Cannabinoid CB 1 receptor inhibition of mechanically evoked responses of spinal neurones in control rats, but not in rats with hindpaw inflammation

Abstract

Spinally administered cannabinoid receptor agonists are anti-nociceptive in a variety of models of acute and persistent pain. The present study investigated the effects of activation of spinal cannabinoid CB 1 receptors on mechanically evoked responses of spinal neurones in acute and inflammatory pain states. In vivo electrophysiology studies were carried out in anaesthetised rats. Effects of spinal administration of a selective cannabinoid CB 1 receptor agonist, arachidonyl-2-chloroethylamide (ACEA), on mechanically evoked responses of dorsal horn neurones in control rats and rats with peripheral hindpaw carrageenan-induced inflammation were compared. ACEA (0.27 nM–27 μM) significantly inhibited innocuous and noxious mechanically evoked responses of dorsal horn neurones in control rats. Pre-administration of the CB 1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1(2,4-dichlorophenyl)-4-methyl-1- H-pyrazole-3-carboxyamide, SR141716A, (0.43 μM) attenuated the inhibitory effects of ACEA (27 μM). ACEA did not alter mechanically evoked responses of dorsal horn neurones in rats with hindpaw carrageenan-induced inflammation. Following peripheral inflammation, there is a loss of spinal CB 1 receptor-mediated inhibition of mechanically evoked responses, which is suggestive of a functional down-regulation of CB 1 receptors under these conditions.