Endocannabinoid mechanisms of pain modulation.

Cannabinoids are antinociceptive in animal models of acute, tissue injury-, and nerve injury-induced nociception. This review examines the biology of endogenous cannabinoids (endocannabinoids) and behavioral, neurophysiological, and neuroanatomical evidence supporting the notion that cannabinoids play a role in pain modulation. Behavioral pharmacological approaches, in conjunction with the identification and quantification of endocannabinoids through the use of liquid and gas chromatography mass spectrometry, have provided insight into the functional roles of endocannabinoids in pain modulation. Here we examine the distribution of cannabinoid receptors and endocannabinoid-hydrolyzing enzymes within pain modulatory circuits together with behavioral, neurochemical, and neurophysiological studies that suggest a role for endocannabinoid signaling in pain modulation. This review will provide a comprehensive evaluation of the roles of the endocannabinoids 2-arachidonoylglycerol and anandamide in stress-induced analgesia. These findings provide a functional framework with which to understand the roles of endocannabinoids in nociceptive processing at the supraspinal level.