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 receptor antagonist, SR141716A, and the selective CB2 receptor antagonist, SR144528, on innocuous versus noxious evoked responses of dorsal horn neurones in the spinal cord of the anaesthetized rat was investigated. SR141716A (0.001-1 ng 50 microl(-1)) dose-relatedly facilitated the non-potentiated component 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 microl(-1)) did not influence the non-potentiated component of the C-fibre evoked neuronal response (n=5). The electrical evoked Abeta-fibre mediated neuronal responses were not influenced by SR141716A or SR144528. The results of this study provide evidence that tonic cannabinoid CB1 receptor activation, but not CB2 receptor activation, attenuates acute nociceptive transmission, at the level of the spinal cord. These results suggest a selective antinociceptive role of the endogenous cannabinoids at spinal CB1 receptors.