Cannabinoid CB 2 receptors: A therapeutic target for the treatment of inflammatory and neuropathic pain

Abstract

Cannabinoids suppress behavioural responses to noxious stimulation and suppress nociceptive transmission through activation of CB 1 and CB 2 receptor subtypes. CB 1 receptors are expressed at high levels in the central nervous system (CNS), whereas CB 2 receptors are found predominantly, but not exclusively, outside the CNS. CB 2 receptors are also upregulated in the CNS and dorsal root ganglia by pathological pain states. Here, we review behavioural, neurochemical and electrophysiological data, which identify cannabinoid CB 2 receptors as a therapeutic target for treating pathological pain states with limited centrally, mediated side effects. The development of CB 2-selective agonists (with minimal affinity for CB 1) as well as mutant mice lacking CB 2 receptors has provided pharmacological and genetic tools required to evaluate the effectiveness of CB 2 agonists in suppressing persistent pain states. This review will examine the efficacy of cannabinoid CB 2-selective agonists in suppressing acute, inflammatory and neuropathic nociception following systemic and local routes of administration. Data derived from behavioural, neurochemical and neurophysiological approaches are discussed to better understand the relationship between antinociceptive effects induced by CB 2-selective agonists in behavioural studies and neural mechanisms of pain suppression. Finally, the therapeutic potential and possible limitations of CB 2-based pharmacotherapies for pathological pain states induced by tissue and nerve injury are discussed. © 2008 Nature Publishing Group All rights reserved.