title: μ-Opioid Receptor Gene A118 G Variants and Persistent Pain Symptoms Among Men and Women Experiencing Motor Vehicle Collision.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: TRYUMPH Research Program, Anesthesiology Department, University of North Carolina, Chapel Hill, North Carolina; Department of Anesthesiology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Linnstaedt
authors.affiliation: TRYUMPH Research Program, Anesthesiology Department, University of North Carolina, Chapel Hill, North Carolina; Department of Anesthesiology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: JunMei
authors.initials: J
authors.lastname: Hu
authors.affiliation: TRYUMPH Research Program, Anesthesiology Department, University of North Carolina, Chapel Hill, North Carolina; Department of Anesthesiology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Bortsov
authors.affiliation: TRYUMPH Research Program, Anesthesiology Department, University of North Carolina, Chapel Hill, North Carolina; Department of Anesthesiology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: April C
authors.initials: AC
authors.lastname: Soward
authors.affiliation: Department of Emergency Medicine, William Beaumont Hospital, Royal Oak, Michigan.
authors.forename: Robert
authors.initials: R
authors.lastname: Swor
authors.affiliation: Department of Emergency Medicine, Spectrum Health Butterworth Campus, Grand Rapids, Michigan.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Jones
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York.
authors.forename: David
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: David
authors.initials: D
authors.lastname: Peak
authors.affiliation: Department of Emergency Medicine, St Joseph Mercy Hospital, Ann Arbor, Michigan.
authors.forename: Robert
authors.initials: R
authors.lastname: Domeier
authors.affiliation: Department of Emergency Medicine, Baystate Medical Center, Springfield, Massachusetts.
authors.forename: Niels
authors.initials: N
authors.lastname: Rathlev
authors.affiliation: Department of Emergency Medicine, University of Florida College of Medicine/Jacksonville, Jacksonville, Florida.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Hendry
authors.affiliation: TRYUMPH Research Program, Anesthesiology Department, University of North Carolina, Chapel Hill, North Carolina; 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.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: McLean
mesh_terms: D000063:Accidents, Traffic / Q000523:psychology*; D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D010147:Pain Measurement; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000209:etiology / Q000235:genetics; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu
keywords: A118 G; Opioid-induced hyperalgesia; motor vehicle collision; pain; μ-opioid receptor 1
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