Cannabinoid CB2 receptors have been implicated in antinociception in animal models of both acute and chronic pain. We evaluated the role both cannabinoid CB1 and CB2 receptors in mechanonociception in non-arthritic and arthritic rats. The antinociceptive effect of Delta(9)-tetrahydrocannabinol (Delta(THC)-T-9) was determined in rats following administration of the cannabinoid CB1 receptor-selective antagonist, SR141716A, the cannabinoid CB2 receptor-selective antagonist, SR144528, or vehicle. Male Sprague-Dawley rats were rendered arthritic using Freund's complete adjuvant and tested for mechanical hyperalgesia in the paw-pressure test. Arthritic rats had a baseline paw-pressure of 83 3.6g versus a paw-pressure of 177 +/- 6.42g in non-arthritic rats. SR144528 or SR141716A (various doses mg/kg; i.p.) or 1:1: 18 (ethanol: emulphor: saline) vehicle were injected I h prior to Delta(THC)-T-9 (4mg/kg; i.p) or 1: 1: 18 vehicle and antinociception determined 30min post Delta(THC)-T-9. AD50'S for both antagonists were calculated with 95% confidence limits. In addition, midbrain and spinal cord were removed for determination of cannabinoid CB1 and CB2 receptor protein density in the rats. SR144528 significantly attenuated the antinociceptive effect of Delta(THC)-T-9 in the arthritic rats [AD(50) = 3.3 (2.7-4) mg/kg], but not in the non-arthritic rats at a dose of 10/mg/kg. SR141716A significantly attenuated Delta(THC)-T-9-induced antinociception in both the non-arthritic [AD50 = 1.4 (0.9-2) mg/kg] and arthritic rat [AD50 = 2.6 (1.8-3.1) mg/kg]. SR141716A or SR144528 alone did not result in a hyperalgesic effect as compared to vehicle. Our results indicate that the cannabinoid CB2 receptor plays a critical role in cannabinoid-mediated antinociception, particularly in models of chronic inflammatory pain. Published by Elsevier B.V.
