The cannabinoid CB1 receptor antagonist, SR141716A, selectively facilitates nociceptive responses of dorsal horn neurones in the rat

The effect of spinal administration of the selective cannabinoid CB1 recept or antagonist, SR141716A, and the selective CB2 receptor antagonist, SR1445 28, on innocuous versus noxious evoked responses of dorsal horn neurones in the spinal cord of the anaesthetized rat was investigated. SR141716A (0.00 1-l ng 50 mu 1(-1)) dose-relatedly facilitated the non-potentiated componen t of the electrical C-fibre mediated neuronal response (120 +/- 6, 156 +/- 13, 192 +/- 33 and 192 +/- 31% of control respectively; n=6). In contrast, SR144528 (0.001-1 ng 50 mu 1(-1)) did not influence the non-potentiated com ponent of the C-fibre evoked neuronal response (n=5). The electrical evoked A beta-fibre mediated neuronal responses were not influenced by SR141716A or SR144528. The results of this study provide evidence that tonic cannabin oid CB1 receptor activation, but not CB2 receptor activation, attenuates ac ute nociceptive transmission, at the level of the spinal cord. These result s suggest a selective antinociceptive role of the endogenous cannabinoids a t spinal CB1 receptors.