ArticlePolymorphisms in the glucocorticoid receptor co-chaperone FKBP5 predict persistent musculoskeletal pain after traumatic stress exposureBortsov, Andrey V.a,b,1; Smith, Jennifer E.a,b,1; Diatchenko, Ludac; Soward, April C.a,b; Ulirsch, Jacob C.a,b; Rossi, Catherined; Swor, Robert A.e; Hauda, William E.f; Peak, David A.g; Jones, Jeffrey S.h; Holbrook, Debrai; Rathlev, Niels K.j; Foley, Kelly A.k; Lee, David C.l; Collette, Reneem; Domeier, Robert M.n; Hendry, Phyllis L.o; McLean, Samuel A.a,b,p,*Author Information Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. aTRYUMPH Research Program, University of North Carolina, Chapel Hill, NC, USA bDepartment of Anesthesiology, University of North Carolina, Chapel Hill, NC, USA cRegional Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, NC, USA dForensic Nursing Program, Department of Medicine, Cone Health System, Greensboro, NC, USA eDepartment of Emergency Medicine, William Beaumont Hospital, Royal Oak, MI, USA fForensic Assessment and Consultation Teams, Inova Fairfax Hospital, Falls Church, VA, USA gDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA hDepartment of Emergency Medicine, Spectrum Health System, Grand Rapids, MI, USA iSANE [Sexual Assault Nurse Examiner] Program, Mercy Medical Center, Baltimore, MD, USA jDepartment of Emergency Medicine, Baystate Medical Center, Springfield, MA, USA kDepartment of Emergency Medicine, Sentara Norfolk Hospital, Norfolk, VA, USA lDepartment of Emergency Medicine, North Shore University Hospital, Manhasset, NY, USA mSANE Program, Mission Health System, Asheville, NC, USA nDepartment of Emergency Medicine, Saint Joseph Mercy Health System, Ypsilanti, MI, USA oDepartment of Emergency Medicine, University of Florida, Jacksonville, FL, USA pDepartment of Emergency Medicine, University of North Carolina, Chapel Hill, NC, USA *Corresponding author. Address: University of North Carolina, Medical School Wing C CB#7010, Chapel Hill, NC 27599-7010, USA. Tel.: +1 919 843 5931; fax: +1 919 966 7193. 1The first two authors contributed equally to this manuscript. E-mail address: firstname.lastname@example.org Submitted March 22, 2013; revised April 18, 2013; accepted April 22, 2013. Pain: August 2013 - Volume 154 - Issue 8 - p 1419-1426 doi: 10.1016/j.pain.2013.04.037 Buy Metrics Abstract An association is demonstrated between genetic polymorphisms in the gene coding for a key regulatory molecule in the hypothalamic-pituitary-adrenal axis and persistent pain after trauma. 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. © 2013 Lippincott Williams & Wilkins, Inc.