# Dissecting the role of ethanol-induced plasticity in the PAG to BNST pathway in pain-related behaviors

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $179,858

## Abstract

The high incidence of alcohol abuse that occurs in patients with chronic pain underscores the importance of
continued research towards effective treatments for both pain and alcohol use disorders. It has been found in
animal models that chronic alcohol exposure can drive adaptations in the brain, which drive increased pain-
related behaviors. Our long-term goal is to understand how chronic alcohol exposure can alter the neuronal
circuits that regulate pain-related behavior in order to develop more effective approaches to treat alcohol induced
pain. One region of particular interest for these studies is the periaqueductal gray (PAG). We have previously
shown that a subpopulation of dopamine neurons in the ventrolateral PAG (PAGDA) are activated by acute alcohol
and activation of these same neurons induces an anti-nociceptive effect in the hot-plate test. Furthermore, in
our preliminary data, we found that activation of the outputs to the bed nucleus of the stria terminalis (BNST)
could replicate this anti-nociceptive effect. These findings are noteworthy, as they identify a novel ascending
anti-nociceptive pathway (PAGDA to BNST) distinct from the well-characterized descending anti-nociceptive
pathway (PAG to Medulla). In keeping with the critical role of the PAGDA to BNST pathway, we found that viral
deletion of CRF from the BNST can alter pain related behaviors. In addition, we have found that intermittent
alcohol drinking can drive changes in pain-related behavior in mice. Taken together, these studies support the
testable hypothesis that intermittent alcohol drinking drives alterations in pain related behavior, in part through
disruptions in the PAGDA to BNST pathway, and that in vivo activation of this pathway can ameliorate alcohol-
induced hyperalgesia.

## Key facts

- **NIH application ID:** 9926793
- **Project number:** 5R21AA027460-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Thomas L. Kash
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $179,858
- **Award type:** 5
- **Project period:** 2019-05-10 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926793

## Citation

> US National Institutes of Health, RePORTER application 9926793, Dissecting the role of ethanol-induced plasticity in the PAG to BNST pathway in pain-related behaviors (5R21AA027460-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9926793. Licensed CC0.

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