MNPARC's strength lies in true bidirectional translation. We leverage human laboratory and clinical findings to drive mechanistic preclinical studies, while using those preclinical insights to strategically inform and refine human laboratory and clinical research. This powerful and collaborative approach allows the consortium to bridge basic and clinical science, accelerating discovery and ensuring that advances in understanding the interactions between pain and alcohol are both biologically grounded and directly relevant to human health.
Effects of pain on motivation to use alcohol, alcohol use topography, and recovery from AUD
Growing evidence indicates pain has an important influence on alcohol use. For people with AUD in recovery, pain has been shown to increase risk for return to use. At the same time, reductions in pain during early abstinence are associated with improvements in abstinence self-efficacy and reductions in craving. Our work suggests that pain may increase the reinforcing efficacy of alcohol and intensify the topography of alcohol use during self-paced drinking, especially in men, consistent with greater risk for alcohol-related problems. We are currently expanding on this work in three ways. First, we are conducting a large study characterizing the effect of pain on drinking topography both in the laboratory and in daily life in people with chronic orofacial pain. Second, we are collaborating with the University of Minnesota Department of Psychiatry to systematically assess the prevalence and severity of painful alcohol-induced neuropathy in treatment seekers with AUD. Finally, we are actively back-translating our results in human participants to preclinical rodent models to better assess potential neurobehavioral mechanisms underlying pain as an antecedent to alcohol use.
Pre-clinical models examining alcohol as an antecedent for chronic pain
Human data indicate that alcohol use is associated with increased likelihood of serious injury and emergency room visits. Patients with alcohol use disorder (AUD) prior to injury develop chronic pain at a higher rate compared with those without AUD. Our novel and innovative experimental model reverse translates these findings to better understand the behavioral and molecular mechanisms by which chronic alcohol acts as an antecedent for chronic pain. We find that voluntary, chronic intermittent alcohol consumption produces alcohol-induced mechanical hypersensitivity in both male and female mice, but alcohol-induced cold sensitivity occurred in female mice only. Chronic alcohol drinking in mice produces persistent pain after an acute pain stimulus, such as intraplantar capsaicin, or a chronic injury, such as a sciatic nerve crush in both males and females. The magnitude of injury-induced hypersensitivity was equal in both males and females, despite female mice drinking significantly more than males. Our results suggest that chronic voluntary alcohol consumption facilitates the transition to chronic pain by prolonging hypersensitivity and delaying recovery from injuries. This experimental paradigm enables investigations of mechanisms that make chronic alcohol consumption a risk factor for development of chronic pain.
Schorn R., Riedl M., Stone L.S., Lee A.M. & Vulchanova L. Chronic alcohol drinking delays recovery from capsaicin- and nerve injury-induced hypersensitivity in mice. Alcohol. 129, 123-133 (2025).
Alcohol-induced adaptations that facilitate the chronification of pain
Our research investigates how chronic alcohol consumption drives central and spinal neuroadaptations that promote the transition from acute to chronic pain. We are interested in alcohol-induced circuit-level changes in the brain and spinal cord, to determine how specific cell populations and neural connections contribute to alcohol-induced pain vulnerability. We are also interested in the impact of chronic-alcohol use on low back pain and intervertebral disc degeneration. In parallel, we are investigating epigenetic changes in chronic alcohol and chronic pain states to identify long-term changes that may contribute to alcohol facilitation of chronic pain. Together, this work aims to define the multiple pathways through which alcohol increases susceptibility to persistent pain and to identify novel therapeutic targets for intervention.