Citation

Meloto CB, Bortsov AV, Bair E, Helgeson E, Ostrom C, Smith S, Dubner R, Slade GD, Fillingim RB, Greenspan JD, Ohrbach R, Maixner W, McLean S, Diatchenko L. Pain 2015; 157(4): 858-867.

Affiliation

aThe Alan Edwards Centre for Research on Pain, McGill University, McGill University Genome Building, 740 Dr. Penfield Avenue, Room 2200, Montreal, QC, H3A 0G1, Canada bDepartment of Anesthesiology, University of North Carolina at Chapel Hill, 101 Manning Drive, Medical School Wing C, Chapel Hill, NC 27599-7010, USA cCenter for Pain Research and Innovation, University of North Carolina at Chapel Hill; Department of Endodontics, University of North Carolina at Chapel Hill, Koury Oral Health Sciences Building, CB #7455, Chapel Hill, NC 27599-7450, USA dDepartment of Biostatistics, University of North Carolina at Chapel Hill, Koury Oral Health Sciences Building, CB #7450, Chapel Hill, NC 27599-7450, USA eDepartment of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD, USA; Brotman Facial Pain Center, University of Maryland School of Dentistry, Baltimore, MD, USA; 650 W. Baltimore St., Room 8251, Dental-8 South Baltimore, MD 21201, USA fDepartment of Community Dentistry and Behavioral Science, University of Florida, College of Dentistry, and Pain, Research and Intervention Center of Excellence, Clinical and Translational Research Building (CTRB), Room 3216, 2004 Mowry Road, PO Box 100404,Gainesville, FL, 32610-0404, USA. gDepartment of Neural and Pain Sciences, and Brotman Facial Pain Clinic, University of Maryland School of Dentistry, 650 W Baltimore St, 8th Floor South, Baltimore, MD, 21201, USA. hDepartment of Oral Diagnostic Sciences, University at Buffalo, 355 Squire Hall, Buffalo, NY, 14214, USA.

Copyright

(Copyright © 2015, Lippincott, Williams and Wilkins)

DOI

10.1097/j.pain.0000000000000449

PMID

26675825

Abstract

Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants impact enzymatic activity and affect pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its association with pain phenotypes are not always replicated. Here, we investigated if interactions among functional COMT haplotypes, stress, and sex can modify the effect of COMT genetic variants on pain sensitivity. We tested these interactions in a cross-sectional study including two cohorts, one of 2,972 subjects tested for thermal pain sensitivity (OPPERA) and one of 948 subjects with clinical acute pain after motor vehicle collision (post-MVC). In both cohorts, the COMT high pain sensitivity (HPS) haplotype showed robust interaction with stress and number of copies of the HPS haplotype was positively associated with pain sensitivity in non-stressed individuals, but not in stressed individuals. In the post-MVC cohort, there was additional modification by sex: the HPS-stress interaction was apparent in males, but not in females. In summary, our findings indicate that stress and sex should be evaluated in association studies aiming to investigate the effect of COMT genetic variants on pain sensitivity.

Language: en