Cannabinoid receptors and pain

Activation of both cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors reduces nociceptive processing in acute and chronic animal models of pain. In addition, nociceptive processing is tonically modulated by endogenous cannabinoids (endocannabinoids, ECs). This review examines the role of cannabinoids and ECs in the brain stem–spinal pathway of pain inhibition. Preclinical studies evaluating cannabinoids in neuropathic pain management are also reviewed. Pharmacological tools modulating the interaction of cannabinoids with its receptors and the treatment of pain by the augmentation of EC levels, specifically anandamide, are discussed. Particular attention is attributed to neuropathic pain in which pharmacological manipulation resulting in EC accumulation can be protective and produce antinociception, thereby making the system an attractive therapeutic target. Finally, the therapeutic value of cannabinoids in clinical research is summarized. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.