Background Although opioids are commonly used to treat chronicneuropathic pain, there are limited data to guide their use.Few controlled trials have been performed, and many types ofneuropathic pain remain unstudied.
Methods Adults with neuropathic pain that was refractory totreatment were randomly assigned to receive either high-strength(0.75-mg) or low-strength (0.15-mg) capsules of the potent µ-opioidagonist levorphanol for eight weeks under double-blind conditions.Intake was titrated by the patient to a maximum of 21 capsulesof either strength per day. Outcome measures included the intensityof pain as recorded in a diary, the degree of pain relief, qualityof life, psychological and cognitive function, the number ofcapsules taken daily, and blood levorphanol levels.
Results Among the 81 patients exposed to the study drug, high-strengthlevorphanol capsules reduced pain by 36 percent, as comparedwith a 21 percent reduction in pain in the low-strength group(P=0.02). On average, patients in the high-strength group took11.9 capsules per day (8.9 mg per day) and patients in the low-strengthgroup took close to the 21 allowed (18.3 capsules per day; 2.7mg per day). Affective distress and interference with functioningwere reduced, and sleep was improved, but there were no differencesbetween the high-strength group and the low-strength group interms of these variables. Noncompletion of the study was primarilydue to side effects of the opioid. Patients with central painafter stroke were the least likely to report benefit.
Conclusions The reduction in the intensity of neuropathic painwas significantly greater during treatment with higher dosesof opioids than with lower doses. Higher doses produced moreside effects without significant additional benefit in termsof other outcome measures.
Source Information
From the Pain Clinical Research Center, Department of Neurology (M.C.R., L.T., P.S.D., L.R., K.T., D.M.), and the Department of Anesthesia (M.C.R.), University of California, San Francisco, School of Medicine; and the University of California, San Francisco, School of Pharmacy (L.R.) all in San Francisco.
Address reprint requests to Dr. Rowbotham at the Pain Clinical Research Center, 1701 Divisadero St., Ste. 480, San Francisco, CA 94115.
Galluzzi, K. E.
(2007). Managing Neuropathic Pain. JAOA: Journal of the American Osteopathic Association
107: ES39-ES48
[Abstract][Full Text]
Abrams, D. I., Jay, C. A., Shade, S. B., Vizoso, H., Reda, H., Press, S., Kelly, M. E., Rowbotham, M. C., Petersen, K. L.
(2007). Cannabis in painful HIV-associated sensory neuropathy: A randomized placebo-controlled trial. Neurology
68: 515-521
[Abstract][Full Text]
Lindgren, I., Jonsson, A.-C., Norrving, B., Lindgren, A.
(2007). Shoulder Pain After Stroke: A Prospective Population-Based Study. Stroke
38: 343-348
[Abstract][Full Text]
VADALOUCA, A., SIAFAKA, I., ARGYRA, E., VRACHNOU, E., MOKA, E.
(2006). Therapeutic Management of Chronic Neuropathic Pain: An Examination of Pharmacologic Treatment. Ann. N. Y. Acad. Sci.
1088: 164-186
[Abstract][Full Text]
Porreca, F., Vanderah, T. W., Guo, W., Barth, M., Dodey, P., Peyrou, V., Luccarini, J. M., Junien, J.-L., Pruneau, D.
(2006). . J. Pharmacol. Exp. Ther.
318: 195-205
[Abstract][Full Text]
Somers, D. L, Clemente, F R.
(2006). Transcutaneous Electrical Nerve Stimulation for the Management of Neuropathic Pain: The Effects of Frequency and Electrode Position on Prevention of Allodynia in a Rat Model of Complex Regional Pain Syndrome Type II. ptjournal
86: 698-709
[Abstract][Full Text]
Sinatra, R.
(2006). Opioid Analgesics in Primary Care: Challenges and New Advances in the Management of Noncancer Pain. J Am Board Fam Med
19: 165-177
[Abstract][Full Text]
Rowbotham, M. C.
(2005). Mechanisms of neuropathic pain and their implications for the design of clinical trials. Neurology
65: S66-S73
[Abstract][Full Text]
Wu, H.-E., Thompson, J., Sun, H.-S., Terashvili, M., Tseng, L. F.
(2005). Antianalgesia: Stereoselective Action of dextro-Morphine over levo-Morphine on Glia in the Mouse Spinal Cord. J. Pharmacol. Exp. Ther.
314: 1101-1108
[Abstract][Full Text]
Galluzzi, K. E.
(2005). Management of Neuropathic Pain. JAOA: Journal of the American Osteopathic Association
105: S12-S19
[Abstract][Full Text]
Eisenberg, E., McNicol, E. D., Carr, D. B.
(2005). Efficacy and Safety of Opioid Agonists in the Treatment of Neuropathic Pain of Nonmalignant Origin: Systematic Review and Meta-analysis of Randomized Controlled Trials. JAMA
293: 3043-3052
[Abstract][Full Text]
Buntin-Mushock, C., Phillip, L., Moriyama, K., Palmer, P. P.
(2005). Age-Dependent Opioid Escalation in Chronic Pain Patients. Anesth. Analg.
100: 1740-1745
[Abstract][Full Text]
Likar, R., Sittl, R.
(2005). Transdermal Buprenorphine for Treating Nociceptive and Neuropathic Pain: Four Case Studies. Anesth. Analg.
100: 781-785
[Abstract][Full Text]
Rubey, R. N.
(2005). Treatment of chronic pain in persons with dementia: An overview. AM J ALZHEIMERS DIS OTHER DEMEN
20: 12-20
[Abstract]
Ji, R.-R., Strichartz, G.
(2004). Cell Signaling and the Genesis of Neuropathic Pain. Sci Signal
2004: re14-re14
[Abstract][Full Text]
Lussier, D., Huskey, A. G., Portenoy, R. K.
(2004). Adjuvant Analgesics in Cancer Pain Management. The Oncologist
9: 571-591
[Abstract][Full Text]
Ballantyne, J. C.
(2003). Chronic Pain Following Treatment for Cancer: The Role of Opioids. The Oncologist
8: 567-575
[Abstract][Full Text]
Ballantyne, J. C., Mao, J.
(2003). Opioid Therapy for Chronic Pain. NEJM
349: 1943-1953
[Full Text]
Dworkin, R. H., Backonja, M., Rowbotham, M. C., Allen, R. R., Argoff, C. R., Bennett, G. J., Bushnell, M. C., Farrar, J. T., Galer, B. S., Haythornthwaite, J. A., Hewitt, D. J., Loeser, J. D., Max, M. B., Saltarelli, M., Schmader, K. E., Stein, C., Thompson, D., Turk, D. C., Wallace, M. S., Watkins, L. R., Weinstein, S. M.
(2003). Advances in Neuropathic Pain: Diagnosis, Mechanisms, and Treatment Recommendations. Arch Neurol
60: 1524-1534
[Abstract][Full Text]
Canavero, S., Bonicalzi, V., Simpson, J. K. III, Foley, K. M.
(2003). Chronic Neuropathic Pain. NEJM
348: 2688-2689
[Full Text]