Chronic pain affects >50 million adults in the U.S. and represents a major socioeconomic and clinical challenge, in part because even the most efficacious of the current medications are limited by their side-effects profile. Similarly, alcoholism is a major problem with clinical treatments showing limited efficacy in reducing craving, relapse and abstinence rates. Clinical studies revealed a complicated association between chronic pain and alcohol dependence. Thus, chronic pain states significantly affect alcohol use patterns and promote the development of alcoholism, while long-term alcohol dependence induces symptoms of hyperalgesia and may exacerbate chronic pain arising from other sources. Alcohol's acute analgesic effects and chronic alcohol's hyperalgesic effects have been studied in animal models. However, the precise relationship between chronic pain and development of alcohol dependence has yet to be examined in animals, in part due to the lack of robust models that reflect the complex relationship between chronic pain and alcohol dependence in humans. In this exploratory project we propose 2 related specific aims designed to develop a robust animal model which reflects findings in humans and test specific hypotheses regarding the precise relationship between chronic pain and alcohol dependence. SA1 examines the dual consequences of alcohol dependence and chronic (neuropathic) pain development on voluntary alcohol drinking.
This aim will be achieved through the combined use of three well-characterized rat models of: a) alcohol dependence induced by forced chronic intermittent ethanol (CIE) administration, b) peripheral neuropathy induced by sciatic nerve entrapment (SNE) and c) voluntary (2-bottle choice, 2BC) regimen of ethanol (EtOH) consumption. SA2 examines if chronic pain- induced increases in voluntary EtOH intake is due to the analgesic effects of EtOH.
This aim will be achieved by first exposing rats to voluntary (2BC) regimen of EtOH consumption followed by EtOH withdrawal, SNE neuropathy induction and subsequent re-introduction of 2BC EtOH consumption. Upon 2BC EtOH re- introduction rats are provided with relief of neuropathy symptoms using unique novel analgesics without central nervous system side effects and their EtOH intake compared to that of vehicle-injected rats. In total, the experiments outlined in SA1 and SA2 will provide the much needed data on the role that chronic pain may play in the development and maintenance of alcohol dependence in robust, validated animal models. Future studies could make use of these models to further unravel the complex interactions between chronic pain and alcohol dependence, as well as test novel targeted treatments for these disorders.

Public Health Relevance

Chronic pain and alcoholism are serious disorders for which current treatments show limited effectiveness. Clinical evidence suggests a complicated association between chronic pain and alcohol dependence. Thus, chronic pain states significantly affect alcohol use patterns and promote the development of alcoholism, while long-term alcohol dependence enhances pain sensitivity and may exacerbate chronic pain arising from other sources. We propose studies using robust animal models which reflect findings in humans and test specific hypotheses regarding the precise relationship between chronic pain and alcohol dependence. These studies will help unravel the complex interactions between chronic pain and alcohol dependence, as well as test novel targeted treatments for these disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AA022408-01
Application #
8569864
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Regunathan, Soundar
Project Start
2013-09-01
Project End
2015-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$221,375
Indirect Cost
$77,625
Name
University of California Los Angeles
Department
Dentistry
Type
Schools of Dentistry
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095