Evidence that CB-1 and CB-2 cannabinoid receptors mediate antinociception in neuropathic pain in the rat

The roles of the two cannabinoid receptor subtypes, CB-1 and CB-2, have not been clarified in cannabinoid-mediated analgesia. We investigated the efficacy of the non-selective cannabinoid receptor agonist CP55,940 in the modulation of responses in the rat to both acute pain (tail flick) and neuropathic pain (tactile allodynia following chronic L5/6 spinal nerve ligation). Responses were also assessed in the presence of the CB-1 antagonist SR141716A (SR1) and the CB-2 antagonist SR144528 (SR2). CP55,940 attenuated tactile allodynia (ED50 0.04 mg/kg i.t. (95% CI 0.032-0.044 mg/ka). 0.12 mg/kg i.p. (95% CI 0.10-0.15 mg/kg)) and induced thermal antinociception (ED50 tail flick 0.07 mg/kg i.t. (95% CI 0.05-0.10 mg/kg), 0.17 mg/kg i.p. (95% CI 0.11-0.26 mg/kg)). SRI 0.5 mg/kg i.t. attenuated the antinociceptive effect of CP55,940 in both modalities. However, SRI 1.0 mg/kg i.p. decreased tail flick latency but had no effect on tactile allodynia antinocicepti on. In contrast, SR21.0 mg/kg i.p. significantly decreased the effect of i.p. CP55,940 on both tail flick antinociception and tactile allodynia (P < 0.05). The combination of SR1 and SR2 (i.p.) had an additive effect in decreasing the antinociception induced by CP55,940 on tail flick responses (P < 0.005). These results suggest a role for CB-2 receptor-mediated antinociception in both acute and neuropathic pain in addition to centrally located CB-1 mechanisms. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.