Cannabinoid (CB) receptor agonists alleviate neuropathic hyperalgesia and allodynia but also have undesirable psychoactive effects. An alternative strategy is inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), the principal enzymes responsible for the degradation of the respective endogenous cannabinoids, anandamide and 2-arachydonylglycerol. Recent results suggest that FAAH and/or MAGL inhibition reduces nociception with minimal behavioral effects. In this issue, Kinsey et al., aim to clarify the role of cannabinoid receptors as mediators of antiallodynic effects of FAAH and MAGL inhibitors in the chronic constriction injury mouse model. The study used two reported FAAH inhibitors and a novel MAGL inhibitor. In the current study, the authors demonstrate that both CB1 and CB2 receptors mediate the antiallodynic responses of FAAH inhibitors, whereas only the CB2 receptor is involved in the antiallodynic effects of an MAGL inhibitor. The study also rules out involvement of opioid receptors in mediating the antiallodynic effects of FAAH inhibitors. The authors conclude that inhibition of FAAH and MAGL reduces neuropathic pain via distinct mechanisms that define viable targets for the development of analgesic therapeutics.
See article at J Pharmacol Exp Ther 2009, 330:902–910.
- The American Society for Pharmacology and Experimental Therapeutics