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Anti-allodynic Effect of Nefopam and Morphine in a Rat Model of Neuropathic Pain

Taraneh Moini Zanjani, Elham Saghaei, Haleh Ameli, Masoumeh Sabetkasaei
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Abstract

Please cite this article as: Moini Zanjani T, Saghaei E, Ameli H, Sabetkasaei M. Anti-allodynic Effect of Nefopam and Morphine in a Rat Model of Neuropathic Pain. Novel Biomed 2013;1:16-22.

Background: Neuropathic pain is a chronic pain due to a disorder in the peripheral or central nervous system with different pathophysiological mechanisms. Current treatments are not effective. Here we compared the analgesic effect of nefopam, and morphine in chronic constriction injury (CCI) model of neuropathic pain.


Methods: Male wistar rat (150-200g, n=8) were divided into 3 different groups: 1- Saline-treated CCI group, 2- Saline-treated sham group, and 3- Drug-treated CCI groups. In CCI model of neuropathic pain, the left sciatic nerve was exposed and 4 loose chromic gut ligatures were placed around the nerve proximal to the trifurcation. Ketamine 60mg/kg and xylazine 10 mg/kg were used for anesthesia. Nefopam (10, 20, 30mg/kg), and morphine (1, 3, 5mg/kg) were injected 30 minutes before surgery and continued daily to day 14 post-ligation. Von Frey filaments for mechanical allodynia and acetone test for cold allodynia were respectively used as pain behavioral tests. Experiments were performed on day 0 (before surgery) and days 1, 3, 5,7,10 and 14 post injury. Behavioral studies were performed in a quiet room between 9:00 to 11:00 AM. All experiments followed the IASP guidelines on ethical standards for investigation of experimental pain in animals.


Results: Nefopam (20 and 30mg/kg) blocked mechanical and cold allodynia during the experimental period, but the analgesic effects of morphine (5mg/kg) lasted for 7 days.


Conclusions: It seems that nefopam could effectively reduce pain behavior compared to morphine with reduced adverse effects.


Keywords

neuropathic pain; nefopam; morphine; allodynia

References

Arner S, Meyerson BA. Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain 1988;33(1):11-23.

Raja SN, Haythornthwaite JA, Pappagallo M, Clark MR, Travison TG, Sabeen S, et al. Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2002;59(7):1015-21.

Wu CL, Tella P, Staats PS, Vaslav R, Kazim DA, Wesselmann U, et al. Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized double-blind, active placebo-controlled, crossover trial. Anesthesiology 2002 Apr;96(4):841-8.

Dobecki DA, Schocket SM, Wallace MS. Update on pharmacotherapy guidelines for the treatment of neuropathic pain. Curr Pain Headache Rep 2006 Jun;10(3):185-90.

Fernandez-Sanchez MT, Diaz-Trelles R, Groppetti A, Manfredi B, Brini AT, Biella G, et al. Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity. Amino Acids 2002;23(1-3):31-6.

Durrieu G, Olivier P, Bagheri H, Montastruc JL. Overview of adverse reactions to nefopam: an analysis of the French Pharmacovigilance database. Fundam Clin Pharmacol 2007 Oct;21(5):555-8.

Girard P, Pansart Y, Coppe MC, Gillardin JM. Nefopam reduces thermal hypersensitivity in acute and postoperative pain models in the rat. Pharmacol Res 2001 Dec;44(6):541-5.

Girard P, Coppe MC, Verniers D, Pansart Y, Gillardin JM. Role of catecholamines and serotonin receptor subtypes in nefopam-induced antinociception. Pharmacol Res 2006 Sep;54(3):195-202.

Girard P, Pansart Y, Gillardin JM. Nefopam potentiates morphine antinociception in allodynia and hyperalgesia in the rat. Pharmacol Biochem Behav 2004 Apr;77(4):695-703.

Beloeil H, Delage N, Negre I, Mazoit JX, Benhamou D. The median effective dose of nefopam and morphine administered intravenously for postoperative pain after minor surgery: a prospective randomized double-blinded isobolographic study of their analgesic action. Anesth Analg 2004;98(2):395-400.

Kapfer B, Alfonsi P, Guignard B, Sessler DI, Chauvin M. Nefopam and ketamine comparably enhance postoperative analgesia. Anesth Analg 2005;100(1):169-74.

Biella GE, Groppetti A, Novelli A, Fernandez-Sanchez MT, Manfredi B, Sotgiu ML. Neuronal sensitization and its behavioral correlates in a rat model of neuropathy are prevented by a cyclic analog of orphenadrine. J Neurotrauma 2003;20(6):593-601.

Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983 Jun;16(2):109-10.

Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988 Apr;33(1):87-107.

Zhao C, Tall JM, Meyer RA, Raja SN. Antiallodynic effects of systemic and intrathecal morphine in the spared nerve injury model of neuropathic pain in rats. Anesthesiology 2004 Apr;100(4):905-11.

Stuesse SL, Crisp T, McBurney DL, Schechter JB, Lovell JA, Cruce WL. Neuropathic pain in aged rats: behavioral responses and astrocytic activation. Exp Brain Res 2001 Mar;137(2):219-27.

Choi Y, Yoon YW, Na HS, Kim SH, Chung JM. Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain 1994 Dec;59(3):369-76.

Vo T, Rice AS, Dworkin RH. Non-steroidal anti-inflammatory drugs for neuropathic pain: how do we explain continued widespread use? Pain 2009 Jun;143(3):169-71.

Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR, Bennett GJ, et al. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol 2003 Nov;60(11):1524-34.

Hamidi GA, Manaheji H, Janahmadi M, Noorbakhsh SM, Salami M. Co-administration of MK-801 and morphine attenuates neuropathic pain in rat. Physiol Behav 2006 Jul 30;88(4-5):628-35.

Dellemijn PL, van Duijn H, Vanneste JA. Prolonged treatment with transdermal fentanyl in neuropathic pain. J Pain Symptom Manage 1998 Oct;16(4):220-9.

Angst MS, Koppert W, Pahl I, Clark DJ, Schmelz M. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain 2003 Nov;106(1-2):49-57.

Singla A, Stojanovic MP, Chen L, Mao J. A differential diagnosis of hyperalgesia, toxicity, and withdrawal from intrathecalmorphine infusion. Anesth Analg 2007 Dec;105(6):1816-9.

Porreca F, Ossipov MH, Gebhart GF. Chronic pain and medullary descending facilitation. Trends Neurosci 2002 Jun;25(6):319-25.

Wiesenfeld-Hallin Z, Xu XJ, Hokfelt T. The role of spinal cholecystokinin in chronic pain states. Pharmacol Toxicol 2002 Dec;91(6):398-403.

Johnston IN, Milligan ED, Wieseler-Frank J, Frank MG, Zapata V, Campisi J, et al. A role for proinflammatory cytokines and fractalkine in analgesia, tolerance, and subsequent pain facilitation induced by chronic intrathecal morphine. J Neurosci 2004 Aug 18;24(33):7353-65.

Wilson NM, Jung H, Ripsch MS, Miller RJ, White FA. CXCR4 signaling mediates morphine-induced tactile hyperalgesia. Brain Behav Immun 2011 Mar;25(3):565-73.

Hutchinson MR, Coats BD, Lewis SS, Zhang Y, Sprunger DB, Rezvani N, et al. Proinflammatory cytokines oppose opioid-induced acute and chronic analgesia. Brain Behav Immun 2008 Nov;22(8):1178-89.

Erichsen HK, Hao JX, Xu XJ, Blackburn-Munro G. Comparative actions of the opioid analgesics morphine, methadone and codeine in rat models of peripheral and central neuropathic pain. Pain 2005 Aug;116(3):347-58.

Choi JI, Kim WM, Yoon MH, Lee HG. Antiallodynic Effect of Thalidomide and Morphine on Rat Spinal Nerve Ligation-induced Neuropathic Pain. Korean J Pain 2010 Sep;23(3):172-8.

Dellemijn P. Are opioids effective in relieving neuropathic pain? Pain 1999 Apr;80(3):453-62.

Kim J, Jung JI, Na HS, Hong SK, Yoon YW. Effects of morphine on mechanical allodynia in a rat model of central neuropathic pain. Neuroreport 2003 May 23;14(7):1017-20.

Gomaa AA, Aly SA, Badary MS, Ahmed EA. The immunopotentiator effects of nefopam. Int Immunopharmacol 2007 Feb;7(2):266-71.

Mimoz O, Incagnoli P, Josse C, Gillon MC, Kuhlman L, Mirand A, Soilleux H, Fletcher D. Analgesic efficacy and safety of nefopam vs. propacetamol following hepatic resection. Anaesthesia 2001 Jun;56(6):520-5.

Laboureyras E, Chateauraynaud J, Richebe P, Simonnet G. Long-term pain vulnerability after surgery in rats: prevention by nefopam, an analgesic with antihyperalgesic properties. Anesth Analg 2009 Aug;109(2):623-31.

Villier C, Mallaret MP. Nefopam abuse. Ann Pharmacother 2002 Oct;36(10):1564-6.




DOI: https://doi.org/10.22037/nbm.v1i1.4488