2-Arachidonoylglycerol-mediated endocannabinoid signaling modulates mechanical hypersensitivity associated with alcohol withdrawal in mice.

Our findings demonstrate the critical role of 2-AG signaling in the bidirectional regulation of mechanical sensitivity during alcohol withdrawal, with enhancement of 2-AG levels reducing sensitivity, and inhibition of 2-AG signaling exacerbating sensitivity. These data suggest that 2-AG augmentation represents a novel approach to the treatment of alcohol withdrawal-associated hyperalgesia and AUD in patients with comorbid pain disorders.