Spinal and peripheral mechanisms of cannabinoid antinociception: behavioral, neurophysiological and neuroanatomical perspectives.

A large body of literature indicates that cannabinoids suppress behavioral responses to acute and persistent noxious stimulation. This review examines behavioral, neurophysiological and neuroanatomical evidence supporting a role for cannabinoids in suppressing nociceptive transmission at spinal and peripheral levels. The development of subtype-selective competitive antagonists and high-affinity agonists provides the pharmacological tools required to study cannabinoid antinociceptive mechanisms. These studies provide insight into the functional roles of cannabinoid receptor subtypes, CB1 and CB2, in cannabinoid antinociceptive mechanisms as revealed in animal models of acute and persistent (somatic inflammatory, visceral inflammatory, neuropathic) pain. Localization studies employing receptor binding and quantitative autoradiography, immunocytochemistry and in situ hybridization are reviewed to examine the distribution of cannabinoid receptors at these levels and provide a neuroanatomical framework with which to understand the roles of endogenous cannabinoids in sensory processing.