DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20160078

A comparative study of the anti-nociceptive potential of duloxetine and carbamazepine in an animal model of neuropathic pain

Saurabh Kohli, Taruna Sharma, Juhi Kalra, Dilip C. Dhasmana

Abstract


Background: Pain is one of the most common symptoms encountered in clinical practice. Of the various types of pain, neuropathic pain represents one of the most difficult pain states to treat, with treatments being far from satisfactory. The drugs used are not fully effective and a drug that shows good efficacy in one neuropathic pain state may be ineffective in another. This study was done to compare the antinociceptive potential of duloxetine and carbamazepine, two drugs with different mechanisms of action in an animal model of neuropathic pain.

Methods: Antinociceptive effect of duloxetine (15 mg/kg intraperitoneally) and carbamazepine (20 mg/kg intraperitoneally) was evaluated in the sciatic chronic constriction injury (CCI) model of neuropathic pain in rats. Thermal hyperalgesia, evaluated by the hot plate method; and mechanical hyperalgesia, evaluated by the pinprick method were used as measures of neuropathic pain.

Results: A significant degree of thermal and mechanical hyperalgesia (p ≤0.05) was produced in both the drug groups. Both drugs produced a significant decrease in thermal and mechanical hyperalgesia throughout the study period (p ≤0.01 for both drugs). In comparison to duloxetine, carbamazepine was less efficacious (p ≤0.05 at 30, 60 minutes; p ≤0.01 at 120 minutes) for thermal hyperalgesia as well as for mechanical hyperalgesia (p ≤0.05 at 30, 60 minutes; p≤0.01 at 120 minutes). Only duloxetine was able to almost completely reverse both thermal & mechanical hyperalgesia to near pre-neuropathy levels.

Conclusions: Duloxetine showed better antinociceptive potential as compared to carbamazepine as reflected by a more complete reduction in thermal & mechanical hyperalgesia in the sciatic CCI model of neuropathic pain.


Keywords


Neuropathic pain, Duloxetine, Carbamazepine, Antinociceptive

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References


Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70:1630-5.

Knotova H, Pappagallo M. Adjuvant analgesics. Med Clin N Am. 2007;91:113-24

Bridges D, Thompson SWN, Rice ASC. Mechanisms of neuropathic pain. Br J Anaesth. 2001;87(1):12-26.

Saxena AS, Azad R. Advances in the mechanisms, diagnosis and management of neuropathic pain: current opinions and future perspectives. Indian J Anaesth. 2006;50(4):249-57.

Colleoni M, Sacerdote P. Murine models of human neuropathic pain. Biochimica et Biophysica Acta. 2010;1802(10):924-33

Iyenger S, Amy A, Webster AA, Hamrick-Luieke SK, Xu JY, Simmons RMA. Efficacy of duloxetine, a potent balanced serotonin-norepinephrine reuptake inhibitor in persistent pain models in rats. J Pharmacol Exp Ther. 2004;311:576-84.

Gordon BM, Nete I, Helle E. A comparison of the antinociceptive effects of voltage activated sodium channel blockers in the formalin test. Eur J Pharmacol. 2002;445(3):231-8.

Todorovic SM, Rastogi AJ, Todorovic VJ. Potent analgesic effects of anticonvulsants on peripheral thermal nociception in rats.Br J Pharmacol. 2003;140:255-60.

Liu L, Zheng T, Morris MJ, Wallengren C, Clarke AL, Reid CA et al. The mechanism of carbamazepine aggravation of absence seizures. J Pharmacol Exp Ther. 2000;319:790-8.

Vogel GH, Vogel WGH, editors, Drug discovery and evaluation- pharmacological assays. 2nd ed. New York: Verlog Springer publication, 1996.

Gonzalez MI, Field MJ, Hughes J, Singh L. Evaluation of the selective NK1 receptor antagonist CI-1021 in animal models of inflammatory and neuropathic pain. J Pharmacol Exp Ther. 2000;294(2):444-50.

Wang YX, Bowersox SS, Pettus M, Gao DA. Antinociceptive properties of fenfluramine, a serotonin reuptake inhibitor, in a rat model of neuropathy. J Pharmacol Exp Ther. 1999;291:1008-16.

Moulin DE, Boulanger A, Clark AJ, Clarke H, Dao T, Finley GA et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014;19(6):328-35.

Bomholt SF, Mikkelsen JP, Blackburn-Munro G. Antinociceptive effects of the antidepressants amitriptyline, duloxetine, mirtazapine and citalopram in animal models of acute, persistent and neuropathic pain. Neuropharmacology. 2005;48(2):252-63.

Golan DE, Tashjian AH, Armstrong EJ, editors. Principles of pharmacology- the pathophysiologic basis of drug therapy. 2nd ed. New Delhi: Wolters Kluver(India) Pvt. Ltd, 2008.

Demant DT, Lund K, Vollert J, Maier C, Segerdahl M, Finnerup NB et al. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomized, double-blind, placebo controlled phenotype stratified study. Pain. 2014;155(11):2263­73.

Chogtu B, Bairy KL, Himabindu P, Dhar S. Comparing the efficacy of carbamazepine, gabapentin and lamotrigine in chronic constriction injury model of neuropathic pain in rats. Int J Nutr Pharmacol Neurol Dis. 2013;3(1):34-8.

De Vry J, Kuhl E, Franken-Kunkel P, Eckel G. Pharmacological characterization of the chronic constriction injury model of neuropathic pain. Eur J Pharmacol. 2004;491(2-3):137-48.