Orofacial Pain : Prospective Evaluation And Risk Assessment Research Articles

Pain Sensitivity and Autonomic Factors Associated With Development of TMD: The OPPERA Prospective Cohort Study

Multiple studies report that individuals with chronic temporomandibular disorder (TMD) have enhanced sensitivity to experimental pain. Additionally, chronic TMD cases show altered autonomic function, including elevated heart rate and reduced heart rate variability. However, causal inferences regarding the association between TMD and pain sensitivity and autonomic function cannot be drawn from these cross-sectional observations. The prospective Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study examines whether measures of pain sensitivity or cardiac autonomic function provide predictive value in TMD incidence. A cohort of 2,737 initially TMD-free participants was followed for up to 5.2 years, during which time 260 developed first-onset TMD. Fourteen of 39 experimental pain measures produced significant hazard ratios, such that greater pain sensitivity was associated with greater TMD incidence. A single autonomic measure—heart rate at rest—was also associated significantly with greater TMD incidence. In contrast, using the same measures of pain sensitivity and cardiac autonomic function, we previously reported a larger group of variables that was significantly associated with chronic TMD in the OPPERA case-control study. Future studies should investigate whether premorbid pain sensitivity or autonomic function more specifically predicts risk of developing chronic TMD than first-onset TMD. PerspectiveOur previous case-control studies showed that associations with both pain sensitivity and cardiac autonomic function are profound in chronic TMD cases. Here we show that some measures of enhanced pain sensitivity contribute modestly to the risk of developing TMD whereas autonomic dysregulation appears to confer little or no risk for TMD incidence.

General Health Status and Incidence of First-Onset Temporomandibular Disorder: The OPPERA Prospective Cohort Study

Temporomandibular disorder (TMD) overlaps with other health conditions, but no study has examined which of these conditions increase the risk of developing first-onset TMD. The authors prospectively evaluated the relationship between health status at enrollment and subsequent incidence of TMD in 2,722 men and women. Participants aged 18 to 44 years had no history of TMD and were clinically free of TMD when enrolled in 2006 to 2008 at 4 U.S. study sites in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort study. First-onset examiner-classified TMD developed in 260 people over a median 2.8 years of follow-up. Cox regression estimated the association between health conditions and TMD incidence while accounting for potential confounders. Incidence of first-onset TMD was 50% higher for people with low back pain (adjusted hazard ratio [AHR] = 1.50, 95% confidence limits [CLs]: 1.08, 2.10) and 75% higher for people with genital pain symptoms (AHR = 1.75, 95% CLs = 1.04, 2.93) than people without a history of these pain disorders. Digit ratio, a marker of intrauterine exposure to sex hormones, was significantly associated with TMD incidence. Other independent predictors of first-onset TMD were sleep disturbance and cigarette smoking. These findings reveal multiple influences of health status on incidence of first-onset TMD. PerspectiveThis article examines health conditions that commonly overlap with TMD to determine which ones predict first-onset TMD. A history of low back pain and genital pain conditions at baseline were important predictors. Novel findings were that disrupted sleep and conditions in utero may increase incidence of first-onset TMD.

Summary of Findings From the OPPERA Prospective Cohort Study of Incidence of First-Onset Temporomandibular Disorder: Implications and Future Directions

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. PerspectiveCollectively, 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.

Potential Autonomic Risk Factors for Chronic TMD: Descriptive Data and Empirically Identified Domains from the OPPERA Case-Control Study

Several case-control studies have been conducted that examine the association between autonomic variables and persistent pain conditions; however, there is a surprising dearth of published studies in this area that have focused on temporomandibular disorders (TMD). The current study presents autonomic findings from the baseline case-control study of the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) cooperative agreement. Measures of arterial blood pressure, heart rate, heart rate variability, and indirect measures of baroreflex sensitivity were assessed at rest and in response to a physical (orthostatic) and psychological (Stroop) stressors in 1,633 TMD-free controls and 185 TMD cases. In bivariate and demographically adjusted analyses, greater odds of TMD case status were associated with elevated heart rates, reduced heart rate variability, and reduced surrogate measures of baroreflex sensitivity across all experimental procedures. Principal component analysis was undertaken to identify latent constructs revealing 5 components. These findings provide evidence of associations between autonomic factors and TMD. Future prospective analyses in the OPPERA cohort will determine if the presence of these autonomic factors predicts increased risk for developing new onset TMD. Perspective This article reports autonomic findings from the OPPERA Study, a large prospective cohort study designed to discover causal determinants of TMD pain. Findings indicate statistically significant differences between TMD cases and controls across multiple autonomic constructs at rest and during both physical and psychologically challenging conditions. Future analyses will determine whether these autonomic factors increase risk for new onset TMD.

Clinical Findings and Pain Symptoms as Potential Risk Factors for Chronic TMD: Descriptive Data and Empirically Identified Domains from the OPPERA Case-Control Study

Clinical characteristics might be associated with temporomandibular disorders (TMD) because they are antecedent risk factors that increase the likelihood of a healthy person developing the condition or because they represent signs or symptoms of either subclinical or overt TMD. In this baseline case-control study of the multisite Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) project, 1,633 controls and 185 cases with chronic, painful TMD completed questionnaires and received clinical examinations. Odds ratios measuring association between each clinical factor and TMD were computed, with adjustment for study-site as well as age, sex, and race/ethnicity. Compared to controls, TMD cases reported more trauma, greater parafunction, more headaches and other pain disorders, more functional limitation in using the jaw, more nonpain symptoms in the facial area, more temporomandibular joint noises and jaw locking, more neural or sensory medical conditions, and worse overall medical status. They also exhibited on examination reduced jaw mobility, more joint noises, and a greater number of painful masticatory, cervical, and body muscles upon palpation. The results indicated that TMD cases differ substantially from controls across almost all variables assessed. Future analyses of follow-up data will determine whether these clinical characteristics predict increased risk for developing first-onset pain-related TMD Perspective Clinical findings from OPPERA’s baseline case-control study indicate significant differences between chronic TMD cases and controls with respect to trauma history, parafunction, other pain disorders, health status, and clinical examination data. Future analyses will examine their contribution to TMD onset.

Potential Psychosocial Risk Factors for Chronic TMD: Descriptive Data and Empirically Identified Domains from the OPPERA Case-Control Study

Case-control studies have consistently associated psychosocial factors with chronic pain in general, and with temporomandibular disorders (TMD) specifically. Moreover, a handful of prospective studies suggest that preexisting psychosocial characteristics represent risk factors for new onset TMD. The current study presents psychosocial findings from the baseline case-control study of the Orofacial Pain Prospective Evaluation and Risk Assessment (OPPERA) cooperative agreement. For this study, 1,633 TMD-free controls and 185 TMD cases completed a battery of psychosocial instruments assessing general psychosocial adjustment and personality, affective distress, psychosocial stress, somatic awareness, and pain coping and catastrophizing. In bivariate and demographically adjusted analyses, odds of TMD were associated with higher levels of psychosocial symptoms, affective distress, somatic awareness, and pain catastrophizing. Among controls, significant gender and ethnic group differences in psychosocial measures were observed, consistent with previous findings. Principal component analysis was undertaken to identify latent constructs revealing 4 components: stress and negative affectivity, global psychosocial symptoms, passive pain coping, and active pain coping. These findings provide further evidence of associations between psychosocial factors and TMD. Future prospective analyses in the OPPERA cohort will determine if the premorbid presence of these psychosocial factors predicts increased risk for developing new onset TMD. Perspective This article reports baseline psychosocial findings from the OPPERA Study, a large prospective cohort study designed to discover causal determinants of TMD pain. Findings indicate significant differences between TMD cases and TMD-free controls across multiple psychosocial constructs, and future analyses will determine whether these psychosocial factors increase risk for new onset TMD.

Potential Genetic Risk Factors for Chronic TMD: Genetic Associations from the OPPERA Case Control Study

Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a few genes have been associated with temporomandibular disorders (TMD). This study evaluated 358 genes involved in pain processes, comparing allelic frequencies between 166 cases with chronic TMD and 1,442 controls enrolled in the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study cooperative agreement. To enhance statistical power, 182 TMD cases and 170 controls from a similar study were included in the analysis. Genotyping was performed using the Pain Research Panel, an Affymetrix gene chip representing 3,295 single nucleotide polymorphisms, including ancestry-informative markers that were used to adjust for population stratification. Adjusted associations between genetic markers and TMD case status were evaluated using logistic regression. The OPPERA findings provided evidence supporting previously reported associations between TMD and 2 genes: HTR2A and COMT. Other genes were revealed as potential new genetic risk factors for TMD, including NR3C1, CAMK4, CHRM2, IFRD1, and GRK5. While these findings need to be replicated in independent cohorts, the genes potentially represent important markers of risk for TMD, and they identify potential targets for therapeutic intervention. Perspective Genetic risk factors for TMD pain were explored in the case-control component of the OPPERA cooperative agreement, a large population-based prospective cohort study. Over 350 candidate pain genes were assessed using a candidate gene panel, with several genes displaying preliminary evidence for association with TMD status.