# Elucidating causal mechanisms of ethanol-induced analgesia in BXD recombinant inbred mouse lines

> **NIH NIH F31** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $43,404

## Abstract

Project Summary
Alcohol use disorder (AUD) and pain are major public health problems affecting millions of people in the United
States. More than 14 million Americans met the diagnostic criteria for AUD in 2019, and 50 million people in
the United States were estimated to have a chronic pain condition. These public health crises are related, as
people experiencing pain often report using alcohol to manage pain symptoms, and people with chronic pain
are at an elevated risk for developing AUD. Drinking alcohol to alleviate pain is a maladaptive strategy and
may lead to withdrawal-induced hyperalgesia, peripheral neuropathy, and AUD. While alcohol confers
analgesic effects in a dose-dependent manner, genetic differences mean that not every person experiences
this analgesia to the same degree. Previous research has revealed moderate-to-strong heritability (h2=0.42) for
ethanol-induced analgesia in C57BL/6J and DBA/2J mice, but the genes underlying this relationship are still
poorly characterized. Studies in rodent models have revealed evidence that opioid receptor systems, GIRK2
potassium channels, and GABAergic signaling pathways all have roles in ethanol analgesia, but no whole-
genome interrogations have been conducted. This project aims to identify candidate genes modulating alcohol-
induced analgesia using complementary genetic, behavioral and transcriptomic experiments in genetically
informative BXD mouse populations. By mapping quantitative trait loci (QTL) for both basal and post-ethanol
hot plate latency with BXD strains, we will identify genomic loci linked with variation in ethanol-induced
analgesia. As an additional genome-wide approach, prefrontal cortex and periaqueductal gray samples from
high- and low-ethanol analgesia BXD strains will be studied by RNA-seq. We will perform weighted gene co-
expression network analysis (WGCNA) to identify differentially expressed genes in these two analgesia
groups. By combining evidence from behavioral, statistical, and molecular methodologies, we will select the
strongest ethanol analgesia candidate gene for experimental verification using either overexpression or
knockout mouse models. This proposal comprises an investigative progression from identifying candidate
genes by QTL mapping, to elucidating gene expression patterns in critical brain regions, to validating ethanol
analgesia candidate genes. It represents an outstanding training opportunity for the candidate to design and
perform a suite of systems genetics and animal behavioral experiments and contribute to the scientific
understanding of substance-induced analgesia.

## Key facts

- **NIH application ID:** 10938304
- **Project number:** 5F31AA030918-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Walker David Rogers
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $43,404
- **Award type:** 5
- **Project period:** 2023-09-10 → 2026-09-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938304

## Citation

> US National Institutes of Health, RePORTER application 10938304, Elucidating causal mechanisms of ethanol-induced analgesia in BXD recombinant inbred mouse lines (5F31AA030918-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10938304. Licensed CC0.

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