Search

Aims To determine the relationship between hormonal contraceptive (HC) use and painful symptoms, particularly those associated with headache and painful temporomandibular disorders (TMD). Methods Data from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort study were used. During the 2.5-year median follow-up period, quarterly health update (QHU) questionnaires were completed by 1,475 women aged 18 to 44 years who did not have TMD, menopause, hysterectomy, or hormone replacement therapy use at baseline. QHU questionnaires evaluated HC use, symptoms of headache and TMD, and pain of ≥ 1 day duration in 12 body regions. Participants who developed TMD symptoms were examined to classify clinical TMD. Headache symptoms were classified based on the International Classification of Headache Disorders 3 (ICHD-3). Associations between HC use and pain symptoms were analyzed using generalized estimating equations and Cox models. Results HC use, endorsed in 33.7% of QHU questionnaires, was significantly associated with concurrent symptoms of TMD (odds ratio [OR]: 1.20, 95% CI: 1.06 to 1.35) and headache (OR: 1.26, 95% CI: 1.11 to 1.43). HC use was also significantly associated with concurrent pain of ≥ 1 day duration in the head (OR: 1.38, 95% CI: 1.16 to 1.63), face (OR: 1.44, 95% CI: 1.13 to 1.83), and legs (OR: 1.22, 95% CI: 1.01 to 1.47), but not elsewhere. Initiation of HC use was associated with increased odds of subsequent TMD symptoms (OR: 1.37, 95% CI: 1.13 to 1.66) and pain of ≥ 1 day in the head (OR: 1.37, 95% CI: 1.01 to 1.85). Discontinuing HC use was associated with lower odds of subsequent headache (OR: 0.82, 95% CI: 0.67 to 0.99). HC use was not significantly associated with subsequent onset of examiner-classified TMD. Conclusion These findings imply that HC influences craniofacial pain, and that this pain diminishes after cessation of HC use.

Propranolol is a nonselective beta-adrenergic receptor antagonist. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b trial enrolled participants aged 18 to 65 years with temporomandibular disorder myalgia to evaluate efficacy and safety of propranolol compared with placebo in reducing facial pain. Participants were randomized 1:1 to either extended-release propranolol hydrochloride (60 mg, BID) or placebo. The primary endpoint was change in facial pain index (FPI = facial pain intensity multiplied by facial pain duration, divided by 100). Efficacy was analyzed as a mean change in FPI from randomization to week 9 and as the proportion of participants with ≥30% or ≥50% reductions in FPI at week 9. Regression models tested for treatment-group differences adjusting for study site, sex, race, and FPI at randomization. Of 299 participants screened, 200 were randomized; 199 had at least one postrandomization FPI measurement and were included in intention-to-treat analysis. At week 9, model-adjusted reductions in mean FPI did not differ significantly between treatment groups (-1.8, 95% CL: -6.2, 2.6; P = 0.41). However, the proportion with a ≥30% reduction in FPI was significantly greater for propranolol (69.0%) than placebo (52.6%), and the associated number-needed-to-treat was 6.1 (P = 0.03). Propranolol was likewise efficacious for a ≥50% reduction in FPI (number-needed-to-treat = 6.1, P = 0.03). Adverse event rates were similar between treatment groups, except for more frequent fatigue, dizziness, and sleep disorder in the propranolol group. Propranolol was not different from placebo in reducing mean FPI but was efficacious in achieving ≥30% and ≥50% FPI reductions after 9 weeks of treatment among temporomandibular disorder participants.

BACKGROUND. Patients often seek consultation with dentists for temporomandibular disorders (TMDs). The objectives of this article were to describe the methods of a large prospective cohort study of painful TMD management, practitioners’ and patients’ characteristics, and practitioners’ initial treatment recommendations conducted by The National Dental Practice-Based Research Network (the “network”). METHODS. Participating dentists recruited into this study treated patients seeking treatment for painful TMDs. The authors developed self-report instruments based on well-accepted instruments. The authors collected demographics, biopsychosocial characteristics, TMD symptoms, diagnoses, treatments, treatment adherence, and painful TMDs and jaw function outcomes through 6 months. RESULTS. Participating dentists were predominately White (76.8%) and male (62.2%), had a mean age of 52 years, and were general practitioners (73.5%) with 23.8% having completed an orofacial pain residency. Of the 1,901 patients with painful TMDs recruited, the predominant demographics were White (84.3%) and female (83.3%). Patients’ mean age was 44 years, 88.8% self-reported good to excellent health, and 85.9% had education beyond high school. Eighty-two percent had pain or stiffness of the jaw on awakening, and 40.3% had low-intensity pain. The most frequent diagnoses were myalgia (72.4%) and headache attributed to TMDs (51.0%). Self-care instruction (89.4%), intraoral appliances (75.4%), and medications (57.6%) were recommended frequently. CONCLUSIONS. The characteristics of this TMD cohort include those typical of US patients with painful TMDs. Network practitioners typically managed TMDs using conservative treatments. PRACTICAL IMPLICATIONS. This study provides credible data regarding painful TMDs and TMD management provided by network practitioners across the United States. Knowledge acquired of treatment recommendations and patient reports may support future research and improve dental school curricula.

Cross-sectional studies confirm, as expected, a positive association between jaw injury and painful temporomandibular disorders (TMDs), but prospective evaluations are lacking. We prospectively assessed incident jaw injury, injury type, and development of TMD in adults aged 18 to 44 years. Data were collected from 3258 individuals from communities surrounding 4 US academic institutes between 2006 and 2008. At enrollment, participants reported no TMD history and no facial injuries in the previous 6 months. Quarterly, follow-up questionnaires assessed incident jaw injury, which was classified as intrinsic (attributed to yawning or prolonged mouth opening) or extrinsic (attributed to other causes). Examiners classified incident TMD during a median follow-up period of 2.8 years (range 0.2-5.2 years). Cox regression models used jaw injury as a time-dependent covariate to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with incident TMD. Among 1729 participants with complete data, 175 developed TMD. Eighty percent of injuries were intrinsic. Temporomandibular disorder annual incidence was nearly twice as high in those experiencing jaw injury (5.37%) compared with those who did not (3.44%). In the Cox model that accounted for timing of injury, the corresponding HR was 3.94 (95% CI = 2.82-5.50) after adjusting for study site, age, race, and sex. Hazard ratios did not differ (P = 0.91) for extrinsic injuries (HR = 4.03, 95% CI = 2.00-8.12) and intrinsic injuries (HR = 3.85, 95% CI = 2.70-5.49). Jaw injury was strongly associated with incident TMD. If surveillance and intervention after jaw injury is to be effective in preventing TMD, they should focus on both intrinsic and extrinsic injuries.

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.

Aims To investigate the associations between temporomandibular disorders (TMDs) and sleep disorders in adult subjects. Methods The PubMed, Embase, Evidence-Based Medicine Reviews, and ProQuest Dissertations & Theses databases were searched for studies published in English up to September 2019. Unpublished/gray literature and reference lists of identified articles were also examined. Inclusion criteria were male and female adults, presence or absence of a TMD based on the RDC/TMD or DC/TMD criteria, presence or absence of a sleep disorder according to the International Classification of Sleep Disorders, and any of the following study designs: cross-sectional, case-control, or longitudinal. Methodologic quality assessment was conducted using the National Heart, Lung, and Blood Institute quality assessment tools. Results Twenty-two studies (11 cross-sectional, 9 case-control, 1 prospective cohort, and 1 mixed design) met the inclusion criteria. TMDs were assessed independently in relation to sleep bruxism (SB), obstructive sleep apnea (OSA), and sleep quality (SQ). All studies but one assessed TMDs using the RDC/TMD criteria. The relation between the TMD and the different sleep disorders was conflicting for SB and positive for OSA and SQ. Five studies were of good quality, and 17 were of fair quality. Conclusions The evidence is inconclusive regarding the relationship between TMDs and SB and insufficient regarding the relationship with OSA. There is consistently fair evidence to support an association between TMD and SQ. This study highlights the need for higher-quality longitudinal studies to clarify the association between TMDs and sleep disorders.

Introduction The migraine-preventive drug propranolol is efficacious in reducing pain from temporomandibular disorder, suggesting potential modifying or mediating effects of comorbid migraine. Methods In this randomized controlled trial, myofascial temporomandibular disorder patients were treated with propranolol or placebo for 9 weeks. The primary endpoint was change in a facial pain index derived from daily symptom diaries. Linear and logistic regression models tested for a migraine × treatment-group interaction in reducing facial pain index. Counterfactual models explored changes in headache impact and heart rate as mediators of propranolol's efficacy. Results Propranolol's efficacy in reducing facial pain index was greater among the 104 migraineurs than the 95 non-migraineurs: For example, for the binary ≥ 30% reduction in facial pain index, odds ratios were 3.3 (95% confidence limits: 1.4, 8.1) versus 1.3 (0.5, 3.2), respectively, although the interaction was statistically non-significant ( p = 0.139). Cumulative response curves confirmed greater efficacy for migraineurs than non-migraineurs (differences in area under the curve 26% and 6%, respectively; p = 0.081). While 9% of the treatment effect was mediated by reduced headache impact, 46% was mediated by reduced heart rate. Conclusions Propranolol was more efficacious in reducing temporomandibular disorder pain among migraineurs than non-migraineurs, with more of the effect mediated by reduced heart rate than by reduced headache impact. Study identification and registration SOPPRANO; NCT02437383; https://clinicaltrials.gov/ct2/show/NCT02437383

Pain-related disability is a multifaceted construct that refers to the impact of pain on an individual's capacity to fulfill their self-defined and social roles. This research examined the relationship between clinical, psychological, and pain sensitivity factors and pain-related disability among adults with chronic temporomandibular disorder (TMD). We analyzed data from a cross-sectional community-based sample of 1088 men and women with chronic TMD. We first constructed and tested a measure of pain-related disability (ie, pain impact), including a variable assessing presenteeism, created measurement models of jaw limitation, psychological unease (negative affect, somatic symptoms, and catastrophizing), and experimental pain sensitivity (eg, pressure pain threshold, thermal tolerance, and mechanical pressure pain threshold). Subsequently, latent variables were combined in a structural equation model. Participants (n = 1088) were 18 to 44 years old (mean 29.2, SD ± 7.8) whose chronic TMD had persisted, on average, for 6.9 years (SD ± 6.4). A model of pain-related disability, jaw limitation, and psychological unease was created and refined with exploratory model revisions to account for correlation among variables. Estimation of the final model indicated excellent fit with the data (root-mean-square error of approximation = 0.048, root-mean-square error of approximation 90% confidence interval [CI] 0.043-0.053, comparative fit index = 0.956, standardized root-mean-square residual = 0.040). Jaw functional limitation and psychological unease was strongly related to pain-related disability. Experimental pain sensitivity was removed from our model because of weak direct effect and the burden of performing experimental pain sensitivity testing in a clinical setting. The final model explained 78% of the variance in pain-related disability.

The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR and its natural ligand, epiregulin (EREG), in pain processing. We show that inhibition of EGFR with clinically available compounds strongly reduced nocifensive behavior in mouse models of inflammatory and chronic pain. EREG-mediated activation of EGFR enhanced nociception through a mechanism involving the PI3K/AKT/mTOR pathway and matrix metalloproteinase-9. Moreover, EREG application potentiated capsaicin-induced calcium influx in a subset of sensory neurons. Both the EGFR and EREG genes displayed a genetic association with the development of chronic pain in several clinical cohorts of temporomandibular disorder. Thus, EGFR and EREG may be suitable therapeutic targets for persistent pain conditions.

Temporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. We conducted a discovery genome-wide association study (GWAS) of TMD in 10,153 participants (769 cases, 9,384 controls) of the US Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The most promising single-nucleotide polymorphisms (SNPs) were tested in meta-analysis of 4 independent cohorts. One replication cohort was from the United States, and the others were from Germany, Finland, and Brazil, totaling 1,911 TMD cases and 6,903 controls. A locus near the sarcoglycan alpha ( SGCA), rs4794106, was suggestive in the discovery analysis ( P = 2.6 × 106) and replicated (i.e., 1-tailed P = 0.016) in the Brazilian cohort. In the discovery cohort, sex-stratified analysis identified 2 additional genome-wide significant loci in females. One lying upstream of the relaxin/insulin-like family peptide receptor 2 ( RXP2) (chromosome 13, rs60249166, odds ratio [OR] = 0.65, P = 3.6 × 10−8) was replicated among females in the meta-analysis (1-tailed P = 0.052). The other (chromosome 17, rs1531554, OR = 0.68, P = 2.9 × 10−8) was replicated among females (1-tailed P = 0.002), as well as replicated in meta-analysis of both sexes (1-tailed P = 0.021). A novel locus at genome-wide level of significance (rs73460075, OR = 0.56, P = 3.8 × 10−8) in the intron of the dystrophin gene DMD (X chromosome), and a suggestive locus on chromosome 7 (rs73271865, P = 2.9 × 10−7) upstream of the Sp4 Transcription Factor ( SP4) gene were identified in the discovery cohort, but neither of these was replicated. The SGCA gene encodes SGCA, which is involved in the cellular structure of muscle fibers and, along with DMD, forms part of the dystrophin-glycoprotein complex. Functional annotation suggested that several of these variants reside in loci that regulate processes relevant to TMD pathobiologic processes.

There is good evidence that poor sleep quality increases risk of painful temporomandibular disorder (TMD). However, little is known about the course of sleep quality in the months preceding TMD onset, and whether the relationship is mediated by heightened sensitivity to pain. The Pittsburgh Sleep Quality Index was administered at enrollment into the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort study. Thereafter the Sleep Quality Numeric Rating Scale was administered every 3 months to 2,453 participants. Sensitivity to experimental pressure pain and pinprick pain stimuli was measured at baseline and repeated during follow-up of incident TMD cases (n = 220) and matched TMD-free controls (n = 193). Subjective sleep quality deteriorated progressively, but only in those who subsequently developed TMD. A Cox proportional hazards model showed that risk of TMD was greater among participants whose sleep quality worsened during follow-up (adjusted hazard ratio = 1.73, 95% confidence limits = 1.29, 2.32). This association was independent of baseline measures of sleep quality, psychological stress, somatic awareness, comorbid conditions, nonpain facial symptoms, and demographic characteristics. Poor baseline sleep quality was not significantly associated with baseline pain sensitivity or with subsequent change in pain sensitivity. Furthermore the relationship between sleep quality and TMD incidence was not mediated via baseline pain sensitivity or change in pain sensitivity. Perspective Subjective sleep quality deteriorates progressively before the onset of painful TMD, but sensitivity to experimental pain does not mediate this relationship. Furthermore, the relationship is independent of potential confounders such as psychological stress, somatic awareness, comorbid conditions, nonpain facial symptoms, and various demographic factors.

Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants affect enzymatic activity and pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its association with pain phenotypes are not always replicated. Here, we investigated if interactions among functional COMT haplotypes, stress, and sex can modify the effect of COMT genetic variants on pain sensitivity. We tested these interactions in a cross-sectional study, including 2 cohorts, one of 2972 subjects tested for thermal pain sensitivity (Orofacial Pain: Prospective Evaluation and Risk Assessment) and one of 948 subjects with clinical acute pain after motor vehicle collision (post-motor vehicle collision). In both cohorts, the COMT high-pain sensitivity (HPS) haplotype showed robust interaction with stress and number of copies of the HPS haplotype was positively associated with pain sensitivity in nonstressed individuals, but not in stressed individuals. In the post-motor vehicle collision cohort, there was additional modification by sex: the HPS-stress interaction was apparent in males, but not in females. In summary, our findings indicate that stress and sex should be evaluated in association studies aiming to investigate the effect of COMT genetic variants on pain sensitivity.

BACKGROUND Oral behaviors (OBs) must be assessed as part of a biobehavioural evaluation for patients with temporomandibular disorders (TMD). OBJECTIVES The aims of this study were: to translate and culturally adapt the Oral Behaviors Checklist (OBC) into Portuguese; to evaluate its basic psychometric properties; and to assess the utility of the Portuguese OBC. METHODS The Portuguese translation, cross-cultural equivalence, and two studies (Pre-field test, N = 8, and field test, N = 45) of the OBC adhered to official guidelines of the International RDC/TMD Research Consortium (now, INfORM). In the formal test (N = 120) the Portuguese RDC/TMD was used for TMD diagnosis. RESULTS Translation and cultural equivalence of the OBC into Portuguese was reviewed and approved by an expert panel. In the field test, item agreement between English and Portuguese OBC versions was very good (weighted Kappa ≥ 0.934). Test-retest reliability of the OBCSumScore was excellent intra-class correlation coefficient ((ICC) = 0.998, P

AIM To develop and preliminarily evaluate a new screening instrument for atypical odontalgia (AO) or persistent dentoalveolar pain disorder (PDAP). To evaluate the instrument's performance in detecting AO/PDAP amongst a heterogeneous group of orofacial pain conditions and pain-free controls and empirically compare its performance with an established neuropathic screening instrument (S-LANSS), which is the best available standard. METHODS The study design was cross-sectional; subjects recruited included a convenience sample of pain-free controls (n = 21) and four groups of orofacial pain conditions: AO/PDAP (n = 22); trigeminal neuralgia (n = 21); temporomandibular disorder (n = 41); and acute dental pain (n = 41). The instrument's internal reliability and factor structure were examined alongside its sensitivity and specificity and ROC-determined threshold score. RESULTS The 9 AO/PDAP-specific items were found to moderately correlate with the S-LANSS (r = 0.58; P

Supplemental Digital Content is Available in the Text. A catechol-O-methyltransferase genetic marker of pain led to the discovery of an alternative enzyme that acts through dopamine rather than epinephrine, characteristic of reference catechol-O-methyltransferase., Catechol-O-methyltransferase (COMT) metabolizes catecholaminergic neurotransmitters. Numerous studies have linked COMT to pivotal brain functions such as mood, cognition, response to stress, and pain. Both nociception and risk of clinical pain have been associated with COMT genetic variants, and this association was shown to be mediated through adrenergic pathways. Here, we show that association studies between COMT polymorphic markers and pain phenotypes in 2 independent cohorts identified a functional marker, rs165774, situated in the 3′ untranslated region of a newfound splice variant, (a)-COMT. Sequence comparisons showed that the (a)-COMT transcript is highly conserved in primates, and deep sequencing data demonstrated that (a)-COMT is expressed across several human tissues, including the brain. In silico analyses showed that the (a)-COMT enzyme features a distinct C-terminus structure, capable of stabilizing substrates in its active site. In vitro experiments demonstrated not only that (a)-COMT is catalytically active but also that it displays unique substrate specificity, exhibiting enzymatic activity with dopamine but not epinephrine. They also established that the pain-protective A allele of rs165774 coincides with lower COMT activity, suggesting contribution to decreased pain sensitivity through increased dopaminergic rather than decreased adrenergic tone, characteristic of reference isoforms. Our results provide evidence for an essential role of the (a)-COMT isoform in nociceptive signaling and suggest that genetic variations in (a)-COMT isoforms may contribute to individual variability in pain phenotypes.

Evidence on cultural differences in prevalence and impact of common chronic pain conditions, comparing individuals with temporomandibular disorders (TMD) versus individuals without TMD, is limited. The aim was to assess cross-cultural comorbid pain conditions in women with chronic TMD pain. Consecutive women patients (n = 122) with the index condition of chronic TMD pain diagnosed per the research diagnostic criteria for TMD and TMD-free controls (n = 121) matched for age were recruited in Saudi Arabia, Italy and Sweden. Self-report questionnaires assessed back, chest, stomach and head pain for prevalence, pain intensity and interference with daily activities. Logistic regression was used for binary variables, and ancova was used for parametric data analysis, adjusting for age and education. Back pain was the only comorbid condition with a different prevalence across cultures; Swedes reported a lower prevalence compared to Saudis (P < 0·01). Saudis reported higher prevalence of work reduced >50% due to back pain compared to Italians or Swedes (P < 0·01). Headache was the most common comorbid condition in all three cultures. The total number of comorbid conditions did not differ cross-culturally but were reported more by TMD-pain cases than TMD-free controls (P < 0·01). For both back and head pain, higher average pain intensities (P < 0·01) and interference with daily activities (P < 0·01) were reported by TMD-pain cases, compared to TMD-free controls. Among TMD-pain cases, Italians reported the highest pain-related disability (P < 0·01). Culture influences the associated comorbidity of common pain conditions. The cultural influence on pain expression is reflected in different patterns of physical representation.

There is a need to expand the current temporomandibular disorders' (TMDs) classification to include less common but clinically important disorders. The immediate aim was to develop a consensus-based classification system and associated diagnostic criteria that have clinical and research utility for less common TMDs. The long-term aim was to establish a foundation, vis-à-vis this classification system, that will stimulate data collection, validity testing and further criteria refinement. A working group [members of the International RDC/TMD Consortium Network of the International Association for Dental Research (IADR), members of the Orofacial Pain Special Interest Group (SIG) of the International Association for the Study of Pain (IASP), and members from other professional societies] reviewed disorders for inclusion based on clinical significance, the availability of plausible diagnostic criteria and the ability to operationalise and study the criteria. The disorders were derived from the literature when possible and based on expert opinion as necessary. The expanded TMDs taxonomy was presented for feedback at international meetings. Of 56 disorders considered, 37 were included in the expanded taxonomy and were placed into the following four categories: temporomandibular joint disorders, masticatory muscle disorders, headache disorders and disorders affecting associated structures. Those excluded were extremely uncommon, lacking operationalised diagnostic criteria, not clearly related to TMDs, or not sufficiently distinct from disorders already included within the taxonomy. The expanded TMDs taxonomy offers an integrated approach to clinical diagnosis and provides a framework for further research to operationalise and test the proposed taxonomy and diagnostic criteria.

We explored causal mediation of sleep quality and perceived stress in development of painful temporomandibular disorder (TMD). Sleep quality and perceived stress were assessed at baseline and quarterly intervals thereafter in 2,737 initially TMD-free adults in the Orofacial Pain Prospective Evaluation and Risk Assessment study (OPPERA) prospective cohort study. During follow-up, incident TMD cases were classified using research diagnostic criteria. Mediation analysis was conducted using a weighted Cox proportional hazards regression model that estimated hazard ratios (HRs) and 95% confidence limits (CL) of first-onset TMD. Models determined whether: 1) poor sleep quality during follow-up mediated the effect of baseline perceived stress on first-onset TMD, and 2) perceived stress during follow-up mediated the effect of baseline poor sleep quality on first-onset TMD. In both analyses, the total effect was decomposed into natural direct and indirect effects. Poor baseline sleep quality led to heightened perceived stress that then contributed to TMD development. When the total effect of poor sleep quality (HR = 2.10, CL = 1.76, 2.50) was decomposed, 34% of its effect was mediated by perceived stress (indirect effect HR = 1.29, CL = 1.06, 1.58). The effect of perceived stress on first-onset TMD was not mediated by sleep quality. Improving sleep may avert escalation of stress, limiting effects of both factors on TMD development. Perspective Causal mediation analysis highlights mechanisms by which poor sleep quality promotes development of TMD. First, poor sleep quality exerts a direct effect on pain. Second, it triggers a heightened perception of stress, which acts as an intermediate factor in the causal pathway between poor sleep quality and first-onset TMD pain.

While cross-sectional studies have demonstrated an association between headache and temporomandibular disorder (TMD), whether headache can predict the onset of TMD is unknown. The aims of this study were to evaluate the contribution of headache to the risk of developing TMD and describe patterns of change in headache types over time. An initially TMD-free cohort of 2410 persons with low frequency of headache completed quarterly questionnaires assessing TMD and headache symptoms over a median 3.0-year follow-up period. First-onset TMD was confirmed by clinical examination in 199 participants. Baseline reports of migraine (hazard ratio [HR] = 1.67, 95% confidence interval [CI]: 1.06-2.62) or mixed headache types (HR = 4.11, 95% CI: 1.47-11.46), or headache frequency (HR = 2.13, 95% CI: 1.31-3.48) predicted increased risk of developing TMD. In addition, headache dynamics across the follow-up period before the TMD onset were evaluated in a nested case-control study where 248 incident TMD cases were matched to 191 TMD-free controls. Both headache prevalence and frequency increased across the observation period among those who developed TMD but not among controls. Patients with TMD were more likely to experience worsening in the headache type compared with that by controls, eg, prevalence of definite migraine among TMD cases increased 10-fold. Among all headache types experienced by patients with TMD before the TMD onset, migraine had the highest odds of progression relative to remission (odds ratio = 2.8, 95% CI: 1.6-4.8), whereas for controls this ratio was significant only for the tension-type headache (odds ratio = 2.1, 95% CI: 1.2-3.9). The important clinical implication of these findings is that adequate treatment of migraine may reduce the risk for developing TMD.

This study evaluated the contributions of psychological status and cardiovascular responsiveness to racial/ethnic differences in experimental pain sensitivity. The baseline measures of 3,159 healthy individuals-non-Hispanic white (NHW): 1,637, African-American (AA): 1,012, Asian: 299, and Hispanic: 211-from the OPPERA prospective cohort study were used. Cardiovascular responsiveness measures and psychological status were included in structural equation modeling based mediation analyses. Pain catastrophizing was a significant mediator for the associations between race/ethnicity and heat pain tolerance, heat pain ratings, heat pain aftersensations, mechanical cutaneous pain ratings and aftersensations, and mechanical cutaneous pain temporal summation for both Asians and AAs compared to NHWs. HR/MAP index showed a significant inconsistent (mitigating) mediating effect on the association between race/ethnicity (AAs vs. NHWs) and heat pain tolerance. Similarly, coping inconsistently mediated the association between race/ethnicity and mechanical cutaneous pain temporal summation in both AAs and Asians, compared to NHWs. The factor encompassing depression, anxiety, and stress was a significant mediator for the associations between race/ethnicity (Asians vs. NHWs) and heat pain aftersensations. Thus, while pain catastrophizing mediated racial/ethnic differences in many of the QST measures, the psychological and cardiovascular mediators were distinctly restrictive, signifying multiple independent mechanisms in racial/ethnic differences in pain.

Case-control studies have documented clinical manifestations of chronic temporomandibular disorder (TMD), whereas clinical predictors of TMD development are largely unknown. We evaluated 41 clinical orofacial characteristics thought to predict first-onset TMD in a prospective cohort study of U.S. adults aged 18 to 44 years. During the median 2.8-year follow-up period, 2,737 people completed quarterly screening questionnaires. Those reporting symptoms were examined and 260 people were identified with first-onset TMD. Univariate and multivariable Cox regression models quantified associations between baseline clinical orofacial measures and TMD incidence. Significant predictors from baseline self-report instruments included oral parafunctions, prior facial pain and its life-impact, temporomandibular joint noises and jaw locking, and nonspecific orofacial symptoms. Significant predictors from the baseline clinical examination were pain on jaw opening and pain from palpation of masticatory, neck, and body muscles. Examiner assessments of temporomandibular joint noise and tooth wear facets did not predict incidence. In multivariable analysis, nonspecific orofacial symptoms, pain from jaw opening, and oral parafunctions predicted TMD incidence. The results indicate that only a few orofacial examination findings influenced TMD incidence, and only to a modest degree. More pronounced influences were found for self-reported symptoms, particularly those that appeared to reflect alterations to systems beyond the masticatory tissues. Perspective OPPERA's prospective cohort study identifies predictors of first-onset TMD comprising self-reported orofacial symptoms and examination findings. The results suggest a complex pattern of TMD etiology that is influenced by disorders locally, in masticatory tissues, and systemically, in pain-regulatory systems.

Case-control studies have consistently associated psychological factors with chronic pain in general and with temporomandibular disorder (TMD) specifically. However, only a handful of prospective studies have explored whether preexisting psychological characteristics represent risk factors for first-onset TMD. The current findings derive from the prospective cohort study of the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) cooperative agreement. For this study, 3,263 TMD-free participants completed a battery of psychological instruments assessing general psychological adjustment and personality, affective distress, psychosocial stress, somatic symptoms, and pain coping and catastrophizing. Study participants were then followed prospectively for an average of 2.8 years to ascertain cases of first-onset of TMD, and 2,737 provided follow-up data and were considered in the analyses of TMD onset. In bivariate and demographically adjusted analyses, several psychological variables predicted increased risk of first-onset TMD, including reported somatic symptoms, psychosocial stress, and affective distress. Principal component analysis of 26 psychological scores was used to identify latent constructs, revealing 4 components: stress and negative affectivity, global psychological and somatic symptoms, passive pain coping, and active pain coping. In multivariable analyses, global psychological and somatic symptoms emerged as the most robust risk factor for incident TMD. These findings provide evidence that measures of psychological functioning can predict first onset of TMD. Future analyses in the OPPERA cohort will determine whether these psychological factors interact with other variables to increase risk for TMD onset and persistence. Perspective This article reports that several premorbid psychological variables predict first-onset TMD in the OPPERA study, a large prospective cohort study designed to discover causal determinants of TMD pain. Measures of somatic symptoms were most strongly associated with TMD onset, but perceived stress, previous life events, and negative affect also predicted TMD incidence.

Human association studies of common genetic polymorphisms have identified many loci that are associated with risk of complex diseases, although individual loci typically have small effects. However, by envisaging genetic associations in terms of cellular pathways, rather than any specific polymorphism, combined effects of many biologically relevant alleles can be detected. The effects are likely to be most apparent in investigations of phenotypically homogenous subtypes of complex diseases. We report findings from a case-control, genetic association study of relationships between 2925 single nucleotide polymorphisms (SNPs) and 2 subtypes of a commonly occurring chronic facial pain condition, temporomandibular disorder (TMD): 1) localized TMD and 2) TMD with widespread pain. When compared to healthy controls, cases with localized TMD differed in allelic frequency of SNPs that mapped to a serotonergic receptor pathway (P=0.0012), while cases of TMD with widespread pain differed in allelic frequency of SNPs that mapped to a T-cell receptor pathway (P=0.0014). A risk index representing combined effects of 6 SNPs from the serotonergic pathway was associated with greater odds of localized TMD (odds ratio 2.7, P=1.3 E-09), and the result was reproduced in a replication case-control cohort study of 639 people (odds ratio 1.6, P=0.014). A risk index representing combined effects of 8 SNPs from the T-cell receptor pathway was associated with greater odds of TMD with widespread pain (P=1.9 E-08), although the result was not significant in the replication cohort. These findings illustrate potential for clinical classification of chronic pain based on distinct molecular profiles and genetic background.

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.

The longitudinal course of temporomandibular joint (TMJ) disc displacement (DD) and degenerative joint disease (DJD) has never been conclusively described with magnetic resonance imaging and computed tomography, respectively. This 8-y observational study’s objective was to assess the longitudinal stability of DD and DJD among 401 subjects. The Validation Project provided baseline measures; follow-up was performed in the TMJ Impact Project. With magnetic resonance imaging, 2 radiologists rendered a consensus diagnosis of normal/indeterminate, DD with reduction, or DD without reduction. Computed tomography consensus diagnoses included normal/indeterminate, grade 1 DJD, or grade 2 DJD. Radiologist reliability was assessed by kappa; a Hui-Walter model was used to estimate, after accounting for diagnostic disagreement, the frequency of diagnostic progression and reversal. Permutation tests were used to test the statistical influence of concurrent baseline diagnoses on diagnostic changes at follow-up. Of 789 baseline joint-specific soft tissue diagnoses of DD, 598 (76%) joints showed no change; 109 (14%) demonstrated progression; and 82 (10%) had reversal. Of 794 joints with baseline joint-specific hard tissue diagnoses of DJD, progression was observed in 122 (15%) joints, no change in 564 (71%), and reversal in 108 (14%). Radiologist reliability (kappa) was 0.73 (95% CI, 0.64 to 0.83) for DD and 0.76 (95% CI, 0.68 to 0.83) for DJD. After accounting for the influence of diagnostic disagreement, progression of hard tissue diagnoses in the right TMJ occurred in 15.2% of subjects (95% CI, 10.5% to 20.8%) and reversal in 8.3% (95% CI, 4.9% to 12.3%); results were similar for soft tissue diagnoses and the left TMJ. Concurrent baseline soft tissue diagnoses were associated with hard tissue diagnostic changes at follow-up ( P < 0.0001). Baseline hard tissue diagnoses showed no statistical association with soft tissue changes at follow-up ( P = 0.11). Longitudinally, 76% of baseline TMJ soft tissue diagnoses and 71% of the baseline hard tissue diagnoses remained stable. Diagnostic reversal and progression were confirmed for both soft and hard tissues.

The demographic factors of sex, age, and race/ethnicity are well recognized as relevant to pain sensitivity and clinical pain expression. Of these, sex differences have been the most frequently studied, and most of the literature describes greater pain sensitivity for women. The other 2 factors have been less frequently evaluated, and current literature is not definitive. Taking advantage of the large Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study cohort, we evaluated the association of sex, age, and self-reported race with 34 measures of pressure, mechanical, and thermal pain sensitivity encompassing threshold and suprathreshold perception. Women were significantly more pain-sensitive than men for 29 of 34 measures. Age effects were small, and only significant for 7 of 34 measures, however, the age range was limited (18–44 years of age). Race/ethnicity differences varied across groups and pain assessment type. Non-Hispanic white individuals were less pain-sensitive than African-American (for 21 of 34 measures), Hispanic (19 of 34), and Asian (6 of 34) individuals. No pain threshold measure showed significant racial differences, whereas several suprathreshold pain measures did. This suggests that racial differences are not related to tissue characteristics or inherent nociceptor sensitivity. Rather, the differences observed for suprathreshold pain ratings or tolerance are more likely related to differences in central nociceptive processing, including modulation imposed by cognitive, psychological, and/or affective factors. Perspective The influence of sex, age, and race/ethnicity on various aspects of pain sensitivity, encompassing threshold and suprathreshold measures and multiple stimulus modalities, allows for a more complete evaluation of the relevance of these demographic factors to acute pain perception.

Aims: To determine if retrospective self-report of oral parafunctional behaviors potentially relevant to pain conditions is valid, by comparing oral parafunctional behaviors via a self-report instrument (Oral Behaviors Checklist [OBC]) with in-field reports of oral parafunction. Methods: Individuals with a range of oral parafunctional behaviors, as identified by the OBC, were recruited, and 22 completed the field study. Using the Ecological Momentary Assessment paradigm, each subject was randomly prompted about eight times per day, for a target of 7 days, via portable handheld computer to report current behaviors among 11 queried items. Before and after the field study, a paper version of the OBC was administered. Separately, 74 individuals participated in a test-retest study of the paper OBC. Analyses included regression, correlation, intraclass correlation coefficient (ICC) and area under the receiving operating curve (AUC). Results: Pre- and postfield study administration of the OBC exhibited substantial reliability (ICC = 0.65), indicating no reactivity during the intervening in-field data collection. Reliability across in-field days was low, indicating high variability in which behavior occurred on which day. Nonobservable behaviors were reported more frequently than observable behaviors. Self-report via OBC was linear with in-field data collection methods (R2 values ranged from 0.1 to 0.7; most values were within 0.3 to 0.4). The predictive value of the self-report total score was AUC (0.88) relative to the in-field study score. Separate test-retest reliability of the OBC was almost perfect (ICC = 0.88). Conclusions: The OBC is a reliable and valid way to predict behaviors in the natural environment and will be useful for further pain research.

Cross-cultural differences in pain sensitivity have been identified in pain-free subjects as well as in chronic pain patients. The aim was to assess the impact of culture on psychophysical measures using mechanical and electrical stimuli in patients with temporomandibular disorder (TMD) pain and pain-free matched controls in three cultures. This case-control study compared 122 female cases of chronic TMD pain (39 Saudis, 41 Swedes and 42 Italians) with equal numbers of age- and gender-matched TMD-free controls. Pressure pain threshold (PPT) and tolerance (PPTo) were measured over one hand and two masticatory muscles. Electrical perception threshold and electrical pain threshold (EPT) and tolerance (EPTo) were recorded between the thumb and index fingers. Italian females reported significantly lower PPT in the masseter muscle than other cultures (P < 0.001) and in the temporalis muscle than Saudis (P = 0.003). Swedes reported significantly higher PPT in the thenar muscle than other cultures (P = 0.017). Italians reported significantly lower PPTo in all muscles than Swedes (P ≤ 0.006) and in the masseter muscle than Saudis (P < 0.001). Italians reported significantly lower EPTo than other cultures (P = 0.01). Temporomandibular disorder cases, compared to TMD-free controls, reported lower PPT and PPTo in all the three muscles (P < 0.001). This study found cultural differences between groups in the PPT, PPTo and EPTo. Overall, Italian females reported the highest sensitivity to both mechanical and electrical stimulation, while Swedes reported the lowest sensitivity. Mechanical pain thresholds differed more across cultures than did electrical pain thresholds. Cultural factors may influence response to type of pain test.

The perception of pain varies considerably across individuals and is affected by psychological traits. This study aimed to investigate the combined effects of somatosensory amplification and trait anxiety on orthodontic pain. Five-hundred and five adults completed the State Trait Anxiety Inventory (STAI) and the Somatosensory Amplification Scale (SSAS). Individuals with combined STAI and SSAS scores below the 20th percentile (LASA group: five men and 12 women; mean age ± SD = 22.4 ± 1.3 yr) or above the 80th percentile (HASA group: 13 men and seven women; mean age ± SD = 23.7 ± 1.0 yr) were selected and filled in the Oral Behaviors Checklist (OBC). Orthodontic separators were placed for 5 d in order to induce experimental pain. Visual analog scales (VAS) were administered to collect ratings for occlusal discomfort, pain, and perceived stress. Pressure pain thresholds (PPT) were measured. A mixed regression model was used to evaluate pain and discomfort ratings over the 5-d duration of the study. At baseline, the LASA group had statistically significantly higher PPT values for the masseter muscle than did the HASA group. During the experimental procedure, the HASA group had statistically significantly higher discomfort and pain. A significant difference in pain ratings during the 5 d of the study was found for subjects in the HASA group. Higher OBC values were statistically significantly positively associated with pain. Somatosensory amplification and trait anxiety substantially affect experimentally induced orthodontic pain.

The classification of most chronic pain disorders gives emphasis to anatomical location of the pain to distinguish one disorder from the other (eg, back pain vs temporomandibular disorder [TMD]) or to define subtypes (eg, TMD myalgia vs arthralgia). However, anatomical criteria overlook etiology, potentially hampering treatment decisions. This study identified clusters of individuals using a comprehensive array of biopsychosocial measures. Data were collected from a case-control study of 1031 chronic TMD cases and 3247 TMD-free controls. Three subgroups were identified using supervised cluster analysis (referred to as the adaptive, pain-sensitive, and global symptoms clusters). Compared with the adaptive cluster, participants in the pain-sensitive cluster showed heightened sensitivity to experimental pain, and participants in the global symptoms cluster showed both greater pain sensitivity and greater psychological distress. Cluster membership was strongly associated with chronic TMD: 91.5% of TMD cases belonged to the pain-sensitive and global symptoms clusters, whereas 41.2% of controls belonged to the adaptive cluster. Temporomandibular disorder cases in the pain-sensitive and global symptoms clusters also showed greater pain intensity, jaw functional limitation, and more comorbid pain conditions. Similar results were obtained when the same methodology was applied to a smaller case-control study consisting of 199 chronic TMD cases and 201 TMD-free controls. During a median 3-year follow-up period of TMD-free individuals, participants in the global symptoms cluster had greater risk of developing first-onset TMD (hazard ratio = 2.8) compared with participants in the other 2 clusters. Cross-cohort predictive modeling was used to demonstrate the reliability of the clusters.

Analysis of previous data suggested the hypothesis that temporomandibular joint (TMJ) eminence shapes develop ideally to minimize joint loads. Hence, we tested this hypothesis in nine females and eight males in each of two groups, with and without TMJ disc displacement. Participants provided anatomical data used in a joint load minimization numerical model to predict, and jaw-tracking data used to measure, eminence shapes. Coordinate data (x,y) of shapes were fit to third-order polynomials for two sessions, sides, and methods (predicted, measured) for each participant. Inter-session data were reliable and averaged. Those with, compared with those without, disc displacement had higher measured shape range (5:1) and left-right asymmetry prevalence (4:1). In 29 symmetrical individuals, ANCOVA and Bonferroni tests compared vertical dimensions (y) at 11 postero-anterior points (x), 0.5 mm apart. Model-predicted and measured shapes were significantly different (P ≤ 0.01) near the eminence crest, but joint load minimization was consistent with eminence shape for x < 3.0 mm.

For musculoskeletal disorders like low back pain and fibromyalgia, evidence is growing for fear of movement to play an important role in the development of chronic pain. In temporomandibular disorder (TMD) patients, however, this construct has not received any attention yet. Therefore, in this paper, (1) a generally used instrument to measure fear of movement, the Dutch version of the Tampa Scale for Kinesiophobia (TSK), was adapted for its use in TMD patients (and translated for equivalence to English), (2) the psychometric properties of the Dutch version of the TSK-TMD were assessed, and (3) the association of various symptoms of TMD (i.e., pain, joint sounds, and limited jaw movements) with fear of movement was evaluated. In a sample of TMD patients (N = 301), confirmatory factor analysis indicated that a two-factor model based on 12 items provides the best fit of the TSK-TMD, with activity avoidance and somatic focus as its subscales. This two-factor solution of the Dutch TSK-TMD has generally good reliability and convergent validity. Multiple regression analysis showed that TMD functional problems (i.e., temporomandibular joint sounds or a stuck/locked feeling) were more strongly associated with fear of movement than with pain. This finding leads to new perspectives regarding the interplay between musculoskeletal complaints, cognition, and avoidance behavior. The results provide a basis for use of the 12-item version for routine assessment of fear of movement in TMD patients, and for future clinical studies, for example, to the role of fear of movement in TMD-treatment success.

In contrast to sleep-related oral parafunctional behaviors, little is known about waking oral parafunctional behaviors. The Oral Behaviors Checklist contains terms referring to a variety of non-observable behaviors that are reliable when prompted (e.g. 'clench') but validity data are absent. Our goal was to assess whether (i) each behavioral term is distinct electromyographically, and (ii) temporomandibular disorder (TMD) subjects differ from non-TMD subjects in their performance. Surface electromyographic (EMG) activity was used to measure bilateral masseter, temporalis, and suprahyoid muscles while subjects (27 patients with TMD; 27 healthy controls) performed ten oral behaviors without explanation. Electromyographic data were averaged between bilateral muscles and two trials. A multivariate construct (jaw muscle activity) was analyzed using Wilks lambda within multivariate analysis of variance (manova). Obvious behaviors (e.g. clench, read, tongue press) exhibited expected EMG patterns, and patients and controls produced identical profile plots of the EMG data. Of 10 tested behaviors, nine were found to be associated with significantly differing proportions of amplitudes across muscles and were thus unique. Behaviors with similar terms were associated with different EMG patterns. The present data support the specificity of behavioral terms and performances. Implications include causation related to TMD based on subtle behaviors that occur at a high frequency.

c s m c r t i t g s c p n w i e s n H o ase Review A61-year-old woman presented to her general dentist with a complaint of pain associated with the maxillary left first premolar. The paient described a sharp, lancinating pain that was trigered by stimulation of the tooth in question. She also eported 2 specific episodes in which she experienced evere, shooting electrical shock-like pain followed by a ot sensation in the same area. One of these episodes as triggered by a cool breeze on her face and the other ccurred while washing her face. Examination and radioraphic assessment revealed a periapical osseous lesion esulting in a diagnosis of acute apical periodontitis. onsurgical endodontics was completed with no undue ffects. Approximately 2 months after the endodontic treatent, the patient began to have a recurrence of the aroxysmal sharp, shooting pain with a marked increase n the frequency of these episodes. The pain was trigered by light touch of the left cheek. Each episode asted 1 to 2 seconds; however, she occasionally had 5 to 0 repetitive bursts. Clinical evaluation resulted in a dignosis of trigeminal neuralgia of the left maxillary diviion. Initial treatment included 100 mg carbamazepine id., which was gradually increased to a maximum dose f 600 mg bid. The patient derived modest benefit from he medication; unfortunately, cognitive changes necesitated a reduction in the dose. Gabapentin was introuced in a bedtime dosage regimen of 100 mg. This rovided a marked reduction in pain for approxiately 1 week. A gradual titration of gabapentin to 00 mg tid was efficacious for approximately 1 month. eurosurgical consultation and MRI of the brain reealed no intracranial pathology and confirmed a dignosis of trigeminal neuralgia. Surgical intervention s being considered.

Objectives: This research aims to assess the test-retest reliability, the face, content and known groups validity, and responsiveness to change, of OHIP-TMDs, a 22-item TMDs-specific version of the Oral Health Impact Profile (OHIP). Methods: Test-retest reliability - A group of patients with TMDs (n = 20) was administered OHIP-TMDs twice before initial consultation with a 2-week interval. Face and content validity - Content validity index assessments were undertaken with professionals and patients. Known groups validity - Participants (n = 76) with confirmed Axis 1 RDC/TMD diagnoses completed OHIP-TMDs prior to TMDs treatment. Their responses were compared, using inferential statistics, with those of age- and gender-matched controls. Responsiveness to change - Using the same 76 participants, a comparison was made of OHIP-TMDs with OHIP-49 (order of administration randomized) both at baseline and 3 months after starting treatment. Results: OHIP-TMDs showed good test-retest reliability ICC (2,1) 0.805 (95% CI: 0.565, 0.918); good face and content validity; significant differences (P < 0.001) between controls and participants demonstrating known groups validity. Its responsiveness to change was similar to OHIP-49. Conclusions: OHIP-TMDs is an appropriate biopsychosocial, patient-centred, outcome measure for assessing QOL in patients with TMDs. It is less than half the length of OHIP-49 and contains proportionately more items relevant to TMDs.

The overall purpose of this study was to determine whether adolescents with chronic temporomandibular disorder (TMD) pain are more sensitive to all types of somatic and emotional stimuli compared with a matched healthy control group. Sixty adolescents, 8 boys and 52 girls ranging from 12 to 18 years, participated in the study. Thirty of the subjects exhibited TMD, reporting pain of at least 3 months duration. The age- and gender-matched control group consisted of 30 dental recall patients who reported TMD pain less than once a week. All participants completed a 40-item questionnaire comprising 10 items each of pleasant and aversive qualities crossed with somatic and emotional forms of stimuli. The items, a selection of a broad range of familiar stimuli by a panel of experts, were rated based on intensity of experience (0–10, numerical rating scale). Well-fitting items that formed a valid construct within each of the four domains were selected using Rasch analysis. The results showed that adolescents with TMD pain reported significantly greater sensitivity ðp < 0:05Þ to aversive somatic and pleasant somatic stimuli than the controls. The differences between groups for the aversive emotional and pleasant emotional stimuli were non-significant. These findings suggest that chronic TMD pain states in adolescents are accompanied by amplification of bodily, but not purely emotional stimuli and that cognitive systems are implicated, not only an alteration of the nociceptive systems. 2004 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.

Aims The aim was to study achieved competences in temporomandibular disorders (TMD)/orofacial pain (OP) at two universities by comparing student's knowledge and understanding, satisfaction with their education and confidence in their clinical competences of TMD/OP. Methods The study was conducted in collaboration between Malmo University, Sweden—which uses problem-based learning—and the University of Naples Federico II, Italy—which uses traditional educational methods. Final-semester dental students responded to a self-report questionnaire regarding their knowledge and understanding, interpretation of cases histories, clinical experience, satisfaction and confidence in clinical examination, management and treatment evaluation. Results No significant difference was found between the students regarding knowledge and understanding. Eighty-seven per cent of the Malmo students and 96% of the Naples students met the criterion on achieved competence. Malmo students had a higher per cent of correct diagnoses than Naples students in the interpretation of case histories. Overall, Malmo students reported most clinical experience and higher confidence than Naple students. Conclusions The main findings were that students from Malmo and Naples were, similar in knowledge and understanding of TMD/OP and in satisfaction with their clinical competences. However, Malmo students perceived more confidence in clinical management of patients with TMD/OP. This may reflect that, besides the theoretical part of the programme, a sufficient level of clinical exposure to patients with TMD/OP is essential to gain competences in TMD/OP.

Central sensitization elicits pain hypersensitivity and is thought to be causally implicated in painful temporomandibular disorder (TMD). This causal inference is based on cross-sectional evidence that people with TMD have greater sensitivity than controls to noxious stimuli. We tested this inference in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort study of 3258 adults with no lifetime history of TMD when enrolled (visit 1). During 5 years of follow-up, 1 group labeled "persistent TMD cases" (n=72) developed first-onset TMD by visit 2 that persisted ⩾ 6 months until visit 3. Another group labeled "transient TMD cases" (n=75) developed first-onset TMD at visit 2, which resolved by visit 3. Randomly sampled "controls" (n=126) remained TMD-free throughout all 3 visits. At each visit, pressure pain thresholds (PPTs) were measured by algometry at 10 cranial and bodily sites. In persistent TMD case patients, mean PPTs reduced 43 kPa (P

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. Perspective This 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.

Incidence of temporomandibular disorder (TMD) was predicted with multivariable models that used putative risk factors collected from initially TMD-free individuals in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. The 202 baseline risk factors included sociodemographic and clinical characteristics, measures of general health status, experimental pain sensitivity, autonomic function, and psychological distress. Study participants (n = 2,737) were then followed prospectively for a median of 2.8 years to ascertain cases of first-onset TMD. Lasso regression and random forest models were used to predict incidence of first-onset TMD using all of the aforementioned measures. Variable importance scores identified the most important risk factors, and their relationship with TMD incidence was illustrated graphically using partial dependence plots. Two of the most important risk factors for elevated TMD incidence were greater numbers of comorbid pain conditions and greater extent of nonspecific orofacial symptoms. Other important baseline risk factors were preexisting bodily pain, heightened somatic awareness, and greater extent of pain in response to examiners' palpation of the head, neck, and body. Several demographic variables persisted as risk factors even after adjusting for other OPPERA variables, suggesting that environmental variables not measured in OPPERA may also contribute to first-onset TMD. Perspective Multivariable methods were used to identify the most important predictors of first-onset TMD in the OPPERA study. Important variables included comorbid pain conditions, preexisting pain, and somatic awareness. Demographic characteristics, which probably reflect environmental variables not measured in OPPERA, also appear to play an important role in the etiology of TMD.

Due to disparate findings across the published studies, the stress-hyperactivity hypothesis has never been fully accepted as a causal mechanism for chronic muscle pain. Two recent comprehensive reviews of the psychophysiological studies of chronic pain came to opposite conclusions about the viability of the hypothesis, which stemmed from differing importance placed on the experimental methodology: the adequacy of stress manipulation. The present study tested the hypotheses that the adequacy of stress manipulation is influenced by stress stimuli type, degree of personal relevance, and selection of criterion for verification of stress experience, and that these factors have a measurable impact on the related physiological responses in a manner that is consistent with a theory of stress applicable to clinical stress disorders. The three factors investigated were: task (imagery, reaction time), relevance (high, low), and manipulation criterion (autonomic, self-report). The tasks were presented to 16 chronic pain patients while muscle, electrodermal, and self-report responses were recorded. Reaction-time tasks and high-relevance conditions led to high muscle and electrodermal responses. Only the high-relevance imagery, however, produced high self-reported distress. Consistent with other research, the present overall data demonstrated differing physiological profiles for different stimuli types. More importantly, these data suggest that the manipulation type and the manipulation criterion influence outcomes of experimental tests of stress on physiological systems, which may directly lead to contrasting conclusions about causal relations between stress and chronic pain conditions.

The ascending Method of Limits, used for the determination of pressure pain thresholds (PPT), is not a psychophysically robust method. The present study sought to determine if the examiner's expectancy, based on whether the measurement site was clinically 'painful' or 'non-painful', would bias the obtained PPT values. Twenty-eight patients with facial or temporal area pain served as subjects, and in each subject, a pain site and a control site were identified and marked. According to a randomization schedule, the pain and control sites were correctly marked in half of the subjects and were mis-labeled in the other half, thereby controlling the examiner's knowledge of a site and thus the examiner's expectancy of what the PPT should be. Two examiners, shown to be reliable with each other in both pre-clinical and post-clinical reliability studies, were blind to the true purpose of the study and to the marking procedures. Each examiner made one PPT measurement at each marked site in a counterbalanced measurement order. Manipulating the examiner's prior knowledge of the measurement site's characteristics significantly lowered the obtained PPT values for control sites but did not significantly alter the PPT at the clinically painful sites. Nevertheless, the pain sites still had significantly lower PPTs than did control sites. We conclude that: (i) PPTs at pain sites are robust to a major source of measurement bias associated with the ascending Method of Limits; (ii) measurement order and knowledge of measurement site characteristics can influence obtained PPT; and (iii) the common protocol in which the examiner monitors the amount of pressure during PPT measurement in order to control the force application rate may serve as a mechanism that can bias the obtained values.

Factors influencing natural history and clinical course of pain in temporomandibular disorders (TMD) are largely unknown. Physical, psychological and behavioral data from a population-based epidemiologic study of TMD were examined in 234 cases of persons reporting TMD pain. The cases were assigned to one of five pain pattern groups based on changes in average TMD pain from baseline to 5-year follow-up: (i) remitted (49% of the sample), (ii) high-improvement (14%), (iii) low-improvement (9%), (iv) same (13%), and (v) worse (16%). For each pain change group, an ANOVA-derived pattern analysis was performed to assess whether the pattern of change in each of seven physical and three psychological variables was congruent or dissimilar to the pattern of change in average pain intensity. For none of the physical or psychological variables was the change over time completely congruent with the changes in pain. Changes in ambient average TMD pain were most closely related to those clinical variables whose assessment is influenced by pain or other self-reported symptoms (e.g., number of muscle sites painful to examiner palpation), while the amount of pain change was less closely related to changes in clinical variables, such as joint sounds, where assessment is not dependent on subjective report. The three psychological variables, anxiety, depression, and somatization, displayed similar change patterns, but these patterns were distinctly different from those of the physical variables in that the remitted pain group was at the population mean at baseline for these psychological variables and remained there; significant improvement in psychological status was observed only in the pain group showing high improvement. The other three pain change groups exhibited elevated psychological distress scores at both baseline and 5 years. These results indicate that although the relationships among the course of pain, of physical variables, and of psychological variables are complicated, the 5-year outcome in pain is largely independent of readily discernible changes in clinical signs.

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. Perspective 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.

The course of preclinical pain symptoms sheds light on the etiology and prognosis of chronic pain. We aimed to quantify rates of developing initial and recurrent symptoms of painful temporomandibular disorder (TMD) and to evaluate associations with health behaviors. In the OPPERA prospective cohort study, 2,719 individuals aged 18 to 44years with lifetime absence of TMD when enrolled completed 25,103 quarterly (3-monthly) questionnaires during a median 2.3-year follow-up period. Questionnaires documented TMD symptom episodes, headache, other body pain, health care attendance, and analgesic use, and. Kaplan-Meier methods for clustered data estimated symptom-free survival time. Multivariable models assessed demographic variation in TMD symptom rates and evaluated associations with health care and analgesic use. One-third of the study subjects developed TMD symptoms and for a quarter of symptomatic episodes, pain intensity was severe. Initial TMD symptoms developed at an annual rate of 18.8 episodes per 100 persons. The annual rate more than doubled for first-recurrence and doubled again for second or subsequent recurrence such that, 1year after first recurrence, 71% of study subjects experienced a second recurrence. The overall rate increased with age and was greater in African Americans and lower in Asians relative to those of white race/ethnicity. The probability of TMD symptoms was strongly associated with concurrent episodes of headache and body pain and with past episodes of TMD symptoms. Episodes of TMD symptoms, headache, and body pain were associated with increases of ∼10% in probability of analgesic use and health care attendance. Yet, even when TMD, headache, and body pain occurred concurrently, 27% of study subjects neither attended health care nor used analgesics.

Although cross-sectional studies of temporomandibular disorder (TMD) often report elevated prevalence in young women, they do not address the risk of its development. Here we evaluate sociodemographic predictors of TMD incidence in a community-based prospective cohort study of U.S. adults. Symptoms and pain-related disability in TMD cases are also described. People aged 18 to 44 years with no history of TMD were enrolled at 4 study sites when they completed questionnaires about sociodemographic characteristics. During the median 2.8-year follow-up period, 2,737 participants completed quarterly screening questionnaires. Those reporting symptoms were examined clinically and 260 had first-onset TMD. Additional questionnaires asked about severity and impact of their symptoms. Univariate and multivariable Cox regression models quantified associations between sociodemographic characteristics and TMD incidence. First-onset TMD developed in 3.9% of participants per annum, typically producing mild to moderate levels of pain and disability in cases. TMD incidence was positively associated with age, whereas females had only slightly greater incidence than males. Compared to whites, Asians had lower TMD incidence whereas African Americans had greater incidence, although the latter was attenuated somewhat after adjusting for satisfaction with socioeconomic circumstances. Perspective In this study of 18- to 44-year-olds, TMD developed at a higher rate than reported previously for similar age groups. TMD incidence was positively associated with age but weakly associated with gender, thereby differing from demographic patterns of prevalence found in some cross-sectional studies. Experiences related to aging merit investigation as etiologic influences on development of TMD.

Genetic risk factors are believed to combine with environmental exposures and contribute to the risk of developing temporomandibular disorder (TMD). In this prospective cohort study, 2,737 people without TMD were assessed for common genetic variation in 358 genes known to contribute to nociceptive pathways, inflammation, and affective distress. During a median follow-up period of 2.8 years, 260 people developed first-onset TMD. Hazard ratios were computed as measures of association between 2,924 single-nucleotide polymorphisms and TMD incidence. After correction for multiple testing, no single single-nucleotide polymorphism was significantly associated with risk of onset TMD. However, several single-nucleotide polymorphisms exceeded Bonferroni correction for multiple comparison or false discovery rate thresholds (.05, .1, or .2) for association with intermediate phenotypes shown to be predictive of TMD onset. Nonspecific orofacial symptoms were associated with voltage-gated sodium channel, type I, alpha subunit ( SCN1A , rs6432860, P = 2.77 × 10 −5 ) and angiotensin I–converting enzyme 2 ( ACE2 , rs1514280, P = 4.86 × 10 −5 ); global psychological symptoms with prostaglandin-endoperoxide synthase 1 ( PTGS1 , rs3842803, P = 2.79 × 10 −6 ); stress and negative affectivity with amyloid-β (A4) precursor protein ( APP , rs466448, P = 4.29 × 10 −5 ); and heat pain temporal summation with multiple PDZ domain protein ( MPDZ , rs10809907, P = 3.05 × 10 −5 ). The use of intermediate phenotypes for complex pain diseases revealed new genetic pathways influencing risk of TMD. Perspective This article reports the findings of a large candidate gene association study of first-onset TMD and related intermediate phenotypes in the OPPERA Study. Although no genetic markers predicted TMD onset, several genetic risk factors for clinical, psychological, and sensory phenotypes associated with TMD onset were observed.

Aims: We assessed and compared the diagnostic accuracy of two sets of diagnostic criteria for headache secondary to temporomandibular disorders (TMD). Methods: In 373 headache subjects with TMD, a TMD headache reference standard was defined as: self-reported temple headache, consensus diagnosis of painful TMD and replication of the temple headache using TMD-based provocation tests. Revised diagnostic criteria for Headache attributed to TMD were selected using the RPART (recursive partitioning and regression trees) procedure, and refined in half of the data set. Using the remaining half of the data, the diagnostic accuracy of the revised criteria was compared to that of the International Headache Society’s International Classification of Headache Diseases (ICHD)-II criteria A to C for Headache or facial pain attributed to temporomandibular joint (TMJ) disorder. Results: Relative to the TMD headache reference standard, ICHD-II criteria showed sensitivity of 84% and specificity of 33%. The revised criteria for Headache attributed to TMD had sensitivity of 89% with improved specificity of 87% ( p Conclusion: Having significantly better specificity than the ICHD-II criteria A to C, the revised criteria are recommended to diagnose headache secondary to TMD.

Central nervous system organization of masticatory muscles determines the magnitude of joint and muscle forces. Validated computer-assisted models of neuromuscular organization during biting were used to determine organization in individuals with and without temporomandibular disorders (TMD). Ninety-one individuals (47 women, 44 men) were assigned to one of four diagnostic groups based on the presence (+) or absence (-) of pain (P) and bilateral temporomandibular joint disc displacement (DD). Electromyography and bite-forces were measured during right and left incisor and molar biting. Two three-dimensional models employing neuromuscular objectives of minimization of joint loads (MJL) or muscle effort (MME) simulated biting tasks. Evaluations of diagnostic group and gender effects on choice of best-fit model were by analysis of variance (ANOVA) and Tukey-Kramer post hoc tests, evaluations of right-left symmetry were by Chi-square and Fisher’s exact statistics, and evaluations of model accuracy were by within-subject linear regressions. MME was the best-fit during left molar biting in +DD individuals and incisor biting in men (all p < 0.03). Incisor biting symmetry in muscle organization was significantly higher (p < 0.03) in healthy individuals compared with those with TMD. Within-subject regressions showed that best-fit model errors were similar among groups: 8 to 15% (0.68 ≤ R2 ≤ 0.74). These computer-assisted models predicted muscle organization during static biting in humans with and without TMDs.

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.