MicroRNA 320a Predicts Chronic Axial and Widespread Pain Development Following Motor Vehicle Collision in a Stress-Dependent Manner

• Published in: The journal of orthopaedic and sports physical therapy Vol. 46; no. 10; pp. 911 - 919
• Main Authors: Linnstaedt, Sarah D, Riker, Kyle D, Walker, Margaret G, Nyland, Jennifer E, Zimny, Erin, Lewandowski, Christopher, Hendry, Phyllis L, Damiron, Kathia, Pearson, Claire, Velilla, Marc-Anthony, Jones, Jeffrey, Swor, Robert A, Domeier, Robert, McLean, Samuel A
• Format: Journal Article
• Language: English
• Published: United States 01.10.2016
• Subjects: Accidents, Traffic; Adult; Female; Humans; Male; MicroRNAs - blood; Musculoskeletal Pain - diagnosis; Musculoskeletal Pain - etiology; Neck Pain - diagnosis; Neck Pain - etiology; Prospective Studies; cervical spine; WAD; whiplash
• ISSN: 0190-6011; 1938-1344
• DOI: 10.2519/jospt.2016.6944

Study Design Prospective human cohort study combined with molecular studies. Background A microRNA is a small, noncoding RNA molecule that can play a role in disease onset. Recent studies found that circulating levels of microRNA 320a (miR-320a) are associated with musculoskeletal pain conditions and that miR-320a is stress responsive. Objectives To investigate whether circulating expression levels of miR-320a in the peritraumatic period predict persistent axial musculoskeletal pain 6 months after motor vehicle collision (MVC). Methods We evaluated whether (1) circulating miR-320a and related members of the miR-320a family predict axial musculoskeletal pain and other musculoskeletal pain outcomes 6 months following MVC, and (2) miR-320a regulates stress system and pain-related transcripts in cell culture. Given the wealth of data suggesting that biological mechanisms influencing pain outcomes are often sex and/or stress dependent, interactions between miR-320a, stress, and sex were evaluated. Results In primary analyses (n = 69), a significant crossover interaction was observed between the influence of circulating miR-320a and peritraumatic distress (β = -0.01, P = .002) on post-MVC axial musculoskeletal pain. Reduced peritraumatic miR-320a expression levels predicted axial musculoskeletal pain in distressed individuals (β = -0.12, P = .006) but not nondistressed individuals. In secondary analyses, miR-320a predicted widespread musculoskeletal pain, and related members of the miR-320a family also predicted axial and widespread musculoskeletal pain. In cell culture, miR-320a bound stress and pain-associated 3'UTR transcripts (FKBP5, ADCYAP1, PER2, and NR3C1). Conclusion These data suggest that miR-320a may help mediate regional and widespread changes in pain sensitivity after MVC. J Orthop Sports Phys Ther 2016;46(10):911-919. doi:10.2519/jospt.2016.6944.