The antinociceptive effect of Δ9-tetrahydrocannabinol in the arthritic rat involves the CB 2 cannabinoid receptor

Abstract

Cannabinoid CB 2 receptors have been implicated in antinociception in animal models of both acute and chronic pain. We evaluated the role both cannabinoid CB 1 and CB 2 receptors in mechanonociception in non-arthritic and arthritic rats. The antinociceptive effect of Δ 9-tetrahydrocannabinol (Δ 9THC) was determined in rats following administration of the cannabinoid CB 1 receptor-selective antagonist, SR141716A, the cannabinoid CB 2 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 1 h prior to Δ 9THC (4mg/kg; i.p) or 1:1:18 vehicle and antinociception determined 30min post Δ 9THC. AD 50's for both antagonists were calculated with 95% confidence limits. In addition, midbrain and spinal cord were removed for determination of cannabinoid CB 1 and CB 2 receptor protein density in the rats. SR144528 significantly attenuated the antinociceptive effect of Δ 9THC 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 Δ 9THC-induced antinociception in both the non-arthritic [AD 50 = 1.4 (0.8–2) mg/kg] and arthritic rat [AD 50 = 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 CB 2 receptor plays a critical role in cannabinoid-mediated antinociception, particularly in models of chronic inflammatory pain.