An endocannabinoid mechanism for stress-induced analgesia - PubMed (original) (raw)

. 2005 Jun 23;435(7045):1108-12.

doi: 10.1038/nature03658.

Richard L Suplita, Nathan M Bolton, Mark H Neely, Darren Fegley, Regina Mangieri, Jocelyn F Krey, J Michael Walker, Philip V Holmes, Jonathon D Crystal, Andrea Duranti, Andrea Tontini, Marco Mor, Giorgio Tarzia, Daniele Piomelli

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An endocannabinoid mechanism for stress-induced analgesia

Andrea G Hohmann et al. Nature. 2005.

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Abstract

Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB(1) receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol (2-AG) and anandamide. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target.

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