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
presented.
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
management
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
TI - OPIOID RESPONSIVENESS OF NEUROPATHIC CANCER PAIN: COMBINED ANALYSIS
OF SINGLE-DOSE ANALGESIC TRIALS (MEETING ABSTRACT)
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.
[Review]
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
comments]
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
programmable
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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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
children.
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
discussed.
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
pain
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
TI - EPIDURAL OPIATES AND LOCAL ANESTHETICS FOR THE MANAGEMENT OF
CANCER PAIN (MEETING ABSTRACT)
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
pain
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
practice
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
TI - THE INFLUENCE OF DRUG REGULATIONS ON OPIOID ANALGESIC PRESCRIBING
PRACTICE (MEETING ABSTRACT)
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
comments]
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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Date: Sat, 1 Jun 1996 17:18:59 +0000
Subject: Re: Pain Medication #1
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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
characteristics
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
application
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
3.4.24.11 in the brain and spinal cord of arthritic rats
AB - The possible changes in neutral endopeptidase EC 3.4.24.11 ("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
seen
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
patients
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
morphine
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:
21]
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
techniques
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
stimulation
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:
123]
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
cancer
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
arthritis
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
WORDS)
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
systems
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
chronic pain.(ABSTRACT TRUNCATED AT 400 WORDS)
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-
chymotrypsin
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
TI - NOVEL METHODS OF OPIOID ADMINISTRATION
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
patients
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>>
AB - AN: CHAPTER 86-246012-015<<SEE PREVIOUS CHAPTER>> <<SEE NEXT CHAPTER>> IN:
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
TRUNCATED AT 250 WORDS)
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
TI - INTRAVENOUS INFUSION OF OPIOIDS IN CANCER-RELATED PAIN: REVIEW OF CASES
AND GUIDELINES FOR USE
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
(LAAM)
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.
[German]
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
naloxone
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:
72-01628
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
tests
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
TRUNCATED AT 250 WORDS)
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:
71-26756
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
exchange
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.
[German]
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:
61-00418
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