Buprenorphine—A review of its role in neuropathic pain

Authors

  • Guy Hans, MD

DOI:

https://doi.org/10.5055/jom.2007.0005

Keywords:

buprenorphine, opioids, neuropathic pain, hyperalgesia, allodynia, sensitization

Abstract

Background: The use of opioids for the treatment of neuropathic pain remains somewhat controversial, since earlier studies indicate that neuropathic pain is generally less responsive to pure μ-opioid analgesia. A growing body of evidence now suggests that different opioids affect different pain pathways, and emerging data support the possibility of a role for buprenorphine in the management of neuropathic pain.
Objective: This article reviews the preclinical and clinical data for the role of buprenorphine in the treatment of neuropathic pain.
Research Design and Methods: Literature searches were carried out using PubMed (1988 to September 2006). Search terms included buprenorphine and neuropathic pain, as well as neuropathy, painful neuropathy, hyperalgesia, and allodynia. Clinical studies and case studies were included.
Results: Several assays, including the formalin, cold tail flick, and diffuse noxious inhibitory control tests, have revealed buprenorphine’s potential efficacy in various pain types. These findings seem to support hypotheses regarding its unique analgesic mechanisms as compared with pure μ-opioids. The exact mechanism of this analgesic efficacy remains unknown. Preclinical assessments of buprenorphine demonstrate its sustained antihyperalgesic effect in several models of neuropathic pain. These findings are supported in clinical studies of oral, intrathecal, intravenous, and transdermal buprenorphine. Furthermore, these studies have demonstrated that, despite there being a ceiling effect for respiratory depression, no relevant analgesic ceiling effect is found with buprenorphine.
Conclusions: Further studies are certainly warranted to identify the clinical neuropathic syndromes that are most sensitive to buprenorphine treatment, and to compare buprenorphine with other opioids in head-to-head trials of neuropathic pain.

Author Biography

Guy Hans, MD

Multidisciplinary Pain Center (PCT), Antwerp University Hospital (UZA), Edegem, Belgium. E-mail: guy.hans@uza.be

References

Colombo B, Annovazzi PO, Comi G: Medications for neuropathic pain: Current trends. Neurol Sci. 2006; 27 (Suppl 2): S183-S189.

McCleane G: Pharmacological strategies in relieving neuropathic pain. Expert Opin Pharmacother. 2004; 5(6): 1299-1312.

Sindrup SH, Jensen TS: Efficacy of pharmacological treatments of neuropathic pain: An update and effect related to mechanism of drug action. Pain. 1999; 83(3): 389-400.

Rasmussen PV, Sindrup SH, Jensen TS, et al.: Therapeutic outcome in neuropathic pain: Relationship to evidence of nervous system lesion. Eur J Neurol. 2004; 11(8): 545-553.

Finnerup NB, Otto M, McQuay HJ, et al.: Algorithm for neuropathic pain treatment: An evidence based proposal. Pain. 2005; 118(3): 289-305.

Arner S, Meyerson BA: Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain. 1988; 33: 11-23.

Raja S, Haythonwaite J, Pappagallo M: Opioids versus antidepressants in postherpetic neuralgia: A randomised, placebo controlled trial. Neurology. 2002; 59: 1015-1021.

Rowbotham MC: The debate over opioids and neuropathic pain. In Kalso E, McQuay HJ, Wiesenfeld-Hallin Z (eds.): Opioid Sensitivity of Noncancer Pain–Progress in Pain Research and Management. vol. 14. Seattle: IASP Press, 1999: 307-317.

Guirguis-Blake J, Kelly C: Are opioids effective in the treatment of neuropathic pain? Am Fam Physician. 2007; 75(7): 999-1001.

Rowbotham MC, Twilling L, Davies PS, et al.: Oral opioid therapy for chronic peripheral and central neuropathic pain. N Engl J Med. 2003; 348(13): 1223-1232.

Eisenberg E, McNicol E, Carr DB: Opioids for neuropathic pain. Cochrane Database Syst Rev. 2006; 19(3): CD006146.

Furlan AD, Sandoval JA, Mailis-Gagnon A, et al.: Opioids for chronic noncancer pain: A meta-analysis of effectiveness and side effects. CMAJ. 2006; 174(11): 1589-1594.

Budd K: Buprenorphine: A Review. Evidence Based Medicine in Practice. Newmarket: Hayward Medical Communications, 2002.

Cowan A, Friderichs E, Straßurger W, et al.: Basic pharmacology of buprenorphine. In Budd K, Raffa RB (eds.): Buprenorphine–The Unique Opioid Analgesic: Pharmacology and Clinical Application. Stuttgart: George Thieme Verlag KG, 2005: 3-21.

Portenoy RK, Foley KM, Inturrisi CE: The nature of opioid responsiveness and its implications for neuropathic pain: New hypotheses derived from studies of opioid infusions. Pain. 1990; 43(3): 273-286.

Wall PD: Neuropathic pain. Pain. 1990; 43(3): 267-268.

Dellemijn P: Are opioids effective in relieving neuropathic pain? Pain. 1999; 80(3): 453-462.

Jackson KC II. Pharmacotherapy for neuropathic pain. Pain Pract. 2006; 6(1): 27-33.

Jadad AR, Carroll D, Glynn CJ, et al.: Morphine responsiveness of chronic pain: Double-blind randomised crossover study with patient-controlled analgesia. Lancet. 1992; 339(8806): 1367-1371.

Davis MP: What is new in neuropathic pain? Support Care Cancer. 2007; 15(4): 363-372.

Eisenberg E, McNicol E, Carr DB: Opioids for neuropathic pain. Cochrane Database Syst Rev. 2006; 3: CD006146.

Watson CP, Watt-Watson JH, Chipman ML: Chronic noncancer pain and the long term utility of opioids. Pain Res Manag. 2004 Spring; 9(1): 19-24.

Gagnon B, Almahrezi A, Schreier G: Methadone in the treatment of neuropathic pain. Pain Res Manag. 2003 Fall; 8(3): 149-154.

Morley JS, Bridson J, Nash TP, et al.: Low-dose methadone has an analgesic effect in neuropathic pain: A double-blind randomized controlled crossover trial. Palliat Med. 2003; 17(7): 576-587.

Moulin DE, Palma D, Watling C, et al.: Methadone in the management of intractable neuropathic noncancer pain. Can J Neurol Sci. 2005; 32(3): 340-343.

Watson CP, Moulin D, Watt-Watson J, et al.: Controlledrelease oxycodone relieves neuropathic pain: A randomized controlled trial in painful diabetic neuropathy. Pain. 2003; 105(1/2): 71-78.

Eisenberg E, McNicol ED, Carr DB: Efficacy of μ-opioid agonists in the treatment of evoked neuropathic pain: Systematic review of randomized controlled trials. Eur J Pain. 2006; 10: 667-676.

Cowan A, Lewis JW, Macfarlane IR: Agonist and antagonist properties of buprenorphine, a new antinociceptive agent. Br J Pharmacol. 1977; 60(4): 537-545.

McCormack K, Prather P, Chapleo C: Some new insights into the effects of opioids in phasic and tonic nociceptive tests. Pain. 1998; 78(2): 79-98.

Pick CG, Peter Y, Schreiber S, et al.: Pharmacological characterization of buprenorphine, a mixed agonist-antagonist with ϰ3 analgesia. Brain Res. 1997; 744(1): 41-46.

Schreiber S, Backer MM, Yanai J, et al.: The antinociceptive effect of fluvoxamine. Eur Neuropsychopharmacol. 1996; 6(4): 281-284.

McLaughlin CR, Tao Q, Abood ME: Analysis of the antinociceptive actions of the ϰ-opioid agonist enadoline (CI-977) in neonatal and adult rats: Comparison to ϰ-opioid receptor mRNA ontogeny. Drug Alcohol Depend. 1995; 38(3): 261-269.

Sanchez JA, Gonoi T, Inagaki N, et al.: Modulation of reconstituted ATP-sensitive K(+)-channels by GTP-binding proteins in a mammalian cell line. J Physiol. 1998; 507 (Part 2): 315-324.

Wada Y, Yamashita T, Imai K, et al.: A region of the sulfonylurea receptor critical for a modulation of ATP-sensitive K(+) channels by G-protein βγ-subunits. EMBO J. 2000; 19(18): 4915-4925.

Mark MD, Herlitze S: G-protein mediated gating of inwardrectifier K+ channels. Eur J Biochem. 2000; 267(19): 5830-5836.

Ocana M, Del Pozo E, Barrios M, et al.: Subgroups among μ-opioid receptor agonists distinguished by ATP-sensitive K+ channel-acting drugs. Br J Pharmacol. 1995; 114(6): 1296-1302.

Wood JN, Abrahamsen B, Baker MD, et al.: Ion channel activities implicated in pathological pain. Novartis Found Symp. 2004; 261: 32-40; Discussion 40-54.

Yang EK, Takimoto K, Hayashi Y, et al.: Altered expression of potassium channel subunit mRNA and -dendrotoxin sensitivity of potassium currents in rat dorsal root ganglion neurons after axotomy. Neuroscience. 2004; 123(4): 867-874.

Bloms-Funke P, Gillen C, Schuettler AJ, et al.: Agonistic effects of the opioid buprenorphine on the nociceptin/OFQ receptor. Peptides. 2000; 21(7): 1141-1146.

Hawkinson JE, Acosta-Burruel M, Espitia SA: Opioid activity profiles indicate similarities between the nociceptin/orphanin FQ and opioid receptors. Eur J Pharmacol. 2000; 389(2/3): 107-114.

Huang P, Kehner GB, Cowan A, et al.: Comparison of pharmacological activities of buprenorphine and norbuprenorphine: Norbuprenorphine is a potent opioid agonist. J Pharmacol Exp Ther. 2001; 297(2): 688-695.

Wnendt S, Kruger T, Janocha E, et al.: Agonistic effect of buprenorphine in a nociceptin/OFQ receptor-triggered reporter gene assay. Mol Pharmacol. 1999; 56(2): 334-338.

Lutfy K, Eitan S, Bryant CD, et al.: Buprenorphine-induced antinociception is mediated by μ-opioid receptors and compromised by concomitant activation of opioid receptor-like receptors. J Neurosci. 2003; 23(32): 10331-10337.

Hentz JG, Valle-Robillart A, Franckhauser J, et al.: The use of intrathecal morphine in thoracic anesthesia. J Cardiothorac Anesth. 1989; 3 (5 Suppl 1): 24.

Lundborg CN, Nitescu PV, Appelgren LK, et al.: Progressive systemic sclerosis: Intrathecal pain management. Reg Anesth Pain Med. 1999 Jan-Feb; 24(1): 89-93.

Nitescu P, Dahm P, Appelgren L, et al.: Continuous infusion of opioid and bupivacaine by externalized intrathecal catheters in long-term treatment of “refractory” nonmalignant pain. Clin J Pain. 1998; 14(1): 17-28.

Tejwani GA, Rattan AK: The role of spinal opioid receptors in antinociceptive effects produced by intrathecal administration of hydromorphone and buprenorphine in the rat. Anesth Analg. 2002; 94(6): 1542-1546.

Guirimand F, Chauvin M, Willer JC, et al.: Effects of intrathecal and intracerebroventricular buprenorphine on a C-fiber reflex in the rat. J Pharmacol Exp Ther. 1995; 275(2): 629-637.

Inagaki Y, Mashimo T, Yoshiya I: Mode and site of analgesic action of epidural buprenorphine in humans. Anesth Analg. 1996; 83(3): 530-536.

McLaughlin CR, Dewey WL: A comparison of the antinociceptive effects of opioid agonists in neonatal and adult rats in phasic and tonic nociceptive tests. Pharmacol Biochem Behav. 1994; 49(4): 1017-1023.

Guirimand F, Chauvin M, Willer JC, et al.: Buprenorphine blocks diffuse noxious inhibitory controls in the rat. Eur J Pharmacol. 1995; 294(2/3): 651-659.

Kakigi R: Diffuse noxious inhibitory control. Reappraisal by pain-related somatosensory evoked potentials following CO2 laser stimulation. J Neurol Sci. 1994; 125(2): 198-205.

Le Bars D, Chitour D, Kraus E, et al.: The effect of systemic morphine upon diffuse noxious inhibitory controls (DNIC) in the rat: Evidence for a lifting of certain descending inhibitory controls of dorsal horn convergent neurones. Brain Res. 1981; 215(1/2): 257-274.

Ciruela A, Dixon AK, Bramwell S, et al.: Identification of MEK1 as a novel target for the treatment of neuropathic pain. Br J Pharmacol. 2003; 138: 751-756.

Jin SX, Zhuang ZY, Woolf CJ, et al.: p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J Neurosci. 2003; 23(10): 4017-4022.

Milligan ED, Twining C, Chacur M, et al.: Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats. J Neurosci. 2003; 23(3): 1026-1040.

Womer DE, DeLapp NW, Shannon HE: Intrathecal pertussis toxin produces hyperalgesia and allodynia in mice. Pain. 1997; 70(2/3): 223-228.

Wheeler-Aceto H, Cowan A: Buprenorphine and morphine cause antinociception by different transduction mechanisms. Eur J Pharmacol. 1991; 195(3): 411-413.

Wang JJ, Ho ST, Hu OY, et al.: An innovative cold tail-flick test: The cold ethanol tail-flick test. Anesth Analg. 1995; 80(1): 102-107.

Kouya PF, Hao JX, Xu XJ: Buprenorphine alleviates neuropathic pain-like behaviors in rats after spinal cord and peripheral nerve injury. Eur J Pharmacol. 2002; 450(1): 49-53.

Xu XJ, Hao JX, Aldskogius H, et al.: Chronic pain-related syndrome in rats after ischemic spinal cord lesion: A possible animal model for pain in patients with spinal cord injury. Pain. 1992; 48(2): 279-290.

Yu W, Hao JX, Xu XJ, et al.: Comparison of the antiallodynic and antinociceptive effects of systemic; intrathecal and intracerebroventricular morphine in a rat model of central neuropathic pain. Eur J Pain. 1997; 1(1): 17-29.

Kupers R, Yu W, Persson JK, et al.: Photochemically-induced ischemia of the rat sciatic nerve produces a dose-dependent and highly reproducible mechanical, heat and cold allodynia, and signs of spontaneous pain. Pain. 1998; 76(1/2): 45-59.

Bulka A, Plesan A, Xu XJ, et al.: Reduced tolerance to the antihyperalgesic effect of methadone in comparison to morphine in a rat model of mononeuropathy. Pain. 2002; 95: 103-109.

Stewart LS, Martin WJ: Influence of postoperative analgesics on the development of neuropathic pain in rats. Comp Med. 2003; 53(1): 29-36.

Christoph T, Kogel B, Schiene K, et al.: Broad analgesic profile of buprenorphine in rodent models of acute and chronic pain. Eur J Pharmacol. 2005; 507: 87-98.

Koppert W, Ihmsen H, Korber N, et al.: Different profiles of buprenorphine-induced analgesia and antihyperalgesia in a human pain model. Pain. 2005; 118(1/2): 15-22.

Sittl R: Transdermal buprenorphine in the treatment of chronic pain. Expert Rev Neurother. 2005; 5(3): 315-323.

Staats P, Johnson R: New perspectives on the pharmacology of opioids and their use in chronic pain. Prog Anaesthesiol. 2002; 16: 235-249.

Likar R: Transdermal buprenorphine in the management of persistent pain–Safety aspects. Ther Clin Risk Manag. 2006; 2(1): 115-125.

Walsh SL, Preston KL, Stitzer ML, et al.: Clinical pharmacology of buprenorphine: Ceiling effects at high doses. Clin Pharmacol Ther. 1994; 55(5): 569-580.

Böhme K: Buprenorphine in a transdermal therapeutic system–A new option. Clin Rheumatol. 2002; 21 (Suppl 1): S13-S16.

Johnson RE, Fudala PJ, Payne R: Buprenorphine: Considerations for pain management. J Pain Symptom Manage. 2005; 29(3): 297-326. 74. Dahan A: Opioid-induced respiratory effects: New data on buprenorphine. Palliat Med. 2006; 20 (Suppl 1): s3-s8.

Zenz M, Strumpf M, Tryba M: Long-term oral opioid therapy in patients with chronic nonmalignant pain. J Pain Symptom Manage. 1992; 7(2): 69-77.

Omote K, Ohmori H, Kawamata M, et al.: Intrathecal buprenorphine in the treatment of phantom limb pain. Anesth Analg. 1995; 80(5): 1030-1032.

Gotoda Y, Kambara N, Sakai T, et al.: The morbidity, time course and predictive factors for persistent post-thoracotomy pain. Eur J Pain. 2001; 5(1): 89-96.

Benedetti F, Vighetti S, Amanzio M, et al.: Dose-response relationship of opioids in nociceptive and neuropathic postoperative pain. Pain. 1998; 74: 205-211.

Kalia YN, Merino V, Guy RH: Transdermal drug delivery. Clinical aspects. Dermatol Clin. 1998; 16(2): 289-299.

Sittl R, Griessinger N, Likar R: Analgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer and other disorders: A multicenter, randomized, double-blind, placebo-controlled trial. Clin Ther. 2003; 25(1): 150-168.

Sorge J, Sittl R: Transdermal buprenorphine in the treatment of chronic pain: Results of a phase III, multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2004; 26(11): 1808-1820.

Likar R, Kayser H, Sittl R: Long-term management of chronic pain with transdermal buprenorphine: A multicenter, openlabel, follow-up study in patients from three short-term clinical trials. Clin Ther. 2006; 28(6): 943-952.

Rodriguez-Lopez M: Transdermal buprenorphine in the treatment of neuropathic pain. Rev Soc Esp Dolor. 2004; 11: S11-S21.

Likar R, Sittl R: Transdermal buprenorphine for treating nociceptive and neuropathic pain: Four case studies. Anesth Analg. 2005; 100(3): 781-785.

Louis F: Transdermal buprenorphine in pain management– Experiences from clinical practice: Five case studies. Int J Clin Pract. 2006; 60(10): 1330-1334.

Griessinger N, Sittl R, Likar R: Transdermal buprenorphine in clinical practice–A post-marketing surveillance study in 13,179 patients. Curr Med Res Opin. 2005; 21(8): 1147-1156.

Radbruch L, Sabatowski R, Petzke F, et al.: Transdermal fentanyl for the management of cancer pain: A survey of 1005 patients. Palliat Med. 2001; 15(4): 309-321.

Sittl R, Likar R, Nautrup BP: Equipotent doses of transdermal fentanyl and transdermal buprenorphine in patients with cancer and noncancer pain: Results of a retrospective cohort study. Clin Ther. 2005; 27(2): 225-237.

Sittl R, Nuijten M, Nautrup BP: Patterns of dosage changes with transdermal buprenorphine and transdermal fentanyl for the treatment of noncancer and cancer pain: A retrospective data analysis in Germany. Clin Ther. 2006; 28(8): 1144-1154.

Dertwinkel R, Donner B, Zenz M, Schulz S, Bading B: Opioids in chronic pain. Baillère’s Clin Anaesthesiol. 1998; 12(1): 39-52.

Doxey J, Everitt J, Frank L, et al.: A comparison of the effects of buprenorphine and morphine on the blood gases of conscious rats. Brit J Pharmacol. 1982; 75: 118P.

Dahan A, Yassen A, Bijl H, et al.: Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats. Br J Anaesth. 2005; 94(6): 825-834.

van Dorp E, Yassen A, Sarton E, et al.: Naloxone reversal of buprenorphine-induced respiratory depression. Anesthesiology. 2006; 105(1): 51-57.

Published

07/01/2007

How to Cite

Hans, MD, G. “Buprenorphine—A Review of Its Role in Neuropathic Pain”. Journal of Opioid Management, vol. 3, no. 4, July 2007, pp. 195-06, doi:10.5055/jom.2007.0005.

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