Cannabinoid CB2 Receptor-Mediated Anti-nociception in Models of Acute and Chronic Pain

The endocannabinoid system consists of cannabinoid CB₁ and CB₂ receptors, endogenous ligands and their synthesising/metabolising enzymes. Cannabinoid receptors are present at key sites involved in the relay and modulation of nociceptive information. The analgesic effects of cannabinoids have been well documented. The usefulness of nonselective cannabinoid agonists can, however, be limited by psychoactive side effects associated with activation of CB₁ receptors. Following the recent evidence for CB₂ receptors existing in the nervous system and reports of their up-regulation in chronic pain states and neurodegenerative diseases, much research is now aimed at shedding light on the role of the CB₂ receptor in human disease. Recent studies have demonstrated anti-nociceptive effects of selective CB₂ receptor agonists in animal models of pain in the absence of CNS side effects. This review focuses on the analgesic potential of CB₂ receptor agonists for inflammatory, post-operative and neuropathic pain states and discusses their possible sites and mechanisms of action. Jhaveri and Sagar joint first author.