Citation

Linnstaedt SD, Hu J, Bortsov AV, Soward AC, Swor R, Jones JCH, Lee D, Peak D, Domeier RM, Rathlev N, Hendry P, McLean SA. J. Pain 2015; 16(7): 637-644.

Affiliation

TRYUMPH Research Program; Department of Anesthesiology, University of North Carolina, Chapel Hill, North Carolina; Department of Emergency Medicine, University of North Carolina, Chapel Hill, North Carolina. Electronic address: smclean@aims.unc.edu.

Copyright

(Copyright © 2015, Elsevier Publishing)

DOI

10.1016/j.jpain.2015.03.011

PMID

25842347

Abstract

The mu-opioid receptor 1 (OPRM1) binds endogenous opioids. Increasing evidence suggests that endogenous OPRM1 agonists released at the time of trauma may contribute to the development of post-traumatic musculoskeletal pain (MSP). In this prospective observational study we evaluated the hypothesis that individuals with an AG or GG genotype at the OPRM1 A118G allele, which results in a reduced response to opioids, would have less severe MSP six weeks after motor vehicle collision (MVC). Based on previous evidence, we hypothesized that this effect would be sex-dependent and most pronounced among women with substantial peritraumatic distress. European American men and women ≥18 years of age presenting to the emergency department after MVC and discharged to home after evaluation (n=948) were enrolled. Assessments included genotyping and six week evaluation of overall MSP severity (0-10NRS). In linear regression modeling a significant A118G allele x sex interaction was observed: an AG/GG genotype predicted reduced MSP severity among women with substantial peritraumatic distress (β= -0.925, p=0.014), but not among all women. In contrast, men with an AG/GG genotype experienced increased MSP severity at six weeks (β=0.827, p=0.019). Further studies are needed to understand biologic mechanisms mediating observed sex differences in A118G effects. PERSPECTIVE: These results suggest a sex-dependent mechanism by which an emotional response to trauma (distress) contributes to a biologic mechanism (endogenous opioid release) that increases MSP in the weeks after stress exposure. These results also support the hypothesis that endogenous opioids influence pain outcomes differently in men and women.

Language: en