An endocannabinoid mechanism for stress-induced analgesia

Article

关键词: STIMULUS-EVOKED ACTIVITY;    DORSAL-HORN;    NEURONS;    BRAIN;    SUPPRESSION;    INHIBITORS;    RECEPTORS;    LIPASE;    ESTERS;    FORMS;   

DOI  :  10.1038/nature03658

来源: SCIE

【 摘 要 】

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(1), is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB1 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) (2-AG) and anandamide(3). A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase(4,5), 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(6), 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.

【 授权许可】

Free