Capsazepine, a Transient Receptor Potential Vanilloid Type 1 (TRPV1) Antagonist, Attenuates Antinociceptive Effect of CB1 Receptor agonist, WIN55,212-2, in the Rat Nucleus Cuneiformis

* Corresponding Author: Abbas Haghparast, Msc, PhD Associate Professor of Neurophysiology, Single Unit Recording Laboratory, Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Evin St., Shahid Chamran Exp.way. P.O.Box: 19615-1178, Tehran, IRAN Tel/Fax: +98 21 2243 1624. Mobile: +98 912 214 9857 E-mail: Dr. [email protected]. Website: http://www.nrciran.com/ Introduction: Nucleus cuneiformis (NCF), as part of descending pain inhibitory system, cooperates with periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) in supraspinal modulation of pain. Cannabinoids have analgesic effects in the PAG, RVM and NCF. The transient receptor potential vanilloid type 1(TRPV1) can be activated by anandamide and WIN55,212-2 as a cannabinoid receptor agonist. The aim of the current study is to investigate the possible interplay between the cannabinoid and vanilloid systems for modulation of pain at the NCF. Methods: In this study, a cannabinoid receptor agonist, WIN55,212-2 ( 15 μg/0.3 μl DMSO), and selective TRPV1 receptor antagonist, capsazepine (10, 25, 50 and100 nmol/0.3 μl DMSO), were microinjected bilaterally into the NCF, and tailflick and formalin tests were used to assess the animal’s pain-related behaviors at 5-min intervals for a 60-min period. Results: Our findings demonstrated that analgesic effect of WIN55,212-2 were dose-dependently attenuated by capsazepine in both tests. In the tail-flick test, capsazepine at both doses of 50 (P<0.01) and 100 (P<0.001) nmol could significantly prevent the antinociceptive effect of WIN55,212-2 while capsazepine, in formalin test, could decreased its antinociceptive effect at the dose of 50 nmol (P<0.05) as well. On the other hand, solely administration of the highest dose of capsazepine in both tests did not alter the pain-related behaviors. Discussion: It suggests a possible role for TRPV1 receptors in NCF-mediated cannabinoid-induced antinociception. A B S T R A C T Article info: Received: 10 April 2011 First Revision: 22 April 2011 Accepted: 12 May 2011