CRHBP polymorphisms predict chronic pain development following motor vehicle collision.

Journal Article (Journal Article)

Musculoskeletal pain (MSP) is a common sequela of traumatic stress exposure. While biological 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. 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 with either gene alone. The results of this study indicate that genetic variants in 2 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.

Full Text

Duke Authors

Cited Authors

  • Linnstaedt, SD; Bortsov, AV; Soward, AC; Swor, R; Peak, DA; Jones, J; Rathlev, N; Lee, DC; Domeier, R; Hendry, PL; McLean, SA

Published Date

  • January 2016

Published In

Volume / Issue

  • 157 / 1

Start / End Page

  • 273 - 279

PubMed ID

  • 26447706

Pubmed Central ID

  • PMC4955812

Electronic International Standard Serial Number (EISSN)

  • 1872-6623

Digital Object Identifier (DOI)

  • 10.1097/j.pain.0000000000000374


  • eng

Conference Location

  • United States