Mitochondrial dysfunction at the intersection of alcohol use disorder and chronic pain

Alcohol use for pain relief dates back centuries. This profound analgesic efficacy also represents a strong motivational force that drives excessive drinking, fostering the development and severity of alcohol use disorder (AUD) in vulnerable individuals. Paradoxically, excessive alcohol drinking contributes to a multifactorial neuropathy, increasing nociceptive sensitivity (termed hyperalgesia) and pain-related negative affect, which may promote further alcohol use to manage either preexisting or newly emerging pain symptoms via stress-related neural damage and potentiation of negative reinforcement behavioral systems. These close relationships reflect the urgent need for better research conceptualizations and translational successes for the treatment of both chronic pain and addiction-related disorders. Mitochondrial health is particularly important across critical networks of neurons and nociceptive fibers, where continuous bioenergetic supply is required for axonal transport, repair, and synaptic transmission. Specific bioenergetic mechanisms underlying peripheral nerve damage and subsequent central nervous system adaptations in functional association with pain and excessive alcohol drinking are starting to be discovered. This focused review proposes that mitochondrial damage may unify several convergent pathophysiological mechanisms known to manifest in the context of both chronic pain and AUD and to be particularly relevant for vulnerable patient populations such as persons living with human immunodeficiency virus (HIV). Future research directions aimed at developing and testing novel therapeutic avenues to support mitochondrial health may provide safer and more effective medications for the management of both chronic pain states and AUD.