title: Summary of findings from the OPPERA prospective cohort study of incidence of first-onset temporomandibular disorder: implications and future directions.
abstract: Papers in this issue investigate when and how putative risk factors influence development of first-onset, painful temporomandibular disorder (TMD). The results represent first findings from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort study that monitored 2,737 men and women aged 18 to 44 years recruited at 4 U.S. study sites. During a median 2.8-year follow-up period, 260 participants developed TMD. The average incidence rate of 4% per annum was influenced by a broad range of phenotypic risk factors including sociodemographic characteristics, health status, clinical orofacial factors, psychological functioning, pain sensitivity, and cardiac autonomic responses. A novel method of multivariable analysis used random forest models to simultaneously evaluate contributions of all 202 phenotypic variables. Variables from the health status domain made the greatest contribution to TMD incidence, followed closely by psychological and clinical orofacial domains. However, only a few measures of pain sensitivity and autonomic function contributed to TMD incidence, and their effects were modest. Meanwhile, age and study site were independent predictors of TMD incidence, even after controlling for other phenotypes. Separate analysis of 358 genes that regulate pain found several novel genetic associations with intermediate phenotypes that, themselves, are risk factors for TMD, suggesting new avenues to investigate biological pathways contributing to TMD.
  
  
  CONCLUSIONS
  Collectively, the papers in this issue demonstrate that TMD is a complex disorder with multiple causes consistent with a biopsychosocial model of illness. It is a misnomer and no longer appropriate to regard TMD solely as a localized orofacial pain condition.
authors.affiliation: Regional Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Dental Ecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: gary_slade@dentistry.unc.edu.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Slade
authors.forename: Roger B
authors.initials: RB
authors.lastname: Fillingim
authors.forename: Anne E
authors.initials: AE
authors.lastname: Sanders
authors.forename: Eric
authors.initials: E
authors.lastname: Bair
authors.forename: Joel D
authors.initials: JD
authors.lastname: Greenspan
authors.forename: Richard
authors.initials: R
authors.lastname: Ohrbach
authors.forename: Ronald
authors.initials: R
authors.lastname: Dubner
authors.forename: Luda
authors.initials: L
authors.lastname: Diatchenko
authors.forename: Shad B
authors.initials: SB
authors.lastname: Smith
authors.forename: Charles
authors.initials: C
authors.lastname: Knott
authors.forename: William
authors.initials: W
authors.lastname: Maixner
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D005157:Facial Pain / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D013705:Temporomandibular Joint Disorders / Q000453:epidemiology* / Q000209:etiology
keywords: Temporomandibular disorder; clinical pain; cohort studies; comordid conditions; epidemiology; genetics; pain sensitivity; psychological factors