Highlights
- •We examined the effect of OPRM1 A118 G on persistent pain following motor vehicle collision (MVC) stress.
- •Women with a G allele and distress at the time of MVC had reduced pain at 6 weeks.
- •Men with a G allele had increased pain 6 weeks following MVC.
- •Results show a sex-dependent effect of A118 G on pain development following stress.
- •Effect of OPRM1 allele on pain after stress suggests endogenous opioid-induced hyperalgesia mechanism.
Abstract
The μ-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 posttraumatic musculoskeletal pain (MSP). In this prospective observational
study, we evaluated the hypothesis that individuals with an AG or GG genotype at the
OPRM1 A118 G allele, which results in a reduced response to opioids, would have less severe
MSP 6 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 6-week evaluation of overall MSP
severity (0–10 numeric rating scale). In linear regression modeling, a significant
A118 G Allele × Sex interaction was observed: an AG/GG genotype predicted reduced
MSP severity among women with substantial peritraumatic distress (β = –.925, P = .014) but not among all women. In contrast, men with an AG/GG genotype experienced
increased MSP severity at 6 weeks (β = .827, P = .019). Further studies are needed to understand the biologic mechanisms mediating
observed sex differences in A118 G 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.
Key words
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Article info
Publication history
Published online: April 01, 2015
Accepted:
March 27,
2015
Received in revised form:
March 27,
2015
Received:
February 4,
2015
Footnotes
Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R01AR056328.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
No conflicts of interest exist for any of the authors.
The project described was supported by Award Number R01AR056328 from the National Institute of Arthritis and Musculoskeletal and Skin diseases.
Identification
Copyright
© 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.
