Evolutionism

¹Department of Psychology, Neuroscience and Behavior Program, University of Georgia, Athens, GA, USA

Correspondence: Dr AG Hohmann, Department of Psychology, Neuroscience and Behavior Program, University of Georgia, Athens, GA 30602-3013, USA. E-mail: ahohmann@uga.edu

Received 24 July 2007; Revised 24 September 2007; Accepted 4 October 2007; Published online 12 November 2007.

Abstract

Cannabinoids suppress behavioural responses to noxious stimulation and suppress nociceptive transmission through activation of CB₁ and CB₂receptor subtypes. CB₁ receptors are expressed at high levels in the central nervous system (CNS), whereas CB₂ receptors are found predominantly, but not exclusively, outside the CNS. CB₂ 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 CB₂ receptors 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 CB₂ receptors has provided pharmacological and genetic tools required to evaluate the effectiveness of CB₂ agonists 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.