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Evaluation of Lercanidipine in Paclitaxel-Induced Neuropathic Pain Model in Rat: A Preliminary Study

DOI: 10.1155/2012/143579

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Objective. To demonstrate the antinociceptive effect of lercanidipine in paclitaxel-induced neuropathy model in rat. Materials and Methods. A total of 30 rats were divided into five groups of six rats in each group as follows: Gr I: 0.9% NaCl, Gr II: paclitaxel?+?0.9% NaCl, Gr III: paclitaxel?+?lercanidipine 0.5?μg/kg, Gr IV: paclitaxel?+?lercanidipine 1?μg/kg, and Gr V: paclitaxel?+?lercanidipine 2.5?μg/kg. Paclitaxel-induced neuropathic pain in rat was produced by single intraperitoneal (i.p.) injection of 1?mg/kg of paclitaxel on four alternate days (0, 2, 4, and 6). The tail flick and cold allodynia methods were used for assessing the pain threshold, and the assessments were done on days 0 (before first dose of paclitaxel) and on days 7, 14, 21, and 28. Results. There was a significant decrease ( ) in the tail flick and cold allodynia latency in the paclitaxel-alone group from day 14 onward when compared with day 0. In the lercanidipine groups, the decrease in the tail flick and cold allodynia latency was not observed in 1.0 and 2.5?μg/kg groups and it was statistically significant ( ) when compared with paclitaxel-alone group. 1. Introduction Neuropathic pain is a type of pain which is caused by damage to or dysfunction of the nervous system. [1] Neuropathic pain cannot be explained by a single disease process or a single specific location of damage. It is a disorder in the structure and function of peripheral, motor, sensory, and/or autonomic neurons either partially or completely [2]. Neuropathic pain may be divided into peripheral, central, or mixed (peripheral and central) neuropathic pain. As much as 7% to 8% of the population is affected and in 5%, it may be severe [3]. In order to evaluate the mechanisms of neuropathic pain and to find new therapeutic approaches, different experimental neuropathic pain models have been developed which include chronic constriction injury of sciatic nerve, partial sciatic nerve ligation, and partial transaction of sciatic nerve. Current knowledge regarding the mechanisms of neuropathic pain is incomplete and is biased by a focus on animal models of peripheral nerve injury, and the treatment is often unsatisfactory. It is an area of largely unmet therapeutic need. The current pharmacological mainstays of clinical management are tricyclic antidepressants and certain anticonvulsants, but these only achieve clinically significant (>50%) pain relief in 40–60% of patients and are associated with several side effects. Opioids are generally considered to be less effective in neuropathic pain than in inflammatory pain


[1]  K. M. Foley, “Opioids and chronic neuropathic pain,” New England Journal of Medicine, vol. 348, no. 13, pp. 1279–1281, 2003.
[2]  P. Hansson, “Neuropathic pain: clinical characteristics and diagnostic workup,” European Journal of Pain, vol. 6, no. 1, pp. 47–50, 2002.
[3]  D. Bouhassira, M. Lantéri-Minet, N. Attal, B. Laurent, and C. Touboul, “Prevalence of chronic pain with neuropathic characteristics in the general population,” Pain, vol. 136, no. 3, pp. 380–387, 2008.
[4]  R. H. Dworkin, A. B. O'Connor, M. Backonja et al., “Pharmacologic management of neuropathic pain: evidence-based recommendations,” Pain, vol. 132, no. 3, pp. 237–251, 2007.
[5]  R. C. Polomano, A. J. Mannes, U. S. Clark, and G. J. Bennett, “A painful peripheral neuropathy in the rat produced by the chemotherapeutic drug, paclitaxel,” Pain, vol. 94, no. 3, pp. 293–304, 2001.
[6]  E. A. Matthews and A. H. Dickenson, “Effects of ethosuximide, a T-type Ca+2 channel blocker, on dorsal horn neuronal responses in rats,” European Journal of Pharmacology, vol. 25, pp. 2561–2569, 2007.
[7]  W. L. D'Armour and D. L. Smith, “Method of determining loss of pain sensation,” Journal of Pharmacology and Experimental Therapeutics, vol. 72, pp. 74–90, 1941.
[8]  H. S. Na, J. S. Han, K. H. Ko, and S. K. Hong, “A behavioral model for peripheral neuropathy produced in rat's tail by inferior caudal trunk injury,” Neuroscience Letters, vol. 177, no. 1-2, pp. 50–52, 1994.
[9]  P. Dellemijn, “Are opioids effective in relieving neuropathic pain?” Pain, vol. 80, no. 3, pp. 453–462, 1999.
[10]  C. D. Scripture, W. D. Figg, and A. Sparreboom, “Peripheral neuropathy induced by paclitaxel: recent insights and future perspectives,” Current Neuropharmacology, vol. 4, no. 2, pp. 165–172, 2006.
[11]  E. A. Matthews and A. H. Dickenson, “Effects of ethosuximide, a T-type Ca2+ channel blocker, on dorsal horn neuronal responses in rats,” European Journal of Pharmacology, vol. 415, no. 2-3, pp. 141–149, 2001.
[12]  E. A. Matthews and A. H. Dickenson, “Effects of spinally delivered N- and P-type voltage-dependent calcium channel antagonists on dorsal horn neuronal responses in a rat model of neuropathy,” Pain, vol. 92, no. 1-2, pp. 235–246, 2001.
[13]  E. A. Matthews, L. A. Bee, G. J. Stephens, and A. H. Dickenson, “The Cav2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain,” European Journal of Neuroscience, vol. 25, no. 12, pp. 3561–3569, 2007.
[14]  R. Suzuki, W. Rahman, L. J. Rygh, M. Webber, S. P. Hunt, and A. H. Dickenson, “Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin,” Pain, vol. 117, no. 3, pp. 292–303, 2005.
[15]  D. Hota, R. Joshi, A. Srinivasan, and A. Chakraborti, Effect of lercanidipine in formalin induced facial pain model in rat, Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, unpublished data.
[16]  K. Okubo, T. Takahashi, F. Sekiguchi et al., “Inhibition of T-type calcium channels and hydrogen sulfide-forming enzyme reverses paclitaxel-evoked neuropathic hyperalgesia in rats,” Neuroscience, vol. 188, pp. 148–156, 2011.
[17]  S. M. Todorovic and V. Jevtovic-Todorovic, “T-type voltage-gated calcium channels as targets for the development of novel pain therapies,” British Journal of Pharmacology, vol. 163, no. 3, pp. 484–495, 2011.
[18]  S. J. L. Flatters and G. J. Bennett, “Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy,” Pain, vol. 109, no. 1-2, pp. 150–161, 2004.
[19]  T. Kawashiri, N. Egashira, Y. Itoh et al., “Neurotropin reverses paclitaxel-induced neuropathy without affecting anti-tumour efficacy,” European Journal of Cancer, vol. 45, no. 1, pp. 154–163, 2009.
[20]  V. Chentanez, S. Sanguanrungsirigul, and N. Panyasawad, “Effects of ganglioside on paclitaxel (Taxol) induced neuropathy in rats,” Journal of the Medical Association of Thailand, vol. 86, no. 5, pp. 449–456, 2003.
[21]  V. Chentanez, N. Thanomsridejchai, N. Duangmardphon et al., “Ganglioside GM1 (porcine) ameliorates paclitaxel-induced neuropathy in rats,” Journal of the Medical Association of Thailand, vol. 92, no. 1, pp. 50–57, 2009.
[22]  S. J. L. Flatters, W. H. Xiao, and G. J. Bennett, “Acetyl-L-carnitine prevents and reduces paclitaxel-induced painful peripheral neuropathy,” Neuroscience Letters, vol. 397, no. 3, pp. 219–223, 2006.


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