Over a hundred million of Americans suffer from chronic pain and over ten million of Americans suffer from alcohol abuse or dependence. There is a bidirectional relationship between chronic pain and alcohol dependence. Thus, alcohol dependence is a major predictor of severity of chronic pain, and people with chronic pain conditions are more likely to use alcohol for pain relief. Unfortunately, a mechanistic understanding of alcohol-related pain sensitivity is lacking. Our studies have identified increased pain sensitivity in mice during withdrawal from voluntary alcohol self-administration. Consumption of alcohol in these mice reversed mechanical hypersensitivity produced by alcohol withdrawal. The increased pain sensitivity in mice undergoing withdrawal is consistent with increased pain in alcohol-dependent patients. In addition, we found increased pain sensitivity in control ?bystander? mice housed in the same room as mice undergoing alcohol withdrawal. The social transfer of hyperalgesia from mice undergoing withdrawal to the bystander mice involved olfactory cues. Such social transfer of hyperalgesia could affect co-dependent family members of alcoholic patients. Immunohistochemical analysis revealed differential activation of dorsomedial hypothalamus, anterior cingulate and anterior insular cortex in these animals. We hypothesize that the identified brain regions are differentially involved in alcohol withdrawal-induced hyperalgesia and socially-transferred hyperalgesia. The goal of this proposal is to address this hypothesis and further characterize the phenomena of alcohol withdrawal- and social transfer-induced hyperalgesia. This goal will be achieved in three Specific Aims:
Aim 1 will further characterize the phenomenon of hyperalgesia in alcohol withdrawing and bystander mice by examining whether the observed thermal hyperalgesia is exaggerated in female bystander mice, involves negative affective states, anxiety or stress responses, or coexists with depression-like behaviors.
Aim 2 will test whether alcohol-induced activation of neuronal populations within dorsomedial hypothalamus is necessary and sufficient for regulation of pain sensitivity and alcohol drinking behavior in mice.
Aim 3 will test whether alcohol withdrawal and social transfer-induced activation of neurons of anterior cingulate and/or insula are necessary and sufficient for regulation of pain sensitivity.

Public Health Relevance

A bidirectional relationship exists between alcohol dependence and chronic pain. This proposal for the first time investigates neural mechanisms underlying increased pain sensitivity following voluntary alcohol drinking. Understanding these mechanisms will be insightful for development of treatments of alcohol dependence and dependence-induced chronic pain.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
Project #
Application #
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Regunathan, Soundar
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Health and Science University
Other Basic Sciences
Schools of Medicine
United States
Zip Code
Walcott, Andre T; Smith, Monique L; Loftis, Jennifer M et al. (2018) Social transfer of alcohol withdrawal-induced hyperalgesia in female prairie voles. Soc Neurosci 13:710-717
Ryabinin, Andrey E; Giardino, William J (2017) Contribution of Urocortin to the Development of Excessive Drinking. Int Rev Neurobiol 136:275-291
Smith, Monique L; Walcott, Andre T; Heinricher, Mary M et al. (2017) Anterior Cingulate Cortex Contributes to Alcohol Withdrawal- Induced and Socially Transferred Hyperalgesia. eNeuro 4:
Smith, Monique L; Hostetler, Caroline M; Heinricher, Mary M et al. (2016) Social transfer of pain in mice. Sci Adv 2:e1600855