COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain

When measured once, psychological stress predicts development of painful temporomandibular disorder (TMD). However, a single measurement fails to characterize the dynamic nature of stress over time. Moreover, effects of stress on pain likely vary according to biological susceptibility. We hypothesized that temporal escalation in stress exacerbates risk for TMD, and the effect is amplified by allelic variants in a gene, catechol-O-methyltransferase (COMT), regulating catechol neurotransmitter catabolism. We used data from the Orofacial Pain: Prospective Evaluation and Risk Assessment prospective cohort study of 2,707 community-dwelling adults with no lifetime history of TMD on enrollment. At baseline and quarterly periods thereafter, the Perceived Stress Scale (PSS) measured psychological stress. Genotyped DNA from blood samples determined COMT diplotypes. During follow-up of 0.25 to 5.2 y, 248 adults developed examiner-verified incident TMD. PSS scores at baseline were 20% greater (P < 0.001) in adults who developed incident TMD compared with TMD-free controls. Baseline PSS scores increased by 9% (P = 0.003) during follow-up in cases but remained stable in controls. This stress escalation was limited to incident cases with COMT diplotypes coding for low-activity COMT, signifying impaired catabolism of catecholamines. Cox regression models confirmed significant effects on TMD hazard of both baseline PSS (P < 0.001), modeled as a time-constant covariate, and change in PSS (P < 0.001), modeled as a time-varying covariate. Furthermore, a significant (P = 0.04) interaction of COMT diplotype and time-varying stress showed that a postbaseline increase of 1.0 standard deviation in PSS more than doubled risk of TMD incidence in subjects with low-activity COMT diplotypes (hazard ratio = 2.35; 95% confidence limits: 1.66, 3.32), an effect not found in subjects with high-activity COMT diplotypes (hazard ratio = 1.42; 95% confidence limits: 0.96, 2.09). Findings provide novel insights into dynamic effects of psychological stress on TMD pain, highlighting that effects are most pronounced in individuals whose genetic susceptibility increases responsiveness to catecholamine neurotransmitters

Characteristics Associated With High-Impact Pain in People With Temporomandibular Disorder: A Cross-Sectional Study

High-impact (disabling) pain diminishes the quality of life and increases health care costs. The purpose of this study was to identify the variables that distinguish between high- and low-impact pain among individuals with painful temporomandibular disorder (TMD). Community-dwelling adults (N = 846) with chronic TMD completed standardized questionnaires that assessed the following: 1) sociodemographic characteristics, 2) psychological distress, 3) clinical pain, and 4) experimental pain. We used high-impact pain, classified using the Graded Chronic Pain Scale, as the dependent variable in logistic regression modeling to evaluate the contribution of variables from each domain. Cross-validated area under the receiver operating characteristic curve (AUC) quantified model discrimination. One-third of the participants had high-impact pain. Sociodemographic variables discriminated weakly between low- and high-impact pain (AUC =.61, 95% confidence interval [CI] = 0.57, 0.65), with the exception of race. An 18-variable model encompassing all 4 domains had good discrimination (AUC = 0.79, 95% CI = 0.75, 0.82), as did a simplified model (sociodemographic variables plus catastrophizing, jaw limitation, and number of painful body sites) (AUC = 0.79, 95% CI = 0.76, 0.82). Duration of pain, sex, and experimental pain testing results were not associated. The characteristics that discriminated most effectively between people with low- and high-impact TMD pain included clinical pain features and the ability to cope with pain. Perspective: This article presents the results of a multivariable model designed to discriminate between people with high- and low-impact pain in a community-based sample of people with painful chronic TMD. The findings emphasize the importance of catastrophizing, jaw limitation, and painful body sites associated with pain-related impact

Sleep Apnea Symptoms and Risk of Temporomandibular Disorder: OPPERA Cohort

The authors tested the hypothesis that obstructive sleep apnea (OSA) signs/symptoms are associated with the occurrence of temporomandibular disorder (TMD), using the OPPERA prospective cohort study of adults aged 18 to 44 years at enrollment (n = 2,604) and the OPPERA case-control study of chronic TMD (n = 1,716). In both the OPPERA cohort and case-control studies, TMD was examiner determined according to established research diagnostic criteria. People were considered to have high likelihood of OSA if they reported a history of sleep apnea or ≥ 2 hallmarks of OSA: loud snoring, daytime sleepiness, witnessed apnea, and hypertension. Cox proportional hazards regression estimated hazard ratios (HRs) and 95% confidence limits (CL) for first-onset TMD. Logistic regression estimated odds ratios (OR) and 95% CL for chronic TMD. In the cohort, 248 individuals developed first-onset TMD during the median 2.8-year follow-up. High likelihood of OSA was associated with greater incidence of first-onset TMD (adjusted HR = 1.73; 95% CL, 1.14, 2.62). In the case-control study, high likelihood of OSA was associated with higher odds of chronic TMD (adjusted OR = 3.63; 95% CL, 2.03, 6.52). Both studies supported a significant association of OSA symptoms and TMD, with prospective cohort evidence finding that OSA symptoms preceded first-onset TMD

Effect of age, sex and gender on pain sensitivity: A narrative review

© 2017 Eltumi And Tashani. Introduction: An increasing body of literature on sex and gender differences in pain sensitivity has been accumulated in recent years. There is also evidence from epidemiological research that painful conditions are more prevalent in older people. The aim of this narrative review is to critically appraise the relevant literature investigating the presence of age and sex differences in clinical and experimental pain conditions. Methods: A scoping search of the literature identifying relevant peer reviewed articles was conducted on May 2016. Information and evidence from the key articles were narratively described and data was quantitatively synthesised to identify gaps of knowledge in the research literature concerning age and sex differences in pain responses. Results: This critical appraisal of the literature suggests that the results of the experimental and clinical studies regarding age and sex differences in pain contain some contradictions as far as age differences in pain are concerned. While data from the clinical studies are more consistent and seem to point towards the fact that chronic pain prevalence increases in the elderly findings from the experimental studies on the other hand were inconsistent, with pain threshold increasing with age in some studies and decreasing with age in others. Conclusion: There is a need for further research using the latest advanced quantitative sensory testing protocols to measure the function of small nerve fibres that are involved in nociception and pain sensitivity across the human life span. Implications: Findings from these studies should feed into and inform evidence emerging from other types of studies (e.g. brain imaging technique and psychometrics) suggesting that pain in the older humans may have unique characteristics that affect how old patients respond to intervention

An experimental investigation of the effect of age and sex/gender on pain sensitivity in healthy human participants

© 2018 El-Tumi et al. Background: Ageing is associated with alterations of the structure and function of somatosensory tissue that can impact on pain perception. The aim of this study was to investigate the relationship between age and pain sensitivity responses to noxious thermal and mechanical stimuli in healthy adults. Methods: 56 unpaid volunteers (28 women) aged between 20 and 55 years were categorised according to age into one of seven possible groups. The following measurements were taken: thermal detection thresholds, heat pain threshold and tolerance using a TSA-II NeuroSensory Analyzer; pressure pain threshold using a handheld electronic pressure algometer; and cold pressor pain threshold, tolerance, intensity and unpleasantness. Results: There was a positive correlation between heat pain tolerance and age (r = 0.228, P = 0.046), but no statistically significant differences between age groups for cold or warm detection thresholds, or heat pain threshold or tolerance. Forward regression found increasing age to be a predictor of increased pressure pain threshold (B = 0.378, P = 0.002), and sex/gender to be a predictor of cold pressor pain tolerance, with women having lower tolerance than men (B =-0.332, P = 0.006). Conclusion: The findings of this experimental study provide further evidence that pressure pain threshold increases with age and that women have lower thresholds and tolerances to innocuous and noxious thermal stimuli. Significance: The findings demonstrate that variations in pain sensitivity response to experimental stimuli in adults vary according to stimulus modality, age and sex and gender

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd