Targeting the endocannabinoid-eicosanoid axis to treat pain: Promise and pitfalls.

In this issue of Cell Chemical Biology, Tufail et al.1 demonstrate that the peripheral diacylglycerol lipase α/β inhibitor A1480LS exerts potent anti-inflammatory and analgesic effects by blocking 2-arachidonoylglycerol synthesis and reducing arachidonate-derived eicosanoid production. However, potential risks from altered protein kinase C signaling due to elevated diacylglycerols warrant further evaluation in future therapeutic applications.