Musculoskeletal pain (MSP) is a common sequela of traumatic stress exposure. While biologic factors contributing to chronic MSP after motor vehicle collision (MVC) have traditionally focused on tissue injury, increasing evidence suggests that neuro/stress/immune processes mediated by stress system activation may play a more dominant role. In a previous study we found that genetic variants in the hypothalamic-pituitary-adrenal (HPA) axis-related gene FKBP5 influence vulnerability to persistent MSP 6 weeks after MVC. In the present cohort study (n = 855) we evaluated whether genetic variants in several other important HPA axis-related genes, including the glucocorticoid receptor (NR3C1), corticotropin-releasing hormone receptor R1 (CRHR1), and corticotropin-releasing hormone binding protein (CRHBP), influence risk of chronic MSP over time after MVC._ENREF_4 Genetic polymorphism rs7718461 in the CRHBP gene showed significant association (p=0.0012) with overall pain severity during the year after MVC in regression models controlling for multiple comparisons. Two additional CRHBP alleles in high Linkage Disequilibrium with rs7718461 also showed trend-level significance. In secondary analyses, a significant interaction between this CRHBP locus (Minor Allele Frequency = 0.33) and time was observed (p = 0.015), with increasing effect observed over time following trauma. A significant CRHBP*FKBP5 interaction was also observed, with substantially increased MSP after MVC in those with a risk allele in both genes compared to either gene alone. The results of this study indicate that genetic variants in two different HPA axis genes predict chronic MSP severity following MVC, and support the hypothesis that the HPA axis is involved in chronic post-MVC MSP pathogenesis.
School of Medicine