Author ORCID Identifier
https://orcid.org/0000-0002-1742-1894
Defense Date
2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Human Genetics
First Advisor
Michael Miles
Second Advisor
M Imad Damaj
Abstract
Alcohol use disorder and pain are complex public health concerns affecting millions of people, and these conditions are often characterized by a bidirectional relationship. People experiencing pain may drink alcohol for its analgesic effects. In turn, excessive consumption of alcohol can lead to conditions that cause pain, leading to an escalating feedback loop of pain and alcohol use. Negating this cycle requires a nuanced understanding of the mechanisms underlying alcohol analgesia, which are presently not fully understood. The Miles and Damaj labs have previously shown that ethanol-induced antinociception is moderately heritable in mice, indicating a genetic component to the trait. Here we identify specific genes and pathways contributing to these analgesic effects by leveraging complementary behavioral genetics and time-dependent brain gene expression studies. We assayed strains from the BXD panel of recombinant inbred mice to highlight genomic loci linked with post-ethanol thermal nociception and ethanol analgesia-like responses, then prioritized positional candidate genes in these regions with a battery of systems genetics approaches. Our results reveal Myo6 as a strong ethanol analgesia candidate gene through combined evidence of our present work, historic BXD gene expression correlations, roles for the gene in ethanol consumption in other rodent models, and significant associations in human GWAS literature. We additionally describe correlations between post-ethanol nociception and the expression of genes implicated in myelination, protein transport, and other biological processes that could be modulating ethanol analgesia. Finally, we investigate transcriptomic profiles of two common pain conditions, alcohol- and chemotherapy- 2 induced peripheral neuropathy, to characterize toxin-specific and overlapping mechanisms of pathophysiology. The work in this dissertation contributes to our understanding of both ethanol as an analgesic and the transcriptomic correlates of two pain conditions, and it prioritizes specific targets for future research into these phenotypes.
Rights
© Walker Rogers
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
10-28-2025