Sex and pain modality differentially modulate alcohol consumption in mice.

Abstract

INTRODUCTION: Population-based studies show that chronic pain is associated with increased alcohol use and reduced pain, increasing the risk of hazardous drinking and developing alcohol use disorders (AUD). Preclinical models allow investigation of the mechanisms linking pain and alcohol use. METHODS: This study used mouse models to examine how chronic pain alters alcohol intake. We measured the time course and magnitude of ethanol intake and preference after Complete Freund's Adjuvant (CFA)- or paclitaxel-induced chronic pain using the two-bottle choice paradigm and assessed whether ethanol intake altered CFA-induced mechanical sensitivity. RESULTS: CFA administration increased ethanol intake and preference in male but not female mice. This effect was blocked by the selective kappa antagonist nor-binaltorphimine dihydrochloride (nor-BNI). Fourteen days of ethanol exposure partially attenuated CFA-induced mechanical hypersensitivity in males. By contrast, paclitaxel reduced ethanol intake and preference in males without affecting females in the two-bottle choice paradigm. CONCLUSION: Taken together, our findings emphasize the complex, sex- and model-dependent relationship between chronic pain and alcohol consumption.