Cannabinoid CB1 receptor inhibition of mechanically evoked responses of spinal neurones in control rats, but not in rats with hindpaw inflammation.

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 microM) 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 microM) attenuated the inhibitory effects of ACEA (27 microM). 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.