employment and heroin use were found. The ability to take PN, attend a clinic less often

than daily and discontinue and re-enter treatment on a discretionary basis is a preferred treatment approach

for some narcotic addicts UI -82050191

SO - Drug Alcohol Depend 1981;8:79-83

UI - 000246

AU - Tennant FS Jr.

TI - The California registration system for habitues to schedule II drugs

AB - AB - In order to help control abuse and prevent over-prescribing, California has developed triplicate

prescriptions for Schedule II narcotics as well as a system for physicians to publicly register patients who are

habitues to Schedule II Controlled Substances. A preliminary evaluation indicates that there is under-

reporting and confusion among physicians about the system, but it has probably helped control Schedule II

narcotic abuse in California while not depriving patients of needed treatment. Physicians appear to prescribe

Schedule II narcotics for serious medical conditions but may underprescribe narcotics for some chronic pain

patients and subject others to potential complications of high, chronic doses or oral narcotics which are

combined with salicylate, acetaminophen, or phenacetin. Despite some defects, California's system of

triplicate prescriptions and public registration of habitues appears a viable alternative to the removal of

abusable, Schedule II drugs from the commercial market UI - 81172994

SO - NIDA Res Monogr 1981;34:193-198

UI - 000184

AU - Zenz M

TI - Peridural opiate analgesia. [German]

SO - Deutsche Medizinische Wochenschrift 1981;106:483-485

UI - 000257

AU - Porter J

AU - Jick H

TI - Addiction Rare in Patients Treated With Narcotics

AB - ABSTRACT: In a survey of 11,882 patients receiving narcotics, only 4 documented cases of

addiction. TPH 4/28/94

SO - N Engl J Med 1980;302:123-123

UI - 000256

AU - Porter J

AU - Jick H

TI - Addiction rare in patients treated with narcotics [letter]

AB - AB - [No Abstract Available] UI - 80077926

SO - N Engl J Med 1980;302:123-123

UI - 000232

AU - Tennant FS Jr.

AU - Uelmen GF

TI - Prescribing narcotics to habitual and addicted narcotic users. Medical and legal guidelines in California

and some other Western states

AB - AB - [No Abstract Available] UI - 81128307

SO - West J Med 1980;133:539-545

UI - 000241

AU - Tennant FS Jr.

TI - Physician extender protocols for urgent situations in drug and alcohol clinics

AB - AB - [No Abstract Available] UI - 80251766

SO - J Psychedelic Drugs 1979;11:211-215

UI - 000013

AU - Akil H

AU - Watson SJ

AU - Sullivan S

AU - Barchas JD

TI - Enkephalin-like material in normal human CSF: Measurement and levels

AB - IN: Stanford U School of Medicine, Nancy Pritzker Lab of Behavioral Neurochemistry LA: English

AB: Identified an opioid substance in lumbar cerebrospinal fluid (CSF) that appears to resemble methionine-

enkephalin in its behavior in 2 chromatographic systems. Ss were 10 normal 19-28 yr old males and 5 Ss

with chronic intractable pain who were undergoing a neurosurgical procedure for the alleviation of that pain.

The substance appears to interact with the opiate receptor assay and with a methionine-enkephalin

radioimmunoassay. While this material resembles enkephalin, it could not be identified as such with the

techniques employed in the present study. (9 ref) (PsycLIT Database Copyright 1979 American

Psychological Assn, all rights reserved) KP: identification & measurement of enkephalin-like material in

cerebrospinal fluid; 19-28 yr old males & Ss with chronic pain AN: 62-13062

SO - Life Sciences 1978;23:121-125

UI - 000012

AU - Almay BG

TI - Endorphins in chronic pain: I. Differences in CSF endorphin levels between organic and psychogenic

pain syndromes

AB - IN: U Umea, Sweden LA: English AB: Investigated neurologic and psychiatric variables in 37 patients

with chronic pain. 20 Ss were classified as having mainly organic (i.e., somatogenic) pain syndromes, while

17 Ss were suffering from psychogenic pain syndromes. Samples of lumbar cerebrospinal fluid (CSF) were

obtained from the Ss and analyzed for the presence of opiate receptor-active material, here called

endorphins. Ss classified as having mainly organic pain syndromes were found to have significantly lower

endorphin levels than Ss with predominantly psychogenic pain syndromes. In the total group of Ss as well as

in the 2 subgroups, there was a significant correlation between CSF endorphin levels and the depth of

depressive symptomatology as reported by the patients. On the other hand, there was no correlation between

CSF endorphin levels and extent of anxiety or motor retardation. It is concluded that CSF endorphins reflect

central processes involved in chronic pain syndromes. (28 ref) (PsycLIT Database Copyright 1980 American

Psychological Assn, all rights reserved) KP: cerebrospinal fluid levels of endorphins & depressive

symptomatology & anxiety & motor retardation; patients with chronic pain of somatogenic vs psychogenic

origin AN: 63-01246

SO - Pain 1978;5:153-162

UI - 000238

AU - Beckett GE

AU - Tennant FS Jr.

TI - Coordination of institution and parole services: an innovation within California's Civil Addict Program

AB - AB - Parole outcome was measured 1 year after release of 397 narcotic addicts processed by an

experimental program in which both institution and parole services were administered together. Conparison

of outcome of this group to the outcome of 361 traditionally processed addicts revealed a positive effect on

parole outcome of violators (those with prior parole experience) compared to new commitments (p less than

.05). This was particularly true for the community parole unit which made most use of community resources

(p less than .05). Community adjustment of some narcotic addicts may be increased by administrative

interdependence and by optimal use of other community resources. The future for such programs seems

brightest at the local level of government UI - 78150140

SO - Int J Addict 1978;13:249-256

UI - 000224

AU - Brodner RA

AU - Taub A

TI - Chronic pain exacerbated by long-term narcotic use in patients with nonmalignant disease: clinical

syndrome and treatment

AB - AB - [No Abstract Available] UI - 78199525

SO - Mt Sinai J Med 1978;45:233-237

UI - 000010

AU - Kerr FW

AU - Wilson PR

TI - Pain

AB - IN: Mayo Clinic & Foundation, Rochester, MN LA: English AB: Reviews recent contributions

towards understanding pain mechanisms, including stimulus-produced analgesia, identification of the opiate

receptor, elucidation of the mechanisms and sites of action of morphine analgesia, and the discovery and

characterization of an entirely new endogenous analgesic system. The literature cited deals primarily with

animal research, but the application of these findings to human investigations and to medical procedures

(such as dorsal rhizotomy and cordotomy) is also considered. The lack of an acceptable animal model for

human chronic pain is noted. The authors theorize that pain is mediated via a specific system that is

particularly sensitive to noxious stimuli. However, pain control as an ultimate research goal is still elusive.

(51/2 p ref) (PsycLIT Database Copyright 1980 American Psychological Assn, all rights reserved) KP: role

of stimulus produced analgesia & identification of endogenous opiate receptors & mechanisms & sites of

action of morphine analgesia in understanding of pain mechanisms; literature review AN: 64-02761

SO - Annual Review of Neuroscience 1978;1:83-102

UI - 000213

AU - Mount BM

AU - Melzack R

AU - MacKinnon KJ

TI - The management of intractable pain in patients with advanced malignant disease

AB - AB - The Brompton mixture is a highly effective, flexible, safe and convenient means to control

chronic pain of malignant disease. The mixture is a solution containing morphine, the dose of narcotic

varying with the need for analgesia, and is given regularly, usually every 4 hours, with a phenothiazine. The

main aims of therapy are prevention of pain rather than treatment, an unclouded sensorium and a normal

effect. Terminally ill cancer patients were given the Brompton mixture and a phenothiazine in an attempt to

control their pain. The mixture was administered to patients in 3 hospital environments: 1) a palliative care

unit, 2) general wards and 3) private rooms. Pain was measured in 92 patients with the McGill- Melzack

pain questionnaire. The Brompton mixture controlled pain in 90 per cent of patients in the palliative care unit

and in 75 to 80 per cent of patients in the wards or private rooms. The differences in pain scores between

patients in the palliative care unit and the other groups were significant. The mixture produced substantial

decreases in the 3 major dimensions of pain: 1) sensory, 2) affective and 3) evaluative. Comparison of these

results with data obtained in an outpatient pain clinic showed that the Brompton mixture was strikingly more

effective than the traditional methods of managing cancer pain UI - 79091506

SO - J Urol 1978;120:720-725

UI - 000011

AU - Villet B

TI - Opiates of the mind: The biggest medical discovery since penicillin

AB - LA: English AB: Surveys the progress in the field of neuropharmacology since the 1950s, including

the development or discovery of chlorpromazine, monoamine neurotransmitters, ACTH, enkephalins, and

endorphins. The roles of mitochondria, cell membranes, and the pituitary gland are mentioned. Beta

endorphin's action as a biochemical switch is described, as are the results of its use on animals and humans

for chronic pain, narcotic addiction, schizophrenia, depression, and agoraphobia. Presently, endorphins

represent the most promising area of research for the treatment of many diseases. (PsycLIT Database

Copyright 1980 American Psychological Assn, all rights reserved) KP: progress in neuropharmacology since

1950; use of endorphins for pain & narcotic addiction & mental disorders AN: 63-09307

SO - Atlantic Monthly 1978;241:82-89

UI - 000219

AU - Halpern LM

TI - Analgesic drugs in the management of pain

AB - AB - The use of potent narcotics to control severe pain should be of short duration and limited to

patients with acute diseases or inoperable or metastatic cancer who require long-term relief. Continued and

prolonged use of narcotics in patients with chronic benign pain is not recommended because of serious

behavioral consequences, the development of tolerance, and addiction liability. Long-term use of analgesic

drugs in chronic pain usually produces negative behavioral complications that are more difficult to manage

than the pain it was desired to eliminate. The use of antidepressant drugs in the pain regimen has been found

to provide increased relief of pain and often allows the dose of narcotic analgesic to be reduced or totally

eliminated UI - 77220872

SO - Arch Surg 1977;112:861-869

UI - 000218

AU - Mount BM

AU - Melzack R

AU - MacKinnon KJ

TI - The management of intractable pain in patients with advanced malignant disease

AB - AB - The Brompton mixture is a highly effective, flexible, safe and convenient means to control

chronic pain of malignant disease. The mixture is a solution containing morphine, the dose of narcotic

varying with the need for analgesia, and is given regularly, usually every 4 hours, with a phenothiazine. The

main aims of therapy are prevention of pain rather than treatment, an unclouded sensorium and a normal

effect. Terminally ill cancer patients were given the Brompton mixture and a phenothiazine in an attempt to

control their pain. The mixture was administered to patients in 3 hospital environments: 1) a palliative care

unit, 2) general wards and 3) private rooms. Pain was measured in 92 patients with the McGill- Melzack

pain questionnaire. The Brompton mixture controlled pain in 90 per cent of patients in the palliative care unit

and in 75 to 80 per cent of patients in the wards or private rooms. The differences in pain scores between

patients in the palliative care unit and the other groups were significant. The mixture produced substantial

decreases in the 3 major dimensions of pain: 1) sensory, 2) affective and 3) evaluative. Comparison of these

results with data obtained in an outpatient pain clinic showed that the Brompton mixture was strikingly more

effective than the traditional methods of managing cancer pain UI - 79119156

SO - Trans Am Assoc Genitourin Surg 1977;69:84-91

UI - 000014

AU - Omura Y

TI - Patho-physiology of acupuncture effects, ACTH and morphine-like substances, pain, phantom

sensations (phantom pain, itch and coldness), brain micro-circulation, and memory

AB - IN: Heart Disease Research Foundation, New York, NY LA: English AB: Suggests that, although

acupuncture is being gradually integrated by many US physicians into their daily practice of medicine, other

scientists, physicians, and academicians are still claiming that acupuncture has no scientific basis or is only a

form of hypnosis. A narrow approach to acupuncture research limits itself to study of the nervous system,

although there are equally important effects in the circulatory and endocrine systems. Previous research by

the author has shown that acupuncture effects on the microcirculatory system can normally be classified into

3 consecutively changing phases: vasoconstriction, quasi-control, and vasodilation of capillaries and

arterioles. Vasodilation effects are often accompanied by significant blood chemistry and complete blood

count changes, most of which resemble ACTH effects. Changes such as generalized vasodilation effects can

give various degrees of improvement in insomnia, irritability, impaired learning, memory, and brain

circulation. Pain threshold to electrical stimulation is often enhanced by acupuncture in the acupunctured

area, without respiratory depressant effect characteristics of opiates. The author proposes a concept of

"coded stored memory molecules" for chronic pain and phantom sensation, using examples of phantom pain,

phantom itch, and phantom coldness. The interrelationship of the effects of morphine derivaties and their

analogs and antagonists and acupuncture is discussed. (French & German abstracts) (40 ref) (PsycLIT

Database Copyright 1979 American Psychological Assn, all rights reserved) KP: molecular memory codes

for chronic & phantom pain; role of acupuncture & ACTH & morphine derivatives in pain reduction AN:


SO - Acupuncture and Electro Therapeutics Research 1977;2:1-31

UI - 000233

AU - Tennant FS Jr.

AU - Krantz KD

AU - Dobrin EI

TI - Use of difenoximide (SC-26100) for narcotic detoxification: a preliminary tolerance and efficacy study

AB - AB - Difenoximide (SC-26100) is closely related to the antidiarrheal agent, diphenoxylate, which is a

chemical congener of meperidine. It has been shown to have a greater ability than methadone to suppress

opiate withdrawal in addicted mice, and it has produced less physical dependence than morphine and

methadone in laboratory animals. In this study difenoximide was administered to nine active heroin addicts.

A dose of 4 mg administered 4 times per day for 3 days effectively suppressed opiate withdrawal, while a

dose of 8 mg produced symptoms resembling those of narcotic excess in subjects who had recently self-

administered heroin. No side effect were observed at the therapeutic dosage level, and the drug was well

accepted by subjects. Difenoximide was shown to be a potentially useful narcotic treatment agent in this

impatient study UI - 78163354

SO - Am J Drug Alcohol Abuse 1977;4:123-135

UI - 000249

AU - Tennant FS Jr.

AU - Detels R

TI - Relationship of alcohol, cigarette, and drug abuse in adulthood with alcohol, cigarette and coffee

consumption in childhood

AB - AB - [No Abstract Available] UI - 76176338

SO - Prev Med 1976;5:70-77

UI - 000237

AU - Tennant FS Jr.

AU - Tate JA

AU - Ruckel E

TI - Clinical trial in post-addicts with oxilorphan (levo-BC-2605): a new narcotic antagonist

AB - AB - Oxilorphan (levo-BC-2605) is a new, long-acting, narcotic antagonist that has agonist

properties. Twenty-one (21) heroin addicts in Los Angeles were detoxified and given at least one oral dose

of oxilorphan. Only three (14.3%) patients took daily doses for 14 days, which was the maximal time

allowed for oxilorphan administration in this study. The remainder discontinued oxilorphan because of

subjective side effects or for unknown reasons. Side effects most responsible for dropouts were dysphoria,

insomnia, weakness, hallucinations, nausea, drowsiness and anorexia. Oxilorphan provided 24-hour

protection with a single, oral dose, but subjective side effects encountered during inductiolinical trials with

oxilorphan should be attempted with other addict populations to fully determine its potential therapeutic

value UI - 77115504

SO - Drug Alcohol Depend 1976;1:329-337

UI - 000226

AU - Tennant FS Jr.

AU - Detels R

AU - Clark V

TI - Some childhood antecedents of drug and alcohol abuse

AB - AB - Unsatisfactory intrafamilial relationships and child-rearing practices have frequently been

implicated as prime determinants of personalities that are susceptible to drug and alcohol abuse. Five

thousand forty-four US Army soldiers were surveyed by anonymous questionnaires. The reported

occurrence of a variety of activities, events and behaviors in childhood among drug and alcohol abusers were

compared to non users. Childhood antecedents that were associated with non-use of illegal drugs and which

showed as much as a 20% difference in reported occurrence between abusers and non-users of illegal drugs

were: spanking, church attendance, first alcoholic drink after 15 years, and perceived "happy" parental

marriage. These associations were found uithin white and non-white groups and in subjects with divorced or

separated parents. There was no antecedent that showed as much as a 20% difference in reported

occurrence between alcohol abusers and non-users UI - 76085301

SO - Am J Epidemiol 1975;102:377-385

UI - 000230

AU - Tennant FS Jr.

AU - Russell BA

AU - Casas SK

AU - Bleich RN

TI - Heroin detoxification. A comparison of propoxyphene and methadone

AB - AB - Propoxyphene napsylate and methadone hydrochloride were each administered under double-

blind conditions to 36 outpatients for 21- day heroin detoxification. The initial dosage was 24 mg/day for

methadone hydrochloride and 800 mg/day for propoxyphene napsylate. At these dosages, methadone more

effectively suppressed the opiate- withdrawal syndrome, and patients remained in treatment longer in the

methadone group (P greater than .05). In regard to heroin abstinence, however, results were not statistically

significant in either group, as indicated by the number of patients whose urine was positive for morphine on

admission and became negative during treatment, and the number who had morphine-negative urine at the

conclusion of 21-day treatment. A one-month follow-up of patients showed that more patients given

methadone had entered long-term medical maintenance while more patients given propoxyphene were

heroin-abstinent. This study indicates that 21-day heroin detoxification, regardless of chemotherapeutic

agent, yields a low rate of heroin abstinence UI - 75153849

SO - JAMA 1975;232:1019-1022

UI - 000223

AU - Halpern LM

TI - Treating pain with drugs

AB - AB - [No Abstract Available] UI - 74108808

SO - Minn Med 1974;57:176-184

UI - 000239

AU - Silsby H

AU - Tennant FS Jr.

TI - Short-term, ambulatory detoxification of opiate addicts using methadone

AB - AB - [No Abstract Available] UI - 75014945

SO - Int J Addict 1974;9:167-170

UI - 000220

AU - Halpern LM

TI - Analgesics and other drugs for relief of pain

AB - AB - [No Abstract Available] UI - 73169798

SO - Postgrad Med 1973;53:91-100

UI - 000258

AU - Marks RM

AU - Sachar EJ

TI - Undertreatment of Medical Inpatients with Narcotic Analgesics

AB - Structured interviews of 37 medical inpatients being treated with narcotic analgesics for pain showed

that 32% of the patients were continuing to experience severe distress, despite the analgesic regimen, and

another 41% were in moderate stress. Chart review suggested significant undertreatment with narcotics:

Meperidine in doses of 50 mg every 3-4 hours or less (if needed) was prescribed for 63% of the 37 patients;

a dose of 75 mg was prescribed for only 1 patient

SO - Ann Intern Med 1973;78:173-181

UI - 000231

AU - Tennant FS Jr.

TI - Drug abuse in the US Army, Europe

AB - AB - [No Abstract Available] UI - 73152205

SO - JAMA 1972;221:1146-1149

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