The journal of pain : official journal of the American Pain Society
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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. ⋯ 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.
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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. ⋯ 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.
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Many studies report that people with temporomandibular disorders (TMD) are more sensitive to experimental pain stimuli than TMD-free controls. Such differences in sensitivity are observed in remote body sites as well as in the orofacial region, suggesting a generalized upregulation of nociceptive processing in TMD cases. This large case-control study of 185 adults with TMD and 1,633 TMD-free controls measured sensitivity to painful pressure, mechanical cutaneous, and heat stimuli, using multiple testing protocols. Based on an unprecedented 36 experimental pain measures, 28 showed statistically significantly greater pain sensitivity in TMD cases than controls. The largest effects were seen for pressure pain thresholds at multiple body sites and cutaneous mechanical pain threshold. The other mechanical cutaneous pain measures and many of the heat pain measures showed significant differences, but with lesser effect sizes. Principal component analysis (PCA) of the pain measures derived from 1,633 controls identified 5 components labeled: 1) heat pain ratings; 2) heat pain aftersensations and tolerance; 3) mechanical cutaneous pain sensitivity; 4) pressure pain thresholds; and 5) heat pain temporal summation. These results demonstrate that compared to TMD-free controls, chronic TMD cases are more sensitive to many experimental noxious stimuli at extracranial body sites, and provide for the first time the ability to directly compare the case-control effect sizes of a wide range of pain sensitivity measures. ⋯ This article describes experimental pain sensitivity differences between a large sample of people with chronic TMD and non-TMD controls, using multiple stimulus modalities and measures. Variability in the magnitude and consistency of case-control differences highlight the need to consider multiple testing measures to adequately assess pain processing alterations in chronic pain conditions.