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

ABSTRACT

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