title: Polymorphisms in the glucocorticoid receptor co-chaperone FKBP5 predict persistent musculoskeletal pain after traumatic stress exposure.
abstract: Individual vulnerability factors influencing the function of the hypothalamic-pituitary-adrenal axis may contribute to the risk of the development of persistent musculoskeletal pain after traumatic stress exposure. The objective of the study was to evaluate the association between polymorphisms in the gene encoding FK506 binding protein 51, FKBP5, a glucocorticoid receptor co-chaperone, and musculoskeletal pain severity 6 weeks after 2 common trauma exposures. The study included data from 2 prospective emergency department-based cohorts: a discovery cohort (n=949) of European Americans experiencing motor vehicle collision and a replication cohort of adult European American women experiencing sexual assault (n=53). DNA was collected from trauma survivors at the time of initial assessment. Overall pain and neck pain 6 weeks after trauma exposure were assessed using a 0-10 numeric rating scale. After adjustment for multiple comparisons, 6 FKBP5 polymorphisms showed significant association (minimum P<0.0001) with both overall and neck pain in the discovery cohort. The association of rs3800373, rs9380526, rs9394314, rs2817032, and rs2817040 with neck pain and/or overall pain 6 weeks after trauma was replicated in the sexual assault cohort, showing the same direction of the effect in each case. The results of this study indicate that genetic variants in FKBP5 influence the severity of musculoskeletal pain symptoms experienced during the weeks after motor vehicle collision and sexual assault. These results suggest that glucocorticoid pathways influence the development of persistent posttraumatic pain, and that such pathways may be a target of pharmacologic interventions aimed at improving recovery after trauma.
authors.affiliation: TRYUMPH Research Program, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Bortsov
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Smith
authors.forename: Luda
authors.initials: L
authors.lastname: Diatchenko
authors.forename: April C
authors.initials: AC
authors.lastname: Soward
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Ulirsch
authors.forename: Catherine
authors.initials: C
authors.lastname: Rossi
authors.forename: Robert A
authors.initials: RA
authors.lastname: Swor
authors.forename: William E
authors.initials: WE
authors.lastname: Hauda
authors.forename: David A
authors.initials: DA
authors.lastname: Peak
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Jones
authors.forename: Debra
authors.initials: D
authors.lastname: Holbrook
authors.forename: Niels K
authors.initials: NK
authors.lastname: Rathlev
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Foley
authors.forename: David C
authors.initials: DC
authors.lastname: Lee
authors.forename: Renee
authors.initials: R
authors.lastname: Collette
authors.forename: Robert M
authors.initials: RM
authors.lastname: Domeier
authors.forename: Phyllis L
authors.initials: PL
authors.lastname: Hendry
authors.forename: Samuel A
authors.initials: SA
authors.lastname: McLean
mesh_terms: D000063:Accidents, Traffic / Q000523:psychology; D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D059352:Musculoskeletal Pain / Q000209:etiology* / Q000235:genetics*; D010147:Pain Measurement; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012742:Sex Offenses / Q000523:psychology; D040921:Stress Disorders, Traumatic / Q000145:classification / Q000150:complications*; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5