Within and Beyond the Binary: Sex and Gender Differences in Pain and Alcohol Use Disorder

Alcohol use disorder (AUD) and chronic pain are frequently comorbid conditions. This review aims to communicate recent research describing the bidirectional effects of pain experience and alcohol use, while focusing on sex and gender differences at this intersection with an emphasis on translational research. Most pain syndromes affect people assigned female at birth (AFAB). Although people assigned male at birth (AMAB) typically drink more than AFABs, AFABs progress to AUD more quickly and experience more alcohol-related comorbidities. In the preclinical setting, different alcohol models highlight sex differences in the escalation of alcohol drinking, while a state of alcohol dependence appears to produce sex-specific alterations in withdrawal-induced pain- and anxiety-like behaviors. Preclinical and clinical studies are accelerating in order to elucidate important sex differences in both chronic pain and AUD. A better understanding of the physiological mechanisms underlying pain and AUD will support the discovery of more effective, potentially sex-specific, therapeutic options for these devastating co-morbid conditions.