(304) - OPRM1 gene expression differentially predicts posttraumatic chronic pain in women and men

Abstract

Results of previous studies suggest that the expression of endogenous opioids in response to traumatic stress, and/or the influence of endogenous opioids on musculoskeletal pain (MSP) outcomes after traumatic stress exposure may differ in women vs. men. In the current prospective observational study we evaluated for potential sex differences in: (1) peritraumatic OPRM1 expression in response to motor vehicle collision (MVC) and (2) and the association between peritraumatic OPRM1 expression levels and chronic MSP outcomes following MVC. African American (AA) individuals ≥18 years of age presenting to one of twelve emergency departments (EDs) within 24 hours of MVC who did not have fracture or require hospital admission were enrolled. Blood was collected in the ED using PAXgene RNA tubes (n = 174) and MSP severity was assessed 6 weeks following MVC (0–10 NRS). The association between OPRM1 mRNA expression (identified via RNA sequencing) and post-MVC chronic MSP development was assessed using general linear models adjusting for age, ED study site, and exogenous opioid use. A significant interaction between OPRM1 mRNA expression levels and sex was observed (P = .026). In men, high expression levels of OPRM1 mRNA were significantly associated with increased MSP severity six weeks following MVC (5.52 vs 3.29, P = .018). In women, OPRM1 expression levels were not a significant predictor of 6-week post-MVC MSP levels (4.88 vs 5.13, P = .691). Of note, this difference in expression was independent of the well-studied A118G genetic variant in OPRM1, as all individuals examined had two copies of the major allele (due to low MAF in AA). Further studies are needed to better understand sex differences in the role of endogeneous vs. exogenous opioids in predicting chronic MSP development following traumatic stress exposure. Funding: NIH R01AR060852.