Cannabinoid CB2receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain

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Abstract
Cannabinoids suppress behavioural responses to noxious stimulation and suppress nociceptive transmission through activation of CB1and CB2receptor subtypes. CB1receptors are expressed at high levels in the central nervous system (CNS), whereas CB2receptors are found predominantly, but not exclusively, outside the CNS. CB2receptors 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 CB2receptors as a therapeutic target for treating pathological pain states with limited centrally, mediated side effects. The development of CB2‐selective agonists (with minimal affinity for CB1) as well as mutant mice lacking CB2receptors has provided pharmacological and genetic tools required to evaluate the effectiveness of CB2agonists in suppressing persistent pain states. This review will examine the efficacy of cannabinoid CB2‐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 CB2‐selective agonists in behavioural studies and neural mechanisms of pain suppression. Finally, the therapeutic potential and possible limitations of CB2‐based pharmacotherapies for pathological pain states induced by tissue and nerve injury are discussed.British Journal of Pharmacology(2008)153, 319–334; doi:10.1038/sj.bjp.0707531; published online 12 November 2007

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