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American Society for Action on Pain

Medical References on Pain and Pain Medication - Part 2

Author: Schnurr-R-F. MacDonald-M-R.

Title: Memory complaints in chronic pain.

Source: Clin-J-Pain. 1995 Jun. 11(2). P 103-11.



OBJECTIVE: In clinical practice, patients with chronic pain frequently report problems with memory functioning. This issue, however, has received little attention in the scientific literature. The present study was designed to investigate this common problem and to stimulate research interest in this neglected and important area.

DESIGN: Self-reported memory problems were investigated in two groups of chronic pain patients--patients with pain from acceleration-deceleration automobile accidents (n = 56) and patients with pain from various work accidents (n = 27)--and two control groups involving medical/dental (n = 24) and psychotherapy patients (n = 20). SETTING: Private practice, chronic pain, rehabilitation psychology services. RESULTS: Our findings suggest that memory complaints are higher in patients with chronic pain than in medical/dental or psychotherapy patients. No differences were found between chronic pain groups. On more general measures of memory complaint, differences between pain patients and controls were attributed to the severity of patients' depression. On a questionnaire designed to be more specific to memory complaint in chronic pain patients, differences in memory complaint between pain patients and controls were found, even after the effects due to depression were statistically removed. Although pain patients often attribute their memory problems to codeine use and/or psychoactive medications, there was no support for this in the present study.

CONCLUSIONS: Within the limitations of this study, these findings suggest that memory complaints may be related not only to depression but also to the presence of chronic pain. Further research in this area is needed.

Author: Enck-R-E.

Title: Pain management and parenteral opioids: an update.

Source: Am-J-Hosp-Palliat-Care. 1995 Sep-Oct. 12(5). P 8, 9-13.


Author: Junien-J-L. Riviere-P.

Title: Review article: the hypersensitive gut--peripheral kappa agonists as a new pharmacological approach.

Source: Aliment-Pharmacol-Ther. 1995 Apr. 9(2). P 117-26.


Abstract: Hypersensitivity to pain is a common component of functional bowel disorders. Hyperalgesia may be induced by various stimuli which produce a cocktail of inflammatory mediators that decrease the pain threshold. Drugs able to block these peripheral events within the gut may offer a new pharmacological approach for treating functional bowel disorders. Kappa opioids have been shown to inhibit somatic pain through a peripheral mechanism of action, acting directly on receptors located on peripheral sensory endings. They can block both the nociceptive messages as well as the release of sensory peptides. This paper reviews the effects of opioid agonists on gut visceral pain and motility anomalies induced by visceral pain. Kappa opioids have strong effects on all models tested, with a peripheral mechanism of action allowing the design of drugs acting only in the periphery and having no central nervous system side- effects. This contrasts with mu agonists which are centrally active on pain and worsen the subsequent transit and motility anomalies.

Author: Golinski-M-A. Fill-D-M.

Title: Preemptive analgesia.

Source: CRNA. 1995 Feb. 6(1). P 16-20.

Journal Title: CRNA.

Abstract: Preemptive analgesia describes a situation where the administration of a pharmacological agent administered before the onset of a painful stimulus causes a decrease in the intensity of pain felt, and subsequently there is a decrease in the total amount of analgesic required compared with the administration of an agent after a painful stimulus. It is best understood if it is thought of as a block to afferent impulses that are trying to reach the central nervous system before a tissue injury. Preemptive analgesia, administered in the form of narcotics, nonsteroidal antiinflammatory agents, or local anesthetics, is thought to alter peripheral and central sensitization to nociceptive impulses.

Author: Martin-M-I. Goicoechea-C. Ormazabal-M-J. Lopez-F. Alfaro-M- J.

Title: Analgesic effect of two calcitonins and in vitro interaction with opioids.

Source: Gen-Pharmacol. 1995 May. 26(3). P 641-7.


Abstract: 1. When the analgesic effect of salmon-calcitonin (S-CT) and of eel-calcitonin (E-CT), as well as their influence on the morphine-analgesia were compared, no significant differences were found. 2. While on isolated tissues, E-CT induced a significant increase on the effect of bremazocine, [D-Pen2,D- Pen5]enkephalin and [Met5]enkephalin and no changes were observed on the effect of DAMGO, suggesting that E-CT increases the effects of opioids acting on delta or kappa receptors but not on mu receptors. 3. These findings corroborate the possibility of interactions between calcitonin and the opioid system.

Author: Stein-C.

Title: The control of pain in peripheral tissue by opioids.

Source: N-Engl-J-Med. 1995 Jun 22. 332(25). P 1685-90.


Author: Scholz-M-J.

Title: Assessing safety of opioids for chronic pain.

Source: RN. 1995 Apr. 58(4). P 71.

Journal Title: RN.

Author: Antonijevic-I. Mousa-S-A. Schafer-M. Stein-C.

Title: Perineurial defect and peripheral opioid analgesia in inflammation.

Source: J-Neurosci. 1995 Jan. 15(1 Pt 1). P 165-72.


Abstract: Opioid receptors have been demonstrated on sensory nerves in both inflamed and normal subcutaneous tissue but locally applied opioid agonists produce analgesia in inflamed tissue only. Inflammation confers a disruption of the perineurial barrier that can also be induced deliberately by hyperosmolar solutions. The present study examines at which stage of Freund's adjuvant-induced inflammation peripheral opioid analgesic effects become manifest and whether a perineurial defect contributes to the appearance of such effects. To this end we have monitored the temporal evolution of inflammatory signs (swelling, temperature, hyperalgesia) and of peripheral antinociceptive effects (by the paw pressure test) of mu-, delta-, and kappa-selective opioids. Using horseradish peroxidase histochemistry, the perineurial barrier was assessed in normal and inflamed tissue and following its artificial disruption by hyperosmolar saline and mannitol in vivo. Finally, we sought to elicit analgesia in normal tissue by the concomitant application of mannitol and receptor-selective opioids or by an extremely lipophilic opioid agonist (fentanyl). We found that peripheral opioid antinociception and perineurial leakage occur simultaneously at a very early stage (within 12 hr) of the inflammatory reaction and that both can be mimicked by the administration of hyperosmolar solutions in normal tissue. Fentanyl produced peripheral antinociception in noninflamed tissue that was potentiated by mannitol or inflammation. Our findings demonstrate that the perineurium is a crucial determinant for peripheral opioid analgesia and that the efficacy of locally applied hydrophilic or lipophilic neuromodulatory compounds can be improved dramatically by the concomitant modulation of perineurial permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Author: Fowler-C-J. Fraser-G-L.

Title: Mu-, delta-, kappa-opioid receptors and their subtypes. A critical review with emphasis on radioligand binding experiments [see comments]

Source: Neurochem-Int. 1994 May. 24(5). P 401-26.

Comment: Comment in: Neurochem-Int. 1994 May. 24(5). P 433-7.


Abstract: Since the early 1970's, when specific binding sites for opiates were first described, there has been a vast literature on opiate receptors, their subtypes, and even the multiplicity of these subtypes. In the present review, the signal transduction pathways, structure, and brain and spinal cord localization of the established subtypes (mu, delta, kappa) are reviewed. In addition, evidence suggesting heterogeneity of these subtypes, in particular from radioligand binding studies, is discussed critically.

Author: Ziegler-D-K.

Title: Opiate and opioid use in patients with refractory headache [see comments]

Source: Cephalalgia. 1994 Feb. 14(1). P 5-10.

Comment: Comment in: Cephalalgia. 1994 Dec. 14(6). P 466-7.

Journal Title: CEPHALALGIA.

Abstract: Opiate and opioid analgesics are commonly used for pain in general and presumably for headache. Codeine, oxycodone and propoxyphene, among the most commonly prescribed, do carry some risk of abuse, and their efficacy in headache patients has not been well studied. In many patients with other kinds of pain, however, both of neoplastic and non-neoplastic origin, chronic opiate use has been demonstrated to be of benefit without adverse side effects. The type of headache patient with intractable pain who needs frequent opiate analgesic and who does not develop addiction or drug abuse is an important subject for research.

Author: Joranson-D-E. Gilson-A-M.

Title: Policy issues and imperatives in the use of opioids to treat pain in substance abusers.

Source: J-Law-Med-Ethics. 1994 Fall. 22(3). P 215-23.


Author: Sjogren-P. Jensen-N-H. Jensen-T-S.

Title: Disappearance of morphine-induced hyperalgesia after discontinuing or substituting morphine with other opioid agonists.

Source: Pain. 1994 Nov. 59(2). P 313-6.

Journal Title: PAIN.

Abstract: Hyperalgesia and allodynia in 4 cancer patients treated with morphine disappeared after discontinuing or substituting morphine with other opioid agonists. The first case describes a young female who developed hyperalgesia and myoclonus during intravenous morphine infusion. The hyperalgesia and myoclonus disappeared when the morphine administration was discontinued and she felt comfortable on small and sporadic oral doses of methadone. The second case describes hyperalgesia occurring after a small dose of sustained-release morphine which disappeared after alternative use of oral ketobemidone. The third case describes hyperalgesia following high doses of intramuscular morphine which disappeared after alternative use of continuous subcutaneous infusion of sufentanil. The fourth case describes a boy developing hyperalgesia after high doses of oral and intramuscular morphine. The hyperalgesia disappeared after discontinuing morphine administration but withdrawal symptoms developed due to too small doses of methadone. Possible mechanisms of morphine-induced hyperalgesia are discussed.

Author: Turk-D-C. Brody-M-C. Okifuji-E-A.

Title: Physicians' attitudes and practices regarding the long-term prescribing of opioids for non-cancer pain.

Source: Pain. 1994 Nov. 59(2). P 201-8.

Journal Title: PAIN.

Abstract: Prescribing long-term opioids for patients with chronic pain is controversial. The primary purpose of this study was to examine physicians' beliefs about and prescribing of the long-term use of opioids in the treatment of chronic pain patients. Concerns about regulatory pressure and appropriateness of education regarding opioids were also examined. The design was a stratified random sample. In the United States, 6962 physicians were randomly selected from two states in each of five regions of the country (Northeast, Midwest, Southeast, Southwest, and Pacific). Physicians from seven medical specialties (Family Practice, Internal Medicine, Physical Medicine and Rehabilitation, Rheumatology, Orthopedic Surgery, Neurosurgery, and Neurology) were surveyed and 1912 (27.46%) responded. A survey consisting of questions regarding years of practice, number of chronic pain patients treated, frequency of prescribing long-term opioids, concerns about opioids, goals of treatment, beliefs about education regarding opioids, and concerns about regulatory pressures was used. Based on the physicians who responded, it appears that prescription of long-term opioids is relatively wide-spread. Differences were noted by region, specialty, and the requirement for the use of multiple prescriptions for schedule II drugs. Physicians in the Midwestern United States were the least likely to prescribe the long-term use of opioids. Rheumatologists and general practitioners were significantly more likely to prescribe long-term opioids than were surgeons, neurologists, or physiatrists and were more likely to emphasize the importance of symptom improvement as an appropriate goal even in the absence of functional improvements.(ABSTRACT TRUNCATED AT 250 WORDS)

Author: Cherry-D-A. Gourlay-G-K.

Title: Pharmacological management of chronic pain: a clinician's perspective.

Source: Agents-Actions. 1994 Oct. 42(3-4). P 173-4.


Abstract: Of the currently available mu agonist drugs, the following are relatively contraindicated: 1. Methadone--unpredictable duration of action [5]. 2. Pethidine--unwanted central effects, metabolised to an active metabolite and too short acting. 3. Codeine--too weak and with constipating side-effects. 4. Fentanyl--too short acting. 5. Oxycodone--too short acting although suppositories may overcome some theoretical disadvantages. 6. Dextropropoxyphene--weak agonist which is possibly metabolised to a cardiotoxic metabolite [6]. Morphine remains the drug of choice for chronic pain when administered in a sustained release preparation. MS Contin, a slow release oral formulation of morphine, is available and has a predictable duration of action lasting from 8-12 h, while improved formulations are about to be released in the near future in some countries. Prescribers need to take into account the relatively poor oral bioavailability of morphine when calculating the daily morphine dose.

Author: Pribilla-O.

Title: Medical legal and ethical questions in palliative medicine and euthanasia.

Source: Forensic-Sci-Int. 1994 Dec 16. 69(3). P 299-306.


Abstract: The increasing importance of legal and ethical questions in palliative medicine and euthanasia due to the increased technical possibilities for extending life will be considered. In palliative medicine, the choice of the best therapy will be discussed, especially in the case of oncological diseases. Here, consideration of the prospects of success, for example, in chemotherapy, is faced with partly serious side-effects. The requirements of palliative medicine that the patient has to be fully informed of the fatal prognosis of his disease is equally debated as the optimum pain therapy. In this respect, the modification of the Narcotics Act of 1 February 1993 is also under discussion. In the field of euthanasia, the technical development of life extension versus dying has raised considerable legal and ethical problems regarding termination of therapy. Additionally, fiscal considerations are of increasing relevance. The common development of the legal and ethical discussion, for example, with regard to the publicity of the work of the so-called 'Gesellschaft fur humanes Sterben', the public discussion leading up to a hearing of the 'Bundestag' regarding active euthanasia leads to a realization of the subject. The proposals for an active termination of life by discontinuing therapy for adults and also for malformed newborns are discussed. A dispute concerning the new legal regulation of active euthanasia in the Netherlands of February 1993 is also discussed. There, around 2% of all deaths per year result from active termination of life and also cases where persons are not able to consent. This also has enormous consequences for the position of the physician.(ABSTRACT TRUNCATED AT 250 WORDS)

Author: Platt-D.

Title: Important principles of effective pain management.

Source: Conn-Med. 1994 Nov. 58(11). P 667-9.


Author: Goodman-N-W.

Title: Recent advances in pain relief [letter; comment] [published erratum appears in Br J Hosp Med 1994 May 4- 17;51(9):496]

Source: Br-J-Hosp-Med. 1994 Apr 20-May 3. 51(8). P 433.

Comment: Comment on: Br-J-Hosp-Med. 1993 Nov 17-Dec 14. 50(10). P 616-8.


Author: Rabenstein-K.

Title: Recent advances in pain relief [letter; comment]

Source: Br-J-Hosp-Med. 1994 Apr 20-May 3. 51(8). P 431.

Comment: Comment on: Br-J-Hosp-Med. 1993 Nov 17-Dec 14. 50(10). P 616-8.


Author: Oh-V-M.

Title: The placebo effect: can we use it better? [editorial] [see comments]

Source: BMJ. 1994 Jul 9. 309(6947). P 69-70.

Comment: Comment in: BMJ. 1994 Sep 10. 309(6955). P 667.

Journal Title: BMJ.

Author: Lindley-C.

Title: Overview of current development in patient-controlled analgesia.

Source: Support-Care-Cancer. 1994 Sep. 2(5). P 319-26.


Abstract: Over the past two decades, numerous trials have assessed the safety and efficacy of patient-controlled analgesia (PCA). Advantages over conventional parenteral narcotics reported from these trials include equivalent to superior pain relief, superior patient satisfaction, decreased sedation and anxiety, faster return to normal functional status, and reduction in nursing time and hospitalization. The majority of these trials have been conducted in the postoperative patient population. In the mid to late 1980s, interest arose in applying PCA technology to the management of cancer pain. Factors that served as an impetus for the use of PCA in cancer pain included favorable reports from the postoperative setting and the often-cited statistics regarding the magnitude of the cancer pain problem. Advances in PCA technology coupled with advances in vascular access technology that allow the placement of long-term ports and catheters to facilitate intravenous, epidural, or intrathecal administration of opioid analgesics have made the applicability of PCA in ambulatory cancer patients an attractive option. The greatest breakthrough in PCA technology came with the introduction of devices making it possible to choose between intermittent (demand bolus) and continuous administration (continuous infusion) or both intermittent and continuous modes. A comparison of these types of PCA devices is described. The limitations of the literature involving PCA therapy in cancer patients make it difficult to identify optimal patient selection criteria, PCA administration schedules, drug selection and dosing, and optimal route of administration. The current status and pertinent issues related to these topics are addressed.

Author: McCaffery-M. Ferrell-B-R.

Title: Nurses' assessment of pain intensity and choice of analgesic dose.

Source: Contemp-Nurse. 1994 Jun. 3(2). P 68-74.


Abstract: Under-treatment of all types of pain has been identified in many countries throughout the world. For example, the World Health Organization states that unrelieved cancer pain is an international problem. Lack of education of health care professionals, including nurses, is frequently cited as a major reason for under-treatment of pain. This survey of 517 Australian nurses suggests that they have some of the same educational needs as nurses in North America, such as how to assess pain intensity and how to select a dose of an opioid analgesic that is appropriate for the individual patient.

Author: Chapman-V. Haley-J-E. Dickenson-A-H.

Title: Electrophysiologic analysis of preemptive effects of spinal opioids on N-methyl-D-aspartate receptor-mediated events.

Source: Anesthesiology. 1994 Dec. 81(6). P 1429-35.


Abstract: BACKGROUND: Spinal N-methyl-D-aspartate (NMDA) receptor- mediated mechanisms may contribute to reduced opioid sensitivity in conditions of pain. The effectiveness of spinal opioids in inhibiting NMDA-mediated nociceptive events was assessed with two models. In addition, opioid dose-response curves with preemptive administration were compared with early and late postadministrations. METHODS: Dorsal horn nociceptive neuronal responses were recorded in the intact halothane anesthetized rat to acute repetitive C-fiber electrical stimulation (0.1 and 0.5 Hz) and to the peripheral injection of 5% formalin. At 0.5 Hz but not at 0.1 Hz, there was an enhanced C-fiber evoked response of dorsal horn neurons elicited by repetitive C-fiber stimulation (wind-up), which is mediated by the NMDA receptor. Formalin produced a biphasic response; the late protracted inflammatory phase was NMDA receptor-mediated. RESULTS: With 0.5-Hz stimulation a large degree of wind-up was elicited; it was less sensitive to 5 micrograms morphine compared with the effect of the same dose on the residual wind- up elicited at 0.1 Hz. Preadministration and early postadministration of morphine were equieffective at inhibiting the second-phase formalin response. In contrast, administration of the fast-acting mu opioid, D-Ala-Gly-MePHe-Gly-ol, given late postadministration (during the second phase) was less effective than preadministration. Increasing the dose of D-Ala- Gly-MePHe-Gly-ol produced complete inhibitions.

CONCLUSIONS: NMDA receptor-mediated neuronal responses, such as wind-up and the established second phase of the formalin response, are poorly responsive to opioids. Dose increases and preemptive opioids effectively inhibit these NMDA receptor-mediated events.

Author: Santill'an-R. Maestre-J-M. Hurl'e-M-A. Fl'orez-J.

Title: Enhancement of opiate analgesia by nimodipine in cancer patients chronically treated with morphine: a preliminary report.

Source: Pain. 1994 Jul. 58(1). P 129-32.

Journal Title: PAIN.

Abstract: The ability of nimodipine, a calcium-channel blocker, to enhance morphine analgesia and/or modify the development of tolerance was studied in patients with cancer pain who had needed successive increments of morphine for periods ranging from 21 to 780 days. Assessment of daily morphine consumption was the primary effect parameter. Nimodipine succeeded in reducing the daily dose of morphine in 16 of 23 patients (oral, n = 13; intrathecal, n = 3), and failed to modify it in 2 patients. Total oral daily dose was reduced by nimodipine (120 mg/day) from 282.6 +/- 47.7 mg to 158.7 +/- 26.2 mg (n = 15, P < 0.001). Intrathecal morphine was also reduced by 1-5 mg/day. Nimodipine was withdrawn in 5 patients during the first week of treatment due to intolerance (n = 3) or aggravation of the disease (n = 2). These preliminary results support experimental findings showing that pharmacological interference with Ca(2+)-related events may modify chronic opioid effects, including the expression of tolerance.

Author: Elizaga-A-M. Smith-D-G. Sharar-S-R. Edwards-W-T. Hansen-S-T- Jr.

Title: Continuous regional analgesia by intraneural block: effect on postoperative opioid requirements and phantom limb pain following amputation.

Source: J-Rehabil-Res-Dev. 1994 Aug. 31(3). P 179-87.


Abstract: The objective of this study was to assess the effectiveness of a previously described technique of regional analgesia (continuous infusion of local anesthetic through a catheter placed at the time of amputation within the exposed sciatic or posterior tibial nerve) on relieving the postoperative pain in a heterogeneous group of patients who underwent lower extremity amputations. A second objective was to determine the effect of such treatment on the incidence and characteristics of phantom limb pain 6 months or more after surgery in the same patients. The study design was retrospective, unblinded, controlled (postoperative pain), and unblinded questionnaire and interview (phantom pain) were utilized. Subjects were inpatients at Harborview Medical Center, University of Washington, Seattle, WA. Nineteen bupivacaine-treated and 40 nonbupivacaine-treated patients who underwent lower extremity amputation subsequent to trauma, infection, long-standing injury (poor or no function), congenital deformity, or burns were evaluated in the postoperative pain management assessment. Nine treated and 12 untreated patients were interviewed in the phantom pain assessment. Bupivacaine 0.5% 2-6 ml/h was infused through a polyamide 20-gauge catheter inserted into the sciatic or posterior tibial nerve sheath under direct vision at the time of surgery. All patients, treated and control, received opioid analgesics systemically during the 72-hour period of study. The postoperative opioid analgesic requirement of treated patients was compared with that of control patients who received opioid analgesics alone. A questionnaire was administered to assess presence, severity, and character of phantom pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Author: Bilfinger-T-V. Kushnerik-V.

Title: The use of morphine in surgery: an overview.

Source: Adv-Neuroimmunol. 1994. 4(2). P 133-44.


Author: Krick-S-E. Lindley-C-M. Bennett-M.

Title: Pharmacy-perceived barriers to cancer pain control: results of the North Carolina Cancer Pain Initiative Pharmacist Survey.

Source: Ann-Pharmacother. 1994 Jul-Aug. 28(7-8). P 857-62.


Abstract: OBJECTIVE: To assess pharmacists' knowledge, attitudes, and beliefs regarding the use of narcotics in cancer pain management, identify pharmacist counseling activities for cancer pain patients, assess pharmacy- related barriers to cancer pain management, and evaluate the availability of narcotic analgesics. METHODS: Mailing of a six-page survey. SETTING: Five hundred randomly selected pharmacists registered in North Carolina. PARTICIPANTS: Of 500 pharmacists surveyed, 141 surveys were completed and returned for a response rate of 28.2 percent. RESULTS: Pharmacists surveyed were knowledgeable regarding the problem of undertreatment of cancer pain. More than 80 percent of respondents replied that most cancer patients experience pain at some time during their illness. Eighty-five percent of respondents agreed that the nurse must believe the patient's report of pain and that the patient is the best judge of the intensity of the pain. Conservative physician prescribing patterns and conservative administration patterns of nurses were identified as perceived barriers to adequate pain management by 51 and 44 percent of respondents, respectively. Less than 30 percent of respondents frequently counseled cancer pain patients and were unable to identify patients who have cancer pain as a major medical illness. Hospital pharmacists recommended adjunctive therapy more often than did community pharmacists (p = 0.013). Interventions in pain management regimens were more often conducted by hospital pharmacists than by community pharmacists (p = 0.049). Differences in availability of narcotics was noted among practice sites for some more potent narcotics. Of the pharmacists surveyed, only 43 percent had attended a continuing education program on cancer pain management. Ninety-six percent of respondents were interested in attending a continuing education program in the future.

CONCLUSIONS: Pharmacists in North Carolina are aware that the undertreatment of cancer pain is a serious medical problem. Unfortunately, pharmacists appear to be unable to identify patients with cancer pain as a major medical problem; therefore, counseling activity is limited. Addiction is still perceived as a barrier by some pharmacists. Through organizations such as the North Carolina Pain Initiative, these problems can be addressed.

Author: Jamison-R-N. Anderson-K-O. Peeters-Asdourian-C. Ferrante-F-M.

Title: Survey of opioid use in chronic nonmalignant pain patients.

Source: Reg-Anesth. 1994 Jul-Aug. 19(4). P 225-30.


Abstract: BACKGROUND AND OBJECTIVES. Opioids have been accepted as appropriate treatment for acute and cancer pain, but remain controversial for use with chronic nonmalignant pain. Clinicians are concerned about efficacy, tolerance, addiction, and unwanted side effects. METHODS. The aim of this study was to survey chronic pain patients who were taking opioids for their pain, to determine the incidence of these adverse conditions. Two hundred seventeen patients who were being treated for their pain at two different pain centers completed a medication questionnaire. The most common diagnosis was low back pain. One hundred twelve patients reported taking oral opioids for their pain. RESULTS. Of the patients who reported taking opioids for their chronic pain, 83% felt that the opioids were moderately beneficial in relieving their pain; 25% felt that the opioid had not lost its ability to relieve the pain over time; 35% reported that they did not need to increase their medication; 36% expressed no fear of addiction or dependence; and 56% reported having no unwanted side effects.

CONCLUSIONS. The results suggest that chronic nonmalignant pain patients taking opioids for their pain reported some tolerance, fear of addiction, and side effects when taking opioids. However, despite these concerns, some of these patients felt that opioid therapy was very beneficial. Further investigations are needed to determine which patient characteristics predict benefit from opioid therapy for nonmalignant pain.

Author: King-J-C. Kelleher-W-J. Stedwill-J-E. Talcott-G.

Title: Physical limitations are not required for chronic pain rehabilitation success.

Source: Am-J-Phys-Med-Rehabil. 1994 Sep-Oct. 73(5). P 331-7.


Abstract: A high performance, active duty fitness requirement group rehabilitated equally to a low performance needs civilian group, both suffering from disabling chronic pain. The purpose of this prospective study was to determine whether higher physical performance requirements adversely affected outcome in a chronic pain rehabilitation program. Twenty-three active duty, chronic pain patients were treated along with 22 civilian chronic pain sufferers in a behavior modification, including positive, verbal reinforcement for performance, stress management and family counseling, physical reconditioning, including stretching, strengthening and aerobic conditioning in a slowly progressive fashion to required needs, and narcotic and muscle relaxant detoxification program at a major military medical center. Eighteen patients in each group, representing, respectively, 78 and 82% of the military and civilian participants, successfully completed the inpatient program. Success was defined by (1) elimination of all narcotics and minor tranquilizers, (2) elimination of all physical restrictions that precluded any desired work or play, which required much higher levels for the active duty patients that included: (3) elimination of all physical profile restrictions and (4) objectively passing annual aerobics field test requirements before the program's end. Review of military disability separation records, averaging 24 mo posttreatment, showed that no formerly successful active duty patients had later been discharged because of physical impairments. Of individuals responding to mail questionnaires at an average of 19 mo postprogram, 12 of 14 (86%) initially successful military patients reported continued unrestricted maintenance of physical abilities, whereas 10 of 14 (71%) of the initially successful civilians reported no restrictions in desired activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Author: Meert-T-F. De-Kock-M.

Title: Potentiation of the analgesic properties of fentanyl-like opioids with alpha 2-adrenoceptor agonists in rats.

Source: Anesthesiology. 1994 Sep. 81(3). P 677-88.


Abstract: BACKGROUND: Data on the analgesic properties of alpha 2 agonists and their interactions with opioids are conflicting. Experiments were conducted in rats to evaluate whether various available alpha 2 agonists can potentiate the analgesic properties of opioids and to determine the route of administration needed for optimal interaction. METHODS: The tail-withdrawal reaction test was used as an analgesia assay. In separate experiments, the interactions between systemic (subcutaneous, intravenous, and intraperitoneal) and spinally (epidural and intrathecal) administered alpha 2 agonists and opioids were evaluated. The antagonism of medetomidine plus fentanyl with naloxone and/or idazoxan also was studied. RESULTS: All alpha 2 agonists tested, when injected subcutaneously with fentanyl, potentiated the opioid-induced analgesia. In terms of a reduction of the amount of fentanyl needed to produce a deep surgical analgesia (tail-withdrawal reaction latency > or = 10 s) over more than 2 h, the relative order of potency of the alpha 2 agonists tested was: medetomidine > dexmedetomidine > xylazine > clonidine > detomidine. For some of these alpha 2 agonists there was a biphasic effect: at the larger doses tested, a reduction in the fentanyl potentiation was present. The potentiation of the opioid activity with alpha 2 agonists was also demonstrated in terms of a longer duration of analgesia after combined treatment with fixed doses of opioids. The interaction between the alpha 2 agonists and the opioids remained present when a more profound criterion of analgesia (tail-withdrawal reaction latency > or = 30 s) was used. Furthermore, the interactions between the alpha 2 agonists tested and fentanyl or sufentanil appeared to be independent of the route of administration. Potentiations were observed after simultaneous subcutaneous injections of both groups of compounds, after the combination of intraperitoneal (alpha 2 agonist) plus subcutaneous (opioid), intravenous (alpha 2 agonist) plus epidural (opioid) and simultaneous epidural or intrathecal administrations. With regard to antagonism of the analgesic activity of combined treatment with alpha 2 agonists plus opioids, naloxone provided total antagonism, whereas the alpha 2 antagonist idazoxan overcame only the alpha 2 agonist-induced potentiation of fentanyl.

CONCLUSIONS: The tested alpha 2 agonists can potentiate the analgesic properties of opioids, but they have no intrinsic antinociceptive effects on spinal reflexes on their own. The potentiating activities of the alpha 2 agonists could be measured both in terms of a reduction of the amount of opioid needed to reach a particular level of analgesia and in terms of a longer duration of analgesia with a fixed dose of the opioid. The potentiations were observed with various alpha 2 agonists and opioids and appeared independent of the routes of administration.

Author: Poyhia-R.

Title: Opioids in anaesthesia: a questionnaire survey in Finland.

Source: Eur-J-Anaesthesiol. 1994 May. 11(3). P 221-30.


Abstract: A questionnaire was sent to the pharmacies of 88 Finish hospitals with surgical departments to inquire about the consumption of opioids during 1990. Another questionnaire was sent to 480 members of the Finnish Society of Anaesthesiologists to ask how they administer opioids to adult patients. Answers were received from 95% of hospitals and 67% of anaesthetists. Dextropropoxyphene was the most common oral opioid and oxycodone was the most common parenteral opioid used in Finland. Parenteral opioids were consumed almost totally in the hospitals. The anaesthetists reported oxycodone to be the opioid of choice for premedication, postoperative pain and sedation of critically ill patients. Fentanyl was the opioid most commonly used intravenously during balanced anaesthesia and in epidural administration. Epidural opioids were administered by 77% of anaesthetists and patient- controlled analgesia (PCA) technique mostly for intravenous administration by 19%. Only 10% of Finnish anaesthetists were actively involved in the management of chronic pain; the methods they use are discussed. The majority of anaesthetists were satisfied with the currently available opioids.

Author: Richardson-M.

Title: Conquering cancer pain. New guidelines try to overcome old myths about the use of narcotics.

Source: Tex-Med. 1994 May. 90(5). P 28-31.

Journal Title: TEXAS MEDICINE.

Author: Eriksen-J. Clausen-T-G. Borgbjerg-F-M.

Title: [Opioid analgesics in the treatment of non-malignant chronic pain]

Source: Ugeskr-Laeger. 1994 Jan 31. 156(5). P 621-3, 626-7.


Abstract: Opioid sensitivity, residual pain, development of tolerance, physical and psychological dependence are described and discussed in relation to long-term opioid therapy. Based on this, guidelines for long-term opioid administration are established for chronic pain conditions of non-cancer origin. The indication must be well-considered--a life-long treatment may be instituted. Prior to final initiation of the treatment, a testing of the selected drug and method of administration should be performed. Due to the compliance- reasons, only long acting opioids should be used (controlled release morphine preparations, methadone, buprenorphine) and the route of administration should always be oral. The treatment must be individualised, covering 24 hours a day. The single dosages should be identical and administered with identical time intervals, which are determined by the duration of action of the drug in use. P.r.n.-administration should not be allowed. Only one physician should be responsible for the treatment and for the prescription of the opioid analgesic drugs.

Author: Lewis-K-S. Whipple-J-K. Michael-K-A. Quebbeman-E-J.

Title: Effect of analgesic treatment on the physiological consequences of acute pain.

Source: Am-J-Hosp-Pharm. 1994 Jun 15. 51(12). P 1539-54.


Abstract: Physiological responses to acute pain are described, and the effects of different analgesic techniques on these responses are discussed. The body's response to acute pain can cause adverse physiological effects. Pain can impede the return of normal pulmonary function, modify certain aspects of the stress response to injury, and alter hemodynamic values and cardiovascular function. It can produce immobility and contribute to thromboembolic complications. In addition, pain can slow a patient's recovery from surgery and contribute to increased morbidity. Fewer pulmonary complications occur when adequate analgesia is provided through the use of epidural narcotics and local anesthetics, particularly if the injury or surgery involves the lower part of the body. Continuous morphine infusions, intercostal nerve blocks, and transcutaneous electrical stimulation do not alter the frequency of pulmonary complications. The effectiveness of patient-controlled analgesia in reducing postoperative pulmonary complications is still not known. Epidural local anesthetic therapy inhibits the stress response, particularly in operations involving the lower abdomen or extremities; this technique is less effective during major abdominal procedures. Suppression of endocrine-metabolic changes following lower abdominal surgery requires neural block to the fourth thoracic segment. Epidural narcotics partially inhibit the stress response after lower abdominal or extremity surgery but not after upper abdominal or thoracic surgery. Local anesthetics applied to the surgical site, intercostal nerve blocks, and intrapleural and intraperitoneal administration also do not modify the stress response. Adequate analgesia through the use of local anesthetics and narcotics postoperatively generally results in improved cardiovascular function, decreased pulmonary morbidity and mortality, earlier ambulation, and decreased likelihood of deep vein thrombosis. Some data suggest that improved patient outcome occurs with adequate analgesia. Block of afferent and efferent neural pathways by local anesthetics seems to be the most effective analgesic modality in lessening the physiologic response to pain and injury.

Author: Li-Q-S. Cao-S-H. Xie-G-M. Gan-Y-H. Ma-H-J. Lu-J-Z. Zhang- Z-H.

Title: Combined traditional Chinese medicine and Western medicine. Relieving effects of Chinese herbs, ear-acupuncture and epidural morphine on postoperative pain in liver cancer.

Source: Chin-Med-J-Engl. 1994 Apr. 107(4). P 289-94.


Abstract: In the evaluation of Chinese herbs (A), ear-acupuncture (B) and epidural morphine (C) to relieve postoperative pain and abdominal distension, sixteen male patients with primary liver cancer were observed. This study was conducted by means of orthogonal experiment and double blind, randomized design. The patients received various treatments according to the display of the orthogonal table L16(2)15 which corresponds to 2(3) factorial experiment design. C+ (morphine 2 mg) was given before the peritoneum was sutured. A+ (orally administered) and B+ were given 24 hours after operation. 50-100 mg of pethidine was given when the pain intensity VAS (0-100) exceeded 50-70. The observation parameters included plasma leucine enkephalin (LEK), postoperative total dosage of narcotics administered for 5 days, VAS for pain and pain reliever, abdominal distension, urinary retention, constipation, etc. The results were as follows: a. Patients who had received A (A+B+C+, A+B+C-, A+B-C-, A+B-C+); C (C+A+B+, C+A+B-, C+A-B+, C+A-B-), or B (B+A+C+, B+A+C-, B+A-C+, B+A-C-) produced better analgesic effects than those who had received placebo. The A, B, and C reduced narcotics 650, 450 and 550 mg respectively when compared with placebo. The effects of A and C were of statistical significance (P < 0.05), while AB, BC, and AC interactions were not found; b. A and B minimized abdominal distension and urinary retention, while C prolonged them. As compared with the placebo, A and B accelerated restoration of bowel peristalsis (P < 0.05, ANOVA). Both A and B decreased it for 165 hours, while epidural morphine prolonged it for 49 hours; and c.(ABSTRACT TRUNCATED AT 250 WORDS)

Author: Portenoy-R-K.

Title: Management of common opioid side effects during long-term therapy of cancer pain.

Source: Ann-Acad-Med-Singapore. 1994 Mar. 23(2). P 160-70.


Abstract: For most patients with cancer pain, the primary goal of opioid pharmacotherapy is a satisfactory balance between analgesia and side effects. Consequently, the assessment and treatment of opioid side effects is a fundamental aspect of therapy, which may increase the likelihood of a favourable treatment outcome, potentially allow higher and more efficacious opioid doses, and improve quality of life by reducing other uncomfortable symptoms. This review describes the presentation, assessment and management of adverse neuropsychological and gastrointestinal effects due to opioid drugs. These common side effects pose the major challenge for the clinician who undertakes the long-term opioid therapy of patients with cancer pain.

Author: Hecker-R-B.

Title: Spinal narcotics for chronic noncancer pain warrants further investigation [editorial]

Source: J-Am-Osteopath-Assoc. 1994 Jun. 94(6). P 477-8.


Author: Rapp-S-E. Wild-L-M. Egan-K-J. Ready-L-B.

Title: Acute pain management of the chronic pain patient on opiates: a survey of caregivers at University of Washington Medical Center.

Source: Clin-J-Pain. 1994 Jun. 10(2). P 133-8.


Abstract: OBJECTIVE: The provision of acute pain management for the chronic pain patient can pose a challenge. We sought to characterize management issues. SUBJECTS/SETTING: An anonymous survey was distributed to 270 physicians and 212 nurses at University of Washington Medical Center (UWMC) in an attempt to characterize management issues. DESIGN: Caregivers were queried regarding treatment modalities, efficacy of anxiolysis, patient attributes, concern of the quantity of medication, criteria for patient evaluation, and other management issues. RESULTS: Of the respondents, 61.8% were physicians, and 38.2% were nurses. The mean duration in practice was 7.7 years. The responses from the two groups were similar. Seventy-five percent reported using different pain-evaluation techniques for chronic pain patients than those utilized for the "average" patient. Pain scores were used frequently in the average patient, whereas ability to perform activities was used more commonly in the chronic pain patient (p < 0.0001). Half of the respondents expressed concern regarding the amount of medication used and level of sedation. The same proportion found anxiolysis to be a helpful adjunct. The use of a time- contingent "pain cocktail" as an oral medication was a useful strategy for 88% of respondents. The least labor- intensive modality reported was patient-controlled analgesia (PCA) for 84.5% of respondents; intravenous opiate fusion, 5.3%; and epidural analgesia, 11.2%.

CONCLUSIONS: The survey describes caregiver concerns regarding this patient population, including medication use, sedation, length of hospital stay, and evaluation techniques.

Author: Kenner-D-J.

Title: Pain forum. Part 2. Neuropathic pain.

Source: Aust-Fam-Physician. 1994 Jul. 23(7). P 1279-83.


Abstract: Neuropathic pain is often a reason for an unfavourable response to morphine or other opioids in treating cancer pain. This type of pain is difficult to manage and may co-exist with nociceptive cancer pain. There is still a potential for opioid responsiveness, although the doses needed will be higher, and adjuvant drug therapies are best employed concurrently with opioid drugs. Adjuvant drugs used are the antidepressants, anticonvulsants, including benzodiazepines, corticosteroids and neurolepts. Less commonly, agents such as baclofen and clonidine, and sympatholytic drugs such as prazosin can be employed for sympathetically maintained neuropathic pain (discussed in Part 3). The type of agent selected will depend on the natural history of the disease process, as well as a description of the pain-- the lancinating pains tending to respond better to anticonvulsants. Non invasive neurostimulatory approaches such as transcutaneous electrical nerve stimulation (TENS) may be useful in management, and a few patients may require an invasive procedure such as dorsal column stimulation.

Author: Canty-S-L.

Title: Constipation as a side effect of opioids.

Source: Oncol-Nurs-Forum. 1994 May. 21(4). P 739-45.


Abstract: PURPOSE/OBJECTIVES: To describe the phenomenon of opioid- induced constipation and its treatment. DATA SOURCES: Published books and journal articles; commercial pharmacologic information. DATA SYNTHESIS: Patients receiving opioid analgesia are at risk for constipation and its complications. A number of pharmacologic and nonpharmacologic interventions are available to prevent and treat this problem.

CONCLUSIONS: Discomfort from this opioid side effect can be particularly distressing to patients with cancer who already suffer from pain. Accurate assessment and individualized interventions are needed. IMPLICATIONS FOR NURSING PRACTICE: Collaboration with physicians to determine appropriate drug or nondrug interventions and patient and family education regarding the problem, preventive action, and appropriate treatment methods.

Author: Hill-T-P.

Title: Freedom from pain: a matter of rights?

Source: Cancer-Invest. 1994. 12(4). P 438-43.


Author: Scott-J-L. Smith-M-S. Sanford-S-M. Shesser-R-F. Rosenthal-R- E. Smith-J-P. Feied-C-F. Ghezzi-K-T. Hunt-D-M.

Title: Effectiveness of transnasal butorphanol for the treatment of musculoskeletal pain.

Source: Am-J-Emerg-Med. 1994 Jul. 12(4). P 469-71.


Abstract: A prospective, open-label study of the effectiveness of transnasal butorphanol in the treatment of pain resulting from musculoskeletal injuries. Twenty-eight patients with strains (n = 20), fractures (n = 6), contusions (n = 1), and stab wounds (n = 1) were included. All patients were examined by an attending level emergency medicine physician and deemed to have pain severe enough to warrant parenteral narcotic analgesia. All patients received an initial 1-mg dose of transnasal butorphanol. Subsequent dosing was flexible depending on response to the initial dose. All patients received pain relief from transnasal butorphanol, and only one requested alternative analgesic medication. Fifty- seven percent (n = 16) of patients noticed at least a little relief of pain within 5 minutes of administration and 93% (n = 26) received at least a little relief within 15 minutes. Seventy-one percent of the patients received a 50% reduction of pain within 60 minutes. No serious side effects were noted, but drowsiness occurred in 82% (n = 23) and dizziness in 54% (n = 15) of the patients. One patient discontinued participation in the study because of nausea. In this limited trial transnasal butorphanol proved to be a rapidly effective opioid analgesic. Further controlled studies comparing transnasal butorphanol with standard parenteral narcotics are needed.

Author: Ralphs-J-A. Williams-A-C. Richardson-P-H. Pither-C-E. Nicholas-M-K.

Title: Opiate reduction in chronic pain patients: a comparison of patient-controlled reduction and staff controlled cocktail methods.

Source: Pain. 1994 Mar. 56(3). P 279-88.

Journal Title: PAIN.

Abstract: This study compares the effectiveness of two methods of opiate reduction in 108 chronic pain patients during a 4 week inpatient pain management programme, and at 1-month and 6-month follow-up. Patients chose either the patient-controlled reduction (PCR) or cocktail reduction method, aiming to complete withdrawal by discharge. Use of opiates and other drugs was recorded, and psychological measures taken, at admission, at discharge, and at follow-ups. Patients who opted for the cocktail reduction method started at higher morphine equivalents (P < 0.001), were less confident in their ability to cope without medication (P < 0.05), and rated their everyday activities a more disrupted by pain (P < 0.05). At discharge, 89% of the cocktail group were abstinent from opiates compared with 68% of the PCR group (P < 0.05). By 1- month follow-up, the advantage of the cocktail method had disappeared, with no significant differences between the two groups in mean opiate dose, nor in the proportion of abstinent patients. This was the result of a greater return to opiate use in the cocktail group, with abstinence rates remaining unchanged in the PCR group. By 6-month follow-up, abstinence rates for the groups were equivalent, with 55% of patients remaining off opiates. By this stage, however, non-abstinent cocktail group patients were taking significantly larger doses of opiates than PCR patients (P < 0.05), although in both groups, the dose was well below admission level. Admission opiate dose level was the best predictor both of abstinence at discharge and of subsequent opiate dose level in non-abstinent patients. This study demonstrates that both reduction methods can produce substantial reduction in opiate use by severely impaired chronic pain patients with long medication histories.

Author: Markley-H-G.

Title: Chronic headache: appropriate use of opiate analgesics.

Source: Neurology. 1994 May. 44(5 Suppl 3). P S18-24.

Journal Title: NEUROLOGY.

Abstract: The question of the appropriate use of opiate analgesics in the management of chronic headache pain is under debate. Often, the management of headache pain is complicated by the overuse of dependency-promoting analgesics. Because of confusion about the use of analgesics in pain management, some patients are denied access to necessary opioid analgesia, whereas others receive large quantities of combination analgesics. The proper use of opiate analgesics is presented here, including a review of the pharmacology of these agents. Signs of analgesic dependence, analgesic rebound headache, and methods of withdrawal are also presented. The potential use of such new treatment modalities as butorphanol nasal spray is discussed.

Author: Andreev-N. Urban-L. Dray-A.

Title: Opioids suppress spontaneous activity of polymodal nociceptors in rat paw skin induced by ultraviolet irradiation.

Source: Neuroscience. 1994 Feb. 58(4). P 793-8.

Journal Title: NEUROSCIENCE.

Abstract: Changes in chemical sensitivity of peripheral nociceptors following injury or inflammation have been studied in in vitro preparation of the saphenous nerve-hind paw skin from adult rats. Heat hyperalgesia in the hind paw was induced by a prior ultraviolet irradiation and the skin from these animals was investigated five days later. Polymodal nociceptors were quiescent in normal skin but were spontaneously active in the majority of fibres after ultraviolet exposure. Capsaicin- induced activation of fine fibres was enhanced after ultraviolet pretreatment. Direct administration of morphine, DAGOL (mu-receptor agonist) and U-69593 (kappa-receptor agonist), but not DPDPE (delta-receptor agonist) to the receptive field produced a concentration-related and naloxone- reversible suppression of spontaneous firing in polymodal nociceptors of ultraviolet-treated skin. Morphine did not reduce the activity of fibres in normal skin when these were driven by KCl depolarization. These data show that polymodal nociceptors change their activity and sensitivity to exogenous chemicals following the induction of peripheral hyperalgesia by ultraviolet irradiation. Specifically, evidence is provided for the expression of opioid sensitivity and inhibition of polymodal nociceptor activity through mu- and kappa-opioid receptors. These observations may account for peripheral antinociceptive actions of opioids during specific states of peripheral hyperalgesia.

Author: Tyre-T-E. Walworth-D-E. Tyre-E-M.

Title: The outcome status of chronic pain patients 4 years after multidisciplinary care.

Source: Wis-Med-J. 1994 Jan. 93(1). P 9-12.


Abstract: Thirty-three patients previously treated for a variety of chronic pain syndromes (largely non-surgical back problems) were selected for study on the basis of 2 years or greater post-discharge status. A patient profile was developed revealing an 86% successful return-to-work rate and minimal use of narcotics 4 years after discharge. In addition, there was relatively low use of either inpatient or outpatient medical services after treatment. These patient behaviors were specific goals of the pain management program in which these patients had participated. Interesting data were also collected on medication use after treatment and methods of pain control used most successfully. Selected outcome variables were also studied across specific diagnostic categories (surgical v non-surgical back problems, amputee pain, reflex sympathetic dystrophy, and others) for this group. In general, rather compelling positive outcomes are shown for the long-term effects of multi-disciplinary pain management.

Author: Kehlet-H.

Title: Postoperative pain relief--what is the issue? [editorial]

Source: Br-J-Anaesth. 1994 Apr. 72(4). P 375-8.


Author: Trujillo-K-A. Akil-H.

Title: Inhibition of opiate tolerance by non-competitive N-methyl-D- aspartate receptor antagonists.

Source: Brain-Res. 1994 Jan 7. 633(1-2). P 178-88.

Journal Title: BRAIN RESEARCH.

Abstract: Our laboratory and others have previously reported that the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, interferes with the development of tolerance to the analgesic effects of morphine. The present studies were performed in order to further characterize the role of NMDA receptors in opiate tolerance. The results demonstrate that opiate tolerance is inhibited rapidly, and at low doses, by four different non-competitive NMDA receptor antagonists (MK-801, ketamine, dextrorphan and phencyclidine), suggesting that this inhibition results from blockade of NMDA receptors rather than from the 'side-effect' of a particular drug. The NMDA antagonists were found to inhibit the development but not the expression of opiate tolerance; i.e. they were able to prevent but not reverse tolerance. Finally, the results suggest that NMDA receptor antagonists do not interfere with associative tolerance; instead it appears that these drugs may specifically inhibit non-associative tolerance. It thus appears that NMDA receptors may have a fundamental role in the development of opiate tolerance, and that non- competitive NMDA receptor antagonists may be effective adjuncts to opiates in the treatment of chronic pain.

Author: Rogers-J-N. Valley-M-A.

Title: Reflex sympathetic dystrophy.

Source: Clin-Podiatr-Med-Surg. 1994 Jan. 11(1). P 73-83.


Abstract: In summary, RSD is pain of neuropathic origin. The diagnosis is often obscure and requires a complete history, physical, and psychological evaluations. The diagnosis depends on symptoms (burning pain, allodynia and hyperpathia); signs (edema, sudomotor changes, temperature changes); and objective measurements, such as skin temperature, QSART, radiographs, and triple-phase bone scans; as well as the clinical response to a sympathetic block. Management of RSD should be designed to promote restoration of function utilizing physical therapy made possible by sympathetic, central, or peripheral nerve blockade. Medications may include nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, and vasoactive drugs. Psychologic support is an important part of the patient's rehabilitation. Dorsal column or peripheral nerve stimulators, sympathectomies, and narcotics should be considered only when other more conservative measures have failed.

Author: Woodburn-S-E.

Title: Postoperative pain management.

Source: Clin-Podiatr-Med-Surg. 1994 Jan. 11(1). P 55-64.


Abstract: When surgery is planned, postoperative pain management requires careful consideration. Many medications and techniques can greatly reduce a patient's postsurgical discomfort, including nonsteroidal anti-inflammatory drugs, long-acting local anesthetics, corticosteroids, narcotics, ice, and compression. Pain management should begin preoperatively, continue through surgery, and be fully managed postoperatively. Successful management of postoperative pain greatly affects patients' overall impressions of their surgery.

Author: Tyler-D-C.

Title: Pharmacology of pain management.

Source: Pediatr-Clin-North-Am. 1994 Feb. 41(1). P 59-71.


Author: Trachtenberg-A-I.

Title: Opiates for pain: patients' tolerance and society's intolerance [letter]

Source: JAMA. 1994 Feb 9. 271(6). P 427.

Journal Title: JAMA.

Author: Andersen-G. Thomsen-A-B. Jensen-N-H. Sjogren-P.

Title: [Cerebral dysfunction after prolonged use of opioids (see comments)]

Source: Ugeskr-Laeger. 1993 Oct 25. 155(43). P 3459-62.

Comment: Comment in: Ugeskr-Laeger. 1994 Jan 10. 156(2). P 200.


Abstract: Cerebral dysfunction due to long-term treatment with opioids is a problem of increasing relevance because of the rapidly growing use of opioids. A review of psychomotor and cognitive test methods is given, including their application in patients on long-term opioid treatment. The findings of the most valid studies on cancer patients in long-term treatment with opioids are an increase in continuous reaction time and subjective sedation score regardless of the routes of administration. Studies of drug addicts in long-term treatment with opioids seem to reflect a lowering of the general level of activity. According to recent studies, patients with chronic non- malignant pain conditions are responsible for the major part of the total opioid consumption. So far, no studies of cerebral dysfunction have been performed on this group of patients. Further research should concentrate on the use of few valid psychomotor and cognitive tests and should include patients with chronic non-malignant pain conditions.

Author: Patt-R-B.

Title: Spinal opioids: distinguishing trend from science [letter; comment]

Source: J-Pain-Symptom-Manage. 1993 Oct. 8(7). P 451-3.

Comment: Comment on: J-Pain-Symptom-Manage. 1993 Jan. 8(1). P 36-46.


Author: Sees-K-L. Clark-H-W.

Title: Opioid use in the treatment of chronic pain: assessment of addiction [see comments]

Source: J-Pain-Symptom-Manage. 1993 Jul. 8(5). P 257-64.

Comment: Comment in: J-Pain-Symptom-Manage. 1994 Feb. 9(2). P 74.


Abstract: Addiction medicine specialists, besieged with the adverse consequences of opioids, not unreasonably develop reservations about their use. Opioid prohibition may be appropriate when working with addicts, but drug abstinence is not always the most appropriate nor optimal treatment of pain patients. Consultation concerning the management of chronic pain patients may require an attitude adjustment of challenging proportions for the addiction medicine specialist; it is a role substantially different from that usually assumed in treating alcohol- and drug-dependent patients. Rather than relentlessly pursuing psychotropic drug abstinence as the treatment goal, restoration of function should be the primary treatment goal for the chronic pain patient. Unlike the chemically dependent patient whose level of function is impaired by substance use, the chronic pain patient's level of function may improve with adequate, judicious use of medications, which may include opioids. Evaluating for addiction in a patient who is prescribed long-term opioids for pain control is often problematic. While the concept of addiction may include the symptoms of physical dependence and tolerance, physical dependence and/or tolerance alone does not equate with addiction. In the chronic pain patient taking long-term opioids, physical dependence and tolerance should be expected, but the maladaptive behavior changes associated with addiction are not expected. Thus, it is the presence of these behaviors in the chronic pain patient that is far more important in diagnosing addiction.

Author: Krames-E-S. Lanning-R-M.

Title: Intrathecal infusional analgesia for nonmalignant pain: analgesic efficacy of intrathecal opioid with or without bupivacaine.

Source: J-Pain-Symptom-Manage. 1993 Nov. 8(8). P 539-48.


Abstract: We report on the analgesic efficacy of intrathecal infusions of opioids alone or in combination with bupivacaine in 16 nonmalignant pain patients with implanted pumps. Three patients had nociceptive pain, five had neuropathic pain, and 8 had mixed pain syndromes. Infusional therapy was delivered over a combined monthly total of 445 mo of therapy (mean, 27.8 mo). Dose requirements appeared to be stable with a mean dose increase of 0.26 mg/mo. Bupivacaine was added to the opioid to enhance pain control in 13 patients who received combination therapy for an average of 11.7 mo/patient. Thirteen patients (81%) reported good to excellent results with opioid alone or opioid combined with bupivacaine. The addition of bupivacaine improved analgesia in two of three patients with nociceptive pain (66.7%), compared to eight of ten patients with a pure or mixed neuropathic component to their pain (80%). We conclude that intrathecal opioids alone or in combination with bupivacaine are efficacious for the treatment of nonmalignant pain states and are relatively free of significant side effects or tolerance.

Author: Joranson-D-E.

Title: Availability of opioids for cancer pain: recent trends, assessment of system barriers, New World Health Organization guidelines, and the risk of diversion.

Source: J-Pain-Symptom-Manage. 1993 Aug. 8(6). P 353-60.


Author: Clark-H-W. Sees-K-L.

Title: Opioids, chronic pain, and the law.

Source: J-Pain-Symptom-Manage. 1993 Jul. 8(5). P 297-305.


Abstract: As the United States continues its "War on Drugs," physicians who prescribe opioids for the purpose of pain control must recognize that legal issues are an important part of the prescription process. Physicians who do not correctly prescribe opioids may mark their patients as drug abusers and themselves as misprescribers. Efforts are under way to characterize appropriately the conditions under which opioids should be prescribed for the management of pain. California and Texas have passed intractable pain laws, which permit the prescribing of opioid medication for chronic pain patients. These laws were necessary because claims were made against prescribers who legitimately administered opioids to chronic pain patients. Physicians must be aware that once a patient has been diagnosed an addict, it is not legal to prescribe opioids for the purpose of maintaining or detoxifying that patient; treatment of pain is still permissible, however. It is clear that new standards of care must be developed to reduce the liability of legitimate prescribers from sanctions in either criminal or civil settings. With new standards of care, prescriptions for opioids written in good faith for the treatment of pain should survive legal scrutiny.

Author: Wesson-D-R. Ling-W. Smith-D-E.

Title: Prescription of opioids for treatment of pain in patients with addictive disease.

Source: J-Pain-Symptom-Manage. 1993 Jul. 8(5). P 289-96.


Abstract: Addiction medicine specialists and pain specialists can provide better patient care by combining their expertise when treating patients who are addicted to alcohol, street drugs, or prescription medications. Addiction specialists--particularly those whose primary treatment philosophy is drug free--must accept that controlled opiate maintenance is appropriate for some patients, and pain specialists need to increase their sensitivity to the possibility of addiction among their patients. Both pain and addiction are treatable conditions, and optimal care of some patients requires the coordinated services of both an addiction medicine specialist and a pain specialist.

Author: Schofferman-J.

Title: Long-term use of opioid analgesics for the treatment of chronic pain of nonmalignant origin.

Source: J-Pain-Symptom-Manage. 1993 Jul. 8(5). P 279-88.


Abstract: The use of long-term opioids (LTOs) to treat chronic pain of nonmalignant origin (CNMP) is controversial. Most physicians had felt there was essentially no role for LTOs in CNMP, but successful treatment outcomes have recently been reported. Tolerance, organ toxicity, or fear of addiction are not reasons to limit LTOs. The significant question is efficacy. Does LTO therapy improve pain and increase function with minimal side effects or risk? It is useful to divide chronic pain patients into three types. Type 1 patients are "typical" chronic pain patients with pain and disability far out of proportion to the peripheral stimulus. Psychological factors are significant. In this type of patient, opioids appear to do more harm than good. Type 2 patients have ongoing nociception and moderate refractory pain. Type 3 patients have refractory severe nociception or neuropathic pain. The latter types might be considered for LTOs. LTO use is appropriate for a very small, carefully selected group of patients.

Author: Gonzales-G-R. Portenoy-R-K.

Title: Selection of analgesic therapies in rheumatoid arthritis: the role of opioid medications.

Source: Arthritis-Care-Res. 1993 Dec. 6(4). P 223-8.


Author: Hamman-W.

Title: Neuropathic pain: a condition which is not always well appreciated [editorial]

Source: Br-J-Anaesth. 1993 Dec. 71(6). P 779-81.


Author: Kehlet-H. Dahl-J-B.

Title: The value of "multimodal" or "balanced analgesia" in postoperative pain treatment.

Source: Anesth-Analg. 1993 Nov. 77(5). P 1048-56.


Author: Abram-S-E.

Title: 1992 Bonica Lecture. Advances in chronic pain management since gate control.

Source: Reg-Anesth. 1993 Mar-Apr. 18(2). P 66-81.


Abstract: 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.

Author: Bowsher-D.

Title: Pain syndromes and their treatment.

Source: Curr-Opin-Neurol-Neurosurg. 1993 Apr. 6(2). P 257-63.


Abstract: Neurogenic pain (encompassing all types of neuropathic and central pain) is discussed. Experimental work is presented in a model in which the rat sciatic nerve is loosely ligatured. In painful human neuropathies, tricyclic antidepressants have been found to be effective in proportion to the degree they facilitate monoaminergic activity. Several papers also stress the importance of early treatment with amitriptyline or desipramine, and the ineffectiveness of analgesics, including narcotics. In nociceptive pain, recent findings in humans emphasize the importance of both the retroinsular (SII) and the anterior cingulate cortices in the conscious appreciation of pain. Opioid studies have revealed individual differences in the metabolism of morphine to its 3- and 6-glucuronosides; patients with nociceptive pain who respond poorly to morphine or diamorphine probably have a high 3:6 ratio. It has been pointed out that methadone may be useful in such cases, as it is not broken down to glucuronosides.

Author: Zenz-M. Willweber-Strumpf-A.

Title: Opiophobia and cancer pain in Europe [see comments]

Source: Lancet. 1993 Apr 24. 341(8852). P 1075-6.

Comment: Comment in: Lancet. 1993 Jun 5. 341(8858). P 1473-4. Comment in: Lancet. 1993 Jun 5. 341(8858). P 1474. Comment in: Lancet. 1993 Jun 5. 341(8858). P 1474-5.

Journal Title: LANCET.

Author: Garattini-S.

Title: Narcotic drug use for severe pain.

Source: Lancet. 1993 Apr 24. 341(8852). P 1061-2.

Journal Title: LANCET.

Author: Randich-A. Robertson-J-D. Willingham-T.

Title: The use of specific opioid agonists and antagonists to delineate the vagally mediated antinociceptive and cardiovascular effects of intravenous morphine.

Source: Brain-Res. 1993 Feb 19. 603(2). P 186-200.

Journal Title: BRAIN RESEARCH.

Abstract: Intravenous (i.v.) administration of morphine produces a dose- dependent inhibition of the tail-flick (TF) reflex, depressor response, and bradycardia in the rat. Some of these effects depend on interactions of i.v. morphine with peripheral opioid receptors and the integrity of cervical vagal afferents. The present studies used the relatively specific mu, delta, and kappa opioid receptor agonists (DAGO, DPDPE or U-50,488H) and the relatively specific mu, delta, and kappa opioid receptor antagonists (beta-FNA, naloxonazine, naltrindole or nor-BNI) in either intact rats or rats with bilateral cervical vagotomy (CVAG) to delineate the vagal afferent/opioid-mediated components of these effects. I.v. administration of DAGO in intact rats produced a dose-dependent inhibition of the TF reflex, depressor response, and bradycardia virtually identical to those produced by i.v. morphine. All of these effects of either i.v. DAGO or i.v. morphine were significantly attenuated by either bilateral CVAG or pre-treatment with the mu 2 opioid receptor antagonist beta-FNA. Pre-treatment with the mu 1 opioid receptor antagonist naloxonazine affected i.v. DAGO- induced inhibition of the TF reflex and bradycardia, but had no significant effects on i.v. morphine-produced responses. I.v. administration of DPDPE produced a dose-dependent pressor response, but had no marked effects on the either the TF reflex or heart rate (HR). The pressor response was unaffected by either bilateral CVAG or pre-treatment with naltrindole, naloxone, hexamethonium, or bertylium. i.v. administration of U-50,488H produced a depressor response and bradycardia, but had no significant effect on the TF reflex. The depressor response and bradycardia produced by i.v. U-50,488H were unaffected by bilateral CVAG, but could be antagonized by pre- treatment with either nor-BNI or naloxone. These studies suggest that the vagal afferent-mediated antinociceptive and cardiovascular effects of i.v. morphine are primarily mediated by interactions with low affinity mu 2 opioid receptors.

Author: Stiefel-F.

Title: Malignant and non-malignant chronic pain: therapy, opioids and fears. Swiss Centre for Paraplegia, Nottwil, 6 May 1993.

Source: Support-Care-Cancer. 1993 Sep. 1(5). P 279-80.


Author: Lossignol-D-A.

Title: Pitfalls in the use of opiates in treatment of cancer pain.

Source: Support-Care-Cancer. 1993 Sep. 1(5). P 256-8.


Abstract: The use of morphine in the treatment of cancer pain is widely accepted among people taking care of cancer patients and concerned with pain relief. Several problems regarding common side-effects, life-threatening complications in cancer and opioid-non-responsive pain syndromes will be discussed. The development of grading systems may open new directions for adequate pain control.

Author: Sosnowski-M.

Title: Pain management: physiopathology, future research and endpoints.

Source: Support-Care-Cancer. 1993 Mar. 1(2). P 79-88.


Abstract: In this article, first, the different stages of acquisition and processing of nociceptive information from peripheral receptor to brain are reviewed and the plastic changes that accompany tissue injury are underlined. For instance, the subclassification of peripheral receptors in nociceptors and non-nociceptors (e.g., mechanoreceptors, thermoreceptors) must be understood in the light of peripheral sensitization. This phenomenon is the probable explanation for primary hyperalgesia, the decrease in pain threshold at the site of injury. The observation that substance P enhances N-methyl- D-aspartate (NMDA)-elicited responses suggests that these two receptors may operate in concert to prolong and amplify the afferent input generated by peripheral tissue injury. Such afferent barrage induces a state of central sensitization. Second, the major problems in the management of cancer pain, i.e. the development of tolerance to opioids and opioid-insensitive pain, are discussed. The loss of drug effect observed after chronic exposure of the opioid receptor (tolerance) may be the consequence of the down-regulation or desensitization phenomenon (where the total number of receptors coupled to the second messenger is reduced). The agonist dose- response begins to shift to the right. The dramatic analgesic improvement obtained with subanaesthetic doses of ketamine, an NMDA receptor antagonist, in those of our cancer patients who have become resistant to morphine is intriguing. As shown for tolerance, insensitivity to opioids may represent a rightward shift in the opioid dose-response curve and the analgesic effect of ketamine the reversal of that shift.

Author: Grossman-S-A.

Title: Undertreatment of cancer pain: barriers and remedies.

Source: Support-Care-Cancer. 1993 Mar. 1(2). P 74-8.


Abstract: Over 70% of patients with cancer have moderate to severe pain during their illness and many fear pain more than death itself. There is consensus among experts that most patients can be well-palliated using knowledge, medications, and techniques that are readily accessible. Despite this, only a small proportion of patients with cancer pain receive adequate analgesia. Some of the barriers that interfere with the delivery of appropriate analgesia are patient-related, while others involve health-care providers. Patients frequently do not communicate the intensity of their pain to care- givers and are often hesitant to take opiates. Health-care providers receive scant teaching on cancer pain, have little awareness of pain intensity in their patients, and may be overly concerned about opiate toxicities. They lack appropriate role models in academic institutions and may be concerned about the potential for investigation by law-enforcement agencies. These obstacles can be largely overcome by (a) emphasizing the importance of pain control in cancer patients, (b) considering the etiology of pain in each patient, (c) weighing the full range of available therapeutic options, (d) ensuring that "user-friendly" opiate- equivalence information is available, (e) using pain assessment tools routinely and recording pain intensity scores in the medical record, and by (f) not being easily dissuaded from providing adequate doses of opiates for pain relief. The rationale for and current efforts in each of these areas are discussed in this review.

Author: Oliver-M. Stenn-P-G.

Title: Is there a risk for dependency with therapeutic doses of dimenhydrinate? [letter]

Source: Psychosomatics. 1993 Sep-Oct. 34(5). P 459.


Author: North-R-B.

Title: Neurosurgical procedures for chronic pain. General neurosurgical practice.

Source: Clin-Neurosurg. 1993. 40. P 182-96.


Author: Gybels-J. Kupers-R. Nuttin-B.

Title: What can the neurosurgeon offer in peripheral neuropathic pain?

Source: Acta-Neurochir-Suppl-Wien. 1993. 58. P 136-40.


Abstract: Neurosurgery has much to offer in the treatment of peripheral neuropathic pain but selection of the best procedure for a given patient remains problematic: planning of the treatment must be based on an analysis of the pathophysiological mechanism in the given case but the identification of this mechanism is often difficult. Available procedures are: 1) Nerve repair, neurolysis and nerve relocation; 2) Interventions on the sympathetic nervous system; 3) Neurostimulation; 4) Intraspinal morphine; 5) Ablative lesions. Neurosurgeons have, or should have, the necessary neuroscience background and microsurgical skills to be important partners of the team caring for patients with peripheral neuropathic pain.

Author: Brown-S-T. Bowman-J-M. Eason-F-R.

Title: A comparison of patient-controlled analgesia versus traditional intramuscular analgesia in postoperative pain management.

Source: J-Intraven-Nurs. 1993 Nov-Dec. 16(6). P 333-8.


Abstract: A retrospective chart review of the 198 postoperative subjects (patient-controlled analgesia [PCA] group = 100 and non-PCA group = 98) comparing analgesic usage and other variables was conducted. The PCA group used significantly more medication during the first 24 hours postoperatively and patients required more analgesic when a greater number of secondary diagnoses existed. No significant differences were found in length of stay or documentation.

Author: Kamerling-S-G.

Title: Narcotics and local anesthetics.

Source: Vet-Clin-North-Am-Equine-Pract. 1993 Dec. 9(3). P 605-20.


Abstract: The recognition and alleviation of animal pain is a growing veterinary and public concern. Pain can be of an acute or chronic nature with different behavioral manifestations. Physiologically, pain is a dynamic and complex phenomenon that produces changes in the central and autonomic nervous systems as well as in the endocrine system. Horses and other animals appear to possess an endogenous pain-suppressing system involving the brainstem and spinal cord. This system can modulate pain perception and the responses to it. The recently discovered endogenous opioid peptides (endorphins and enkephalins) appear to play a role in this system, which is activated by stress. Opioids (narcotic analgesics) act to selectively depress pain- sensitive cells. Opioid analgesics may act via multiple opioid receptors. Each subclass of opioid receptor has a different pharmacologic profile. Classical opioids that act at mu (morphine) receptors typically produce analgesia, increased locomotor activity, cardiorespiratory stimulation, and a decrease in intestinal peristalsis in the horse. Opioids that act at kappa receptors produce analgesia, sedation, ataxia, and minimal autonomic effects in the horse. Owing to their lack of excitatory actions, the kappa opioids represent a potentially useful class of analgesics for use in equine species. Local anesthetics depress all excitable cells and can diminish sensory, motor, and muscular function. They do not act selectively on pain fibers, although pain is among the first sensations lost following a nerve block. Local anesthetic activity is enhanced by increased extraneuronal pH, nerve cooling, increased nervous activity, coadministration of a vasoconstrictor or hyaluronidase, delayed systemic absorption, prolonged drug metabolism, and by using agents with high lipid solubility. Procaine, lidocaine, and mepivacaine are among the most widely used and studied agents in horses. These agents and/or their metabolites can be readily detected in urine; in some cases, for prolonged periods.

Author: Krames-E-S.

Title: The chronic intraspinal use of opioid and local anesthetic mixtures for the relief of intractable pain: when all else fails! [editorial]

Source: Pain. 1993 Oct. 55(1). P 1-4.

Journal Title: PAIN.

Author: Rahman-A-F. Takahashi-M. Kaneto-H.

Title: Development of tolerance to morphine antinociception in mice treated with nociceptive stimulants.

Source: Jpn-J-Pharmacol. 1993 Sep. 63(1). P 59-64.


Abstract: We have examined whether or not the presence of pain can block the development of tolerance to morphine antinociception in mice. A single injection of formalin or Freund complete adjuvant into the dorsal part of one side of the hind paw resulted in a significant swelling of the treated paw which lasted more than 5 days. In formalin-treated animals that received the initial morphine 2 hr after the stimulant, the development of tolerance to morphine was delayed without affecting morphine antinociception when the effect was measured daily by the tail-pinch (TP) method but not by the tail-flick (TF) method. However, the stimulant suppressed tolerance development even in the TF method unless the daily measurement was undertaken. When morphine injection was started from 5 days after the formalin injection, tolerance developed in a pattern similar to that in the control animals. On the other hand, treatment with Freund adjuvant did not affect the development of tolerance measured by both the TP and TF methods, with or without daily measurement of antinociception. When acetic acid was used as a stimulant, daily morphine was administered before or after the acetic acid injection, in the presence or absence of pain, tolerance developed to the same extent as in the control group, regardless of the time of morphine injection. Thus, our results suggest that the development of tolerance to narcotics may be modified by various factors, such as the type and intensity of nociception; and they also suggest that different results may be produced depending on the test method.

Author: Kim-T. Kim-J. Kim-S.

Title: Extended-release formulation of morphine for subcutaneous administration.

Source: Cancer-Chemother-Pharmacol. 1993. 33(3). P 187-90.


Abstract: Pain arising from cancer tends to be chronic and chemotherapy of cancer pain usually requires narcotics. Most injectable narcotics, however, have short half-lives (T1/2) and require either continuous infusion or repeated frequent injections which are both inconvenient and uncomfortable. An extended-release formulation of morphine sulfate (Depo/Morphine) in a lipid-based drug- delivery system was characterized and tested in an animal model. The encapsulation efficiency was 53% +/- 4%, and the in vitro release T1/2 in human plasma at 37 degrees C was 12.1 +/- 1.1 days. Following s.c. administration of Depo/Morphine, the total amount of morphine remaining at the s.c. injection site decreased monoexponentially with a T1/2 value of 2.59 +/- 0.16 days as compared with 0.46 +/- 0.04 h following the injection of unencapsulated morphine. The morphine concentration in plasma also decreased monoexponentially with a T1/2 value of 8.33 +/- 2.13 days as compared with 0.45 +/- 0.21 h for unencapsulated morphine. Cataleptic behavior was observed in mice injected with unencapsulated morphine but not in those given an identical dose of morphine in the form of Depo/Morphine. In conclusion, Depo/Morphine has potential as an extended-release formulation of morphine and may be useful in chemotherapy of cancer pain as well as in maintenance therapy of narcotic addicts.

Author: Smithkey-J-3d.

Title: The use of narcotics in controlling patient pain.

Source: J-Pract-Nurs. 1993 Dec. 43(4). P 17-9.


Author: King-S. Caccavo-S.

Title: Will I become addicted?

Source: AARN-News-Lett. 1993 Jun. 49(6). P 32.

Journal Title: AARN NEWS LETTER.

Author: Welch-S-P. Dunlow-L-D.

Title: Antinociceptive activity of intrathecally administered potassium channel openers and opioid agonists: a common mechanism of action?

Source: J-Pharmacol-Exp-Ther. 1993 Oct. 267(1). P 390-9.


Abstract: The potassium channel openers could share a common mechanism of action with the opiates in the production of antinociception because both classes of drugs have been shown to enhance potassium efflux. The i.t. administration of the potassium channel openers diazoxide, minoxidil, and lemakalim (BRL38227) produced antinociception as measured in the tail-flick test. The ED50's were 122, 184 and 35 micrograms/mouse, respectively. Minoxidil and lemakalim (BRL 38227) were full agonists, whereas diazoxide was a partial agonist. Diazoxide-induced antinociception was blocked by the potassium channel blockers glyburide, apamin and charybdotoxin. Minoxidil- and lemakalim (i.t.)-induced antinociception was blocked totally by only glyburide. The antinociception produced by the potassium channel openers (i.t.) was blocked differentially by opiate antagonists (i.t.). The antinociceptive effects of diazoxide were blocked by nor binaltorphimine, ICI 174,864 and naloxone. Minoxidil- and lemakalim-induced antinociception was blocked by naloxone and ICI 174,864, but not by nor-binaltorphimine. Naloxone (s.c.) shifted the dose-effect curve for minoxidil to the right in a parallel manner. Morphine-induced antinociception was partially blocked by glyburide and apamin, whereas that produced by DPDPE was blocked totally by apamin. U50, 488H-induced antinociception was blocked partially by apamin. The potassium channel openers (i.t.) were not cross tolerant to morphine when measured in the tail-flick test. Apamin and glyburide precipitated "withdrawal-like" symptoms in morphine-tolerant mice. The interaction of potassium channel openers and opioids probably does not represent a direct interaction of these two classes of drugs at a similar receptor, but rather may occur via an interaction with a common second messenger system such as calcium.

Author: Bushnell-T-G. Justins-D-M.

Title: Choosing the right analgesic. A guide to selection.

Source: Drugs. 1993 Sep. 46(3). P 394-408.

Journal Title: DRUGS.

Abstract: 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.

Author: Skaer-T-L.

Title: Management of pain in the cancer patient.

Source: Clin-Ther. 1993 Jul-Aug. 15(4). P 638-49; discussion 637.


Abstract: Pain is the most common symptom experienced in patients with advanced cancer. This pain may be acute, chronic, or intermittent, and often has a definable origin, usually related to tumor recurrence and treatment. The goal of therapy is to provide patients with enough pain relief to enable them to tolerate diagnostic and therapeutic manipulations and allow them freedom of movement and choice, while limiting medication-induced adverse effects. Morphine is the medication of choice, and is available in a sustained-release oral formulation with convenient around-the-clock administration every 8 to 12 hours. Morphine can also be administered subcutaneously, intravenously, and rectally, which provides enhanced flexibility for dosing patients unable to take oral medications. The transdermal fentanyl patch may provide a convenient dosage-form alternative if oral morphine preparations are not tolerated. Some patients with advanced cancer may require other adjunctive medications such as nonsteroidal anti-inflammatory agents, tricyclic antidepressants, steroids, or benzodiazepines, as well as psychologic techniques, to assist in pain management.

Author: Xu-J-Y. Tseng-L-F.

Title: Increase of nitric oxide by L-arginine potentiates beta- endorphin- but not mu-, delta- or kappa-opioid agonist-induced antinociception in the mouse.

Source: Eur-J-Pharmacol. 1993 May 12. 236(1). P 137-42.


Abstract: L-Arginine pretreated i.c.v. produced a time- and dose- dependent potentiation of beta-endorphin-induced inhibition of the tail-flick response in ICR mice. However, the inhibition of the tail-flick response induced by morphine, DAMGO ([D- Ala2,NMePhe4,Gly5-ol]enkephalin), DPDPE ([D-Pen2,D- Pen5]enkephalin or U50,488H given i.c.v. was not potentiated by i.c.v. pretreated L-arginine. The results indicate that L- arginine selectively potentiates antinociception induced by epsilon-opioid receptor agonist, but not mu-, delta- or kappa- opioid receptor agonist. L-Arginine pretreated i.t. did not potentiate i.c.v. administered beta-endorphin-induced inhibition of the tail-flick response, indicating that the potentiating effect of L-arginine on beta-endorphin-induced antinociception is located at the supraspinal sites but not at the spinal sites.

Accession No.: 93189288.

Author: Perrot-S. Attal-N. Ardid-D. Guilbaud-G.

Title: Are mechanical and cold allodynia in mononeuropathic and arthritic rats relieved by systemic treatment with calcitonin or guanethidine?

Source: Pain. 1993 Jan. 52(1). P 41-7.

Journal Title: PAIN.

Abstract: The putative antinociceptive action of guanethidine and calcitonin systemically injected has been compared in 2 rat models of persistent experimental pain: Freund's adjuvant-induced arthritis (n = 29) and mononeuropathy induced by 4 loose ligatures around the sciatic nerve (n = 24). Guanethidine (30 mg/kg, i.v.) and calcitonin (0.125 mg, s.c.) were injected once a day over 1 week, when hyperalgesia was fully developed. The antinociceptive action was gauged using nociceptive tests based on mechanical or cold stimuli (vocalization threshold to paw pressure and struggle latency to 10 degrees C, respectively), and the score of spontaneous pain-related behavior was measured on the basis of the abnormal hind paw position. No antinociceptive action was observed in calcitonin-compared to saline-injected rats, either in arthritic or neuropathic animals. Guanethidine treatment was ineffective on hyperalgesia exhibited in arthritic rats but was able to reduce reliably and even suppress the abnormal reactions to cold stimulus in neuropathic animals. The lack of hypoalgesic action of calcitonin versus its beneficial action in bone repair, as well as the possible role(s) of the sympathetic system in neuropathic versus arthritic pain and in hyperalgesia versus physical signs of inflammation, are discussed.

Author: Walker-J-M. Bowen-W-D. Patrick-S-L. Williams-W-E. Mascarella-S-W. Bai-X. Carroll-F-I.

Title: A comparison of (-)-deoxybenzomorphans devoid of opiate activity with their dextrorotatory phenolic counterparts suggests role of sigma 2 receptors in motor function [published erratum appears in Eur J Pharmacol 1993 Jun 4;236(3):495]

Source: Eur-J-Pharmacol. 1993 Jan 26. 231(1). P 61-8.


Abstract: Three novel benzomorphans, (+)-N-benzylnormetazocine, (-)- deoxy-N-benzylnormetazocine, and (-)-deoxypentazocine were tested for their ability to produce circling behavior in rats following intranigral microinjections. Dose studies revealed the following rank order of potency: (-)-deoxypentazocine > (- )-deoxy-N-benzylnormetazocine > (+)-N-benzylnormetazocine. This rank order approximates that for affinities for sigma 2 receptors but not sigma 1 receptors. It is very unlikely that the effects of the (-)-deoxybenzomorphans were mediated by opiate receptors for the following reasons: (1) consistent with the known requirement for the phenolic hydroxyl group for opiate activity, both (-)-deoxy compounds showed very low affinity for opiate receptors; (2) naloxone (4 micrograms) co- administered with (-)-deoxy-N-benzylnormetazocine failed to reduce its efficacy; (3) both (-)-deoxy compounds failed to produce marked analgesic effects in the tail flick test following systemic injections of 20 mg/kg s.c. These finding suggest that sigma 2 receptors mediate the motor effects of sigma ligands in rats.

Author: Stein-C.

Title: Peripheral mechanisms of opioid analgesia.

Source: Anesth-Analg. 1993 Jan. 76(1). P 182-91.


Author: Foley-K-M.

Title: Opioids.

Source: Neurol-Clin. 1993 Aug. 11(3). P 503-22.


Abstract: The major clinical uses for opioids are to control pain, suppress cough, and to treat diarrhea. These drugs, however, have the potential for abuse. It is postulated that the significant mood-altering effects of opioids combined with their pharmacology, in which tolerance and physical and psychological dependence occur, account for their abuse liability. A classification of the groups of patients that commonly present with complications of opioid use is reviewed briefly before discussing the clinical pharmacology of the opioids and their acute and toxic effects.

Author: Barsan-W-G. Tomassoni-A-J. Seger-D. Danzl-D-F. Ling-L-J. Bartlett-R.

Title: Safety assessment of high-dose narcotic analgesia for emergency department procedures.

Source: Ann-Emerg-Med. 1993 Sep. 22(9). P 1444-9.


Abstract: STUDY OBJECTIVE: To evaluate the safety of high-dose IV narcotics in patients requiring analgesia for painful emergency department procedures. DESIGN: Prospective multicenter clinical trial. SETTING: Five adult urban EDs. METHODS AND MEASUREMENTS: All patients received IV meperidine (1.5 to 3.0 mg/kg) titrated to analgesia followed by a painful procedure. Vital signs and alertness scale were recorded at regular intervals, and patients were observed for four hours. Adverse events were monitored and documented. Comparisons between baseline and postanalgesia intervals were made with a repeated measures ANOVA (Dunnett's test). RESULTS: Although statistically significant changes in vital signs and alertness scale occurred, they were not clinically significant. Opiate reversal with naloxone was not needed in any patient, and no significant respiratory or circulatory compromise occurred. CONCLUSION: This study of 72 patients demonstrates that high- dose narcotic analgesia is appropriate, well tolerated, and safe when used in selected patients before painful procedures in the ED. Narcotic antagonists and resuscitation equipment nonetheless should be available to maximize safety.

Author: Longstreth-G-F. Wolde-Tsadik-G.

Title: Irritable bowel-type symptoms in HMO examinees. Prevalence, demographics, and clinical correlates.

Source: Dig-Dis-Sci. 1993 Sep. 38(9). P 1581-9.


Abstract: A study of irritable bowel-type symptoms in 1264 health examinees using a self-administered questionnaire and psychological tests revealed they are common throughout adulthood. Of affected subjects 68% were female, and those with the more severe type (> or = 3 Manning criteria) were predominantly female (80%). Fewer Asians than other racial/ethnic groups had these symptoms. Nongastrointestinal symptoms, physician visits, incontinence, laxative use, a stress effect on bowel pattern and abdominal pain, abdominal surgery, hysterectomy, childhood abuse, use of mind- altering drugs, depression, and anxiety were correlated with irritable bowel-type symptoms. Regression analysis found some of the clinical correlates were independent markers for irritable bowel-type symptoms and that sexual abuse was related to nongastrointestinal symptoms and abdominal surgery independent of irritable bowel-type symptoms. More severe irritable bowel-type symptoms were especially associated with nongastrointestinal symptoms, stress effects, sexual abuse, use of sedatives and oral narcotics, and a past alcohol problem. There are important demographic and clinical correlates with irritable bowel-type symptoms.

Author: MacDonald-N. Der-L. Allan-S. Champion-P.

Title: Opioid hyperexcitability: the application of alternate opioid therapy.

Source: Pain. 1993 Jun. 53(3). P 353-5.

Journal Title: PAIN.

Abstract: Three cases are reported where patients experienced severe central nervous system adverse effects on high-dose hydromorphone. These effects were rapidly alleviated following a change in therapy to morphine at 20-25% of the usually accepted potency equivalent dose. We recommend caution in using equivalent dose tables when changing opioid therapy in patients receiving high-dose opioid treatment.

Author: Chrubasik-J. Martin-E. Chrubasik-S. Friedrich-G. Black-A.

Title: Epidural opioids for treatment of acute pain: a question of dose? [letter]

Source: Pain. 1993 May. 53(2). P 237-9.

Journal Title: PAIN.

Author: Draznin-E. Rosenberg-N-L.

Title: Intensive rehabilitative approach to eosinophilia myalgia syndrome associated with severe polyneuropathy.

Source: Arch-Phys-Med-Rehabil. 1993 Jul. 74(7). P 774-6.


Abstract: We report a case of the eosinophilia myalgia syndrome (EMS) with incapacitating myalgias, weakness secondary to a severe polyneuropathy, and contractures in all four extremities requiring aggressive rehabilitation treatment. A 55-year-old woman was admitted to a rehabilitation hospital 11 months after the onset of EMS. At that time, she had severe weakness secondary to peripheral neuropathy and painful contractures in all extremities and required high doses of narcotics for pain control. A continuous passive range of motion machine was used in order to maintain range of motion obtained during active exercise therapy. The patient showed functional improvement in basic mobility and ADL skills. She was withdrawn from narcotics and successfully learned pain management techniques. An aggressive rehabilitation approach in the treatment of EMS associated with peripheral neuropathy may improve functional outcome even when instituted late in the clinical course.

Author: Tobias-J-D.

Title: Management of minor adverse effects encountered during narcotic administration.

Source: J-Post-Anesth-Nurs. 1993 Apr. 8(2). P 96-100.


Abstract: Presented are four clinical scenarios of patients receiving narcotics to control pain of various etiologies. In all cases minor adverse effects necessitated intervention so that continued use of these agents was possible. The four cases illustrate common adverse effects, including nausea, vomiting, pruritus, and dysphoria, that may occur during narcotic administration. Management strategies to deal with these and other common non-life-threatening effects of narcotic agents are presented.

Author: Landau-B. Levy-R-M.

Title: Neuromodulation techniques for medically refractory chronic pain.

Source: Annu-Rev-Med. 1993. 44. P 279-87.


Abstract: Advances in our knowledge of the physiology of pain transmission and modulation have created new surgical options for the control of chronic pain. The pain modulation network can be activated by administration of spinal opiates or by electrical stimulation of the nervous system with transcutaneous, peripheral nerve, spinal cord, and deep brain stimulation. The theoretical basis and the clinical applications of neurostimulation for the treatment of medically intractable chronic pain are reviewed.

Author: McCarthy-M-R. Yates-C-K. Anderson-M-A. Yates-McCarthy-J-L.

Title: The effects of immediate continuous passive motion on pain during the inflammatory phase of soft tissue healing following anterior cruciate ligament reconstruction.

Source: J-Orthop-Sports-Phys-Ther. 1993 Feb. 17(2). P 96-101.


Abstract: Continuous passive motion (CPM) may have potential application as a physical modality in decreasing acute pain. The purpose of this study was to examine the effects of CPM immediately following an arthroscopically-assisted anterior cruciate ligament (ACL) reconstruction utilizing bone-patella- bone autograft on acute pain during the inflammatory phase of soft tissue healing. Acute pain was measured by assessing the amount of pain medication (amount of narcotic delivered from the patient-controlled analgesia (PCA) pump during the first postoperative 24 hours and the total intake of oral medication during the second and third postoperative days), the need for pain medication (number of times the patient pushed the PCA button during the first postoperative 24 hours), and perceived pain (graphic pain scale measuring antalgic sensation). Thirty patients (15-45 years old) participated in this study. The patients were prospectively randomized into two groups, CPM and non-CPM. Both groups followed an identical postoperative rehabilitation program except for the CPM groups using a CPM device. The design of this study included the collection of data during the inflammatory phase of soft tissue healing. The results indicated that the initiation of CPM immediately following an ACL reconstruction had a significant (p < .05) effect on decreasing the amount of medication consumed by the patient and a significant (p < .05) decrease in the patient's need for medication during the inflammatory phase. There was no statistical significance in the level of perceived pain between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

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