title: Painful Temporomandibular Disorder: Decade of Discovery from OPPERA Studies.
abstract: In 2006, the OPPERA project (Orofacial Pain: Prospective Evaluation and Risk Assessment) set out to identify risk factors for development of painful temporomandibular disorder (TMD). A decade later, this review summarizes its key findings. At 4 US study sites, OPPERA recruited and examined 3,258 community-based TMD-free adults assessing genetic and phenotypic measures of biological, psychosocial, clinical, and health status characteristics. During follow-up, 4% of participants per annum developed clinically verified TMD, although that was a "symptom iceberg" when compared with the 19% annual rate of facial pain symptoms. The most influential predictors of clinical TMD were simple checklists of comorbid health conditions and nonpainful orofacial symptoms. Self-reports of jaw parafunction were markedly stronger predictors than corresponding examiner assessments. The strongest psychosocial predictor was frequency of somatic symptoms, although not somatic reactivity. Pressure pain thresholds measured at cranial sites only weakly predicted incident TMD yet were strongly associated with chronic TMD, cross-sectionally, in OPPERA's separate case-control study. The puzzle was resolved in OPPERA's nested case-control study where repeated measures of pressure pain thresholds revealed fluctuation that coincided with TMD's onset, persistence, and recovery but did not predict its incidence. The nested case-control study likewise furnished novel evidence that deteriorating sleep quality predicted TMD incidence. Three hundred genes were investigated, implicating 6 single-nucleotide polymorphisms (SNPs) as risk factors for chronic TMD, while another 6 SNPs were associated with intermediate phenotypes for TMD. One study identified a serotonergic pathway in which multiple SNPs influenced risk of chronic TMD. Two other studies investigating gene-environment interactions found that effects of stress on pain were modified by variation in the gene encoding catechol O-methyltransferase. Lessons learned from OPPERA have verified some implicated risk factors for TMD and refuted others, redirecting our thinking. Now it is time to apply those lessons to studies investigating treatment and prevention of TMD.
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Dental Ecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA gary_slade@unc.edu.
authors.forename: G D
authors.initials: GD
authors.lastname: Slade
authors.affiliation: Department of Oral Diagnostic Sciences, University at Buffalo, Buffalo, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ohrbach
authors.affiliation: Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD, USA Brotman Facial Pain Clinic, University of Maryland School of Dentistry, Baltimore, MD, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Greenspan
authors.affiliation: Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Fillingim
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Endodontics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: E
authors.initials: E
authors.lastname: Bair
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Dental Ecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Sanders
authors.affiliation: Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Dubner
authors.affiliation: The Allan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Diatchenko
authors.affiliation: The Allan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
authors.forename: C B
authors.initials: CB
authors.lastname: Meloto
authors.affiliation: Center for Translational Pain Medicine, Duke University, Durham, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.affiliation: Center for Translational Pain Medicine, Duke University, Durham, NC, USA.
authors.forename: W
authors.initials: W
authors.lastname: Maixner
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D005157:Facial Pain / Q000235:genetics* / Q000503:physiopathology*; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D010147:Pain Measurement; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D013705:Temporomandibular Joint Disorders / Q000235:genetics* / Q000503:physiopathology*; D014481:United States
keywords: chronic pain; cohort studies; gene-environment interaction; human COMT protein; pain threshold; psychological stress