Peritraumatic Circulating 17β-Estradiol as a Resiliency Factor for Chronic Pain Outcomes in Women Following Trauma

Background: Musculoskeletal pain is common following traumatic/stressful life events and is more common in women than men. However, resiliency factors that predict improved chronic posttraumatic musculoskeletal pain (CPMP) in women are poorly understood. In the current study, we examined whether peritraumatic circulating 17β-estradiol (E2) levels influence CPMP trajectories in women. Methods: Peritraumatic E2 levels were measured via ELISA in plasma samples (n=167) derived from three multiethnic longitudinal cohort studies of trauma survivors. These cohorts enrolled individuals experiencing motor vehicle collision (MVC, n=89), sexual assault (n=64), and major thermal burn injury (n=14). CPMP (0-10 numeric rating scale) was assessed 6-weeks, 6-months, and 1-year following traumatic stress exposure. Repeated measures mixed models were used to test the relationship between log-transformed E2 levels and CPMP. Secondary analyses of MVC cohort gene expression data (n=37) evaluated mediating transcripts and associated biological pathways (Ingenuity, IPA). Results: An inverse relationship between peritraumatic E2 and the development of CPMP was observed (β= -0.353, p=0.033) such that women with high E2 at the time of trauma had less CPMP over the following year. Secondary analyses identified 250 mRNA that mediated the relationship between E2 and CPMP; initial enrichment analyses identified eIF2 signaling as a top pathway through which E2 might influence CPMP development. Conclusions: Increased peritraumatic E2 levels predict improved CPMP outcomes in women