AbstractBackground and purpose:
2-arachidonoyl glycerol (2-AG) is an endogenous cannabinoid with central antinociceptive properties. Its degradation is catalysed by monoacylglycerol lipase (MGL) whose activity is inhibited by URB602, a new synthetic compound. The peripheral antinociceptive effects of 2-AG and URB602 in an inflammatory model of pain are not yet determined. We have evaluated these effects with and without the cannabinoid CB1 (AM251) and CB2 (AM630) receptor antagonists.Experimental approach:
Inflammation was induced in rat hind paws by intraplantar injection of formalin. Nociception was assessed behaviourally over the next 60 min, in 19 experimental groups: (1) control; (2–6) 2-AG (0.01–100 μg); (7) AM251 (80 μg); (8) AM251+2-AG (10 μg); (9) AM630 (25 μg); (10) AM630+2-AG (10 μg); (11–16) URB602 (0.1–500 μg); (17) 2-AG+URB602 (ED50); (18) AM251+URB602 (ED50); (19) AM630+URB602 (ED50). Drugs were injected s.c. in the dorsal surface of the hind paw (50 μl), 15 min before formalin injection into the same paw.Key results:
2-AG and URB602 produced dose-dependent antinociceptive effects for the late phases of the formalin test with ED50 of 0.65±0.455 μg and 68±14.3 μg, respectively. Their combination at ED50 doses produced an additive antinociceptive effect. These effects were inhibited by AM630 but not by AM251 for 2-AG and by the two cannabinoid antagonists for URB602.Conclusions and implications:
Locally injected 2-AG and URB602 decreased pain behaviour in a dose-dependent manner in an inflammatory model of pain. The antinociceptive effect of 2-AG was mediated by the CB2 receptor.