One-third of the UK population is composed of problem-oriented dental attenders, seeking dental care only when they have acute dental pain or problems. Patients seek urgent dental care from a range of health care professionals, including general medical practitioners. This study aimed to identify trends in dental attendance at Welsh medical practices over a 44-y period, specifically in relation to dental policy change and factors associated with repeat attendance. A retrospective observational study was completed via the nationwide Secure Anonymised Information Linkage (SAIL) Databank of visits to general medical practice in Wales. Read codes associated with dental diagnoses were extracted for patients attending their general medical practitioner between 1974 and 2017. Data were analyzed with descriptive statistics and univariate and multivariable logistic regression. Over the 44-y period, there were 439,361 dental Read codes, accounting for 288,147 patient attendances. The overall attendance rate was 2.60 attendances per 1,000 patient-years (95% CI, 2.59 to 2.61). The attendance rate was negligible through 1987 but increased sharply to 5.0 per 1,000 patient-years in 2006 (95% CI, 4.94 to 5.09) before almost halving to 2.6 per 1,000 in 2017 (95% CI, 2.53 to 2.63) to a pattern that coincided with changes to National Health Service policies. Overall 26,312 patients were repeat attenders and were associated with living in an area classified as urban and deprived (odds ratio [OR], 1.22; 95% CI, 1.19 to 1.25; P < 0.0001) or rural (OR, 0.84; 95% CI, 0.83 to 0.85; P < 0.0001). Repeat attendance was associated with greater odds of having received an antibiotic prescription (OR, 2.53; 95% CI, 2.50 to 2.56; P < 0.0001) but lower odds of having been referred to another service (OR, 0.75; 95% CI, 0.70 to 0.81; P < 0.0001). Welsh patients' reliance on medical care for dental problems was influenced by social deprivation and health policy. This indicates that future interventions to discourage dental attendance at medical practitioners should be targeted at those in the most deprived urban areas or rural areas. In addition, health policy may influence attendance rates positively and negatively and should be considered in the future when decisions related to policy change are made.

This study evaluates contributions of jaw injury and experimental pain sensitivity to risk of developing painful temporomandibular disorder (TMD). Data were from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) nested case-control study of incident painful TMD. Injury and subsequent onset of painful TMD were monitored prospectively for ≤5 y in a community-based sample of 409 US adults who did not have TMD when enrolled. At baseline, thermal-pressure and pinprick pain sensitivity, as potential effect modifiers, were measured using quantitative sensory testing. During follow-up, jaw injury from any of 9 types of potentially traumatic events was determined using quarterly (3-monthly) health update questionnaires. Study examiners classified incident painful TMD, yielding 233 incident cases and 176 matched controls. Logistic regression models, estimated incidence odds ratios (IORs), and 95% confidence limits (CLs) were used for the association between injury and subsequent onset of painful TMD. During follow-up, 38.2% of incident cases and 13.1% of controls reported 1 or more injuries that were 4 times as likely to be intrinsic (i.e., sustained mouth opening or yawning) as extrinsic (e.g., dental visits, whiplash). Injuries due to extrinsic events (IOR = 7.6; 95% CL, 1.6–36.2), sustained opening (IOR = 5.4; 95% CL, 2.4–12.2), and yawning (IOR = 3.4; 95% CL, 1.6–7.3) were associated with increased TMD incidence. Both a single injury (IOR = 6.0; 95% CL, 2.9–12.4) and multiple injuries (IOR = 9.4; 95% CL, 3.4,25.6) predicted greater incidence of painful TMD than events perceived as noninjurious (IOR = 1.9; 95% CL, 1.1–3.4). Injury-associated risk of painful TMD was elevated in people with high sensitivity to heat pain (IOR = 7.4; 95% CL, 3.1–18.0) compared to people with low sensitivity to heat pain (IOR = 3.9; 95% CL, 1.7–8.4). Jaw injury was strongly associated with elevated painful TMD risk, and the risk was amplified in subjects who had enhanced sensitivity to heat pain at enrollment. Commonly occurring but seemingly innocuous events, such as yawning injury, should not be overlooked when judging prognostic importance of jaw injury.

Measures of sympathetic and parasympathetic tone (or “autonomic factors,” such as blood pressure, heart rate, and heart rate variability) are known risk factors for several painful conditions. Here we investigate cross-sectional associations of autonomic factors with somatic symptoms, severity of pain, and sleep quality in subjects with chronic TMD (n=1062). They were community-based volunteers aged 18-44 years recruited from four U.S. study sites in the OPPERA study (Orofacial Pain, Prospective Evaluation and Risk Assessment). Somatic symptoms were measured with the Pennebaker Inventory of Limbic Languidness (PILL), average facial pain intensity in the last 30 days was measured with Gracely Pain Intensity and Unpleasantness Box Scale, and sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Measures of arterial blood pressure, heart rate (HR), heart rate variability, and indirect measures of baroreflex sensitivity were assessed at rest conditions and after orthostatic challenge using a BioCom 3000 electrocardiogram recorder. After controlling for age and gender, resting HR and SDNN (standard deviation of normal-to-normal [N-N] intervals) were positively associated with somatic symptoms, sleep problems, average pain intensity and unpleasantness. Resting total power (TP), very low, low, and high-frequency (VLF, LF, HF) bands were negatively correlated with somatic symptoms and sleep problems, but not with average pain intensity. SDNN, TP, VLF, LF, and HF measured after orthostatic challenge were strongly positively associated with somatic symptoms, sleep problems and average pain intensity and pain unpleasantness. These findings suggest that subjects with prevailing sympathetic tone as indicated by increased resting HR, decreased heart rate variability, and reduced HF band are more likely to express more somatic symptoms, higher pain intensity or unpleasantness, and poor sleep quality. Further studies are warranted whether an individual autonomic profile could be a prognostic factor for TMD progression and treatment outcomes.

Objective: To describe the reported oral health behaviours and perceptions of Indigenous Australians living in Darwin, Northern Territory and to compare those with estimates for Darwin and Australia derived from the National Survey of Adult Oral Health (NSAOH). Participants: A total of 181 Indigenous Australians aged 22 years and over living in Darwin, participating in screening for a wider randomised clinical trial, were included. Method: Information on socio-demographic characteristics, oral health status including oral health behaviours and perceptions was collected using a questionnaire. Differences between the Darwin study (DS) participants and Australians in NSAOH were made based on non-overlapping 95% confidence intervals. Results: Almost 72% of DS participants had last seen a dentist over a year earlier, compared to 47% and 39% of NSAOH Darwin and Australian participants, respectively. A higher proportion of DS participants usually visited a dentist because of a problem than NSAOH Darwin and NSAOH Australian participants. A higher proportion of DS participants had avoided or delayed a dental visit because of cost than NSAOH participants. Over three times as many DS participants rated their oral health as fair/poor compared to NSAOH participants. A higher proportion of DS participants had perceived gum disease and one or more symptoms of gum disease than NSAOH participants. A higher proportion of DS participants experienced toothache, felt uncomfortable about appearance of their mouth and avoided eating because of oral problems than NSAOH participants. Conclusions: A higher proportion of Indigenous Australians living in Darwin presented with non-optimal oral health behaviours and perceptions compared with both the Darwin and Australian general populations.

In addition to pain in the orofacial region, people with temporomandibular disorders (TMJD) frequently report chronic pain conditions in other parts of the body. They may also experience palpation tenderness elsewhere in the body. Clinically detecting individuals with these generalized pain features is critical for risk assessment and for treatment selection. We hypothesized that both localized TMJD pain and widespread palpation tenderness would be associated with greater likelihood of having multiple chronic pain conditions. In a case-control study, 311 females aged 18-60 years were examined for TMJD pain (i.e., arthralgia and/or myalgia based on Research Diagnostic Criteria for TMJD), and were assessed for tenderness in response to 3 pounds of digital palpation pressure applied at 18 pre-defined bodily sites. Widespread palpation tenderness (WPT) was defined as tenderness in contra-lateral (i.e., diagonal) body quadrants or in bilateral body sites. Three groups were classified as: 1) TMJD with WPT (n=78); 2) TMJD without WPT (n=66); and 3) Controls (i.e., individuals with neither TMJD nor WPT, n=167). Lifetime history of seven chronic pain conditions outside of the orofacial region was assessed by self-report. Standardized psychological scales were computed from additional self-complete questionnaires. In bivariate analysis, odds of having ≥2 chronic pain conditions was elevated 7-fold (OR 6.9, 95%CI = 2.9, 16.4) for TMJD without WPT relative to controls, and more than 30-fold (OR=32.6, 95%CI=13.7, 77.6) for TMJD with WPT relative to controls. In a multivariate generalized logistic regression model that adjusted for age, psychological and pain profiles, corresponding adjusted odds ratios were 3.3 (1.2, 9.2) and 7.0 (2.3, 21.8). These findings suggest that widespread palpation tenderness and TMJD pain both contribute to odds of having multiple chronic pain conditions elsewhere in the body, and the effects are not explained by psychological profiles or clinical pain. Supported by NIH DE016558, NS045685, PO1 NS045685-061A.

Traditionally, studies examining persistent post-motor vehicle collision (MVC) pain have focused on the neck region (Whiplash-Associated Disorders), however several recent studies have demonstrated that persistent post-MVC pain is not limited to the neck region. We assessed which regions of body pain are most associated with pain interference and other health outcomes 6 weeks after MVC using data from a prospective, multisite, longitudinal study of patients (n = 427) enrolled in the emergency department after MVC. Among patients reporting persistent post-MVC pain in one or more body regions 6 weeks after MVC (n = 321), we examined the strength of association (assessed via unstandardized beta regression coefficient) between pain severity (0-10 numeric rating scale) in each body region (Regional Pain Scale) and MVC-related pain interference (Brief Pain Inventory subscales) and other health outcomes: post-traumatic stress disorder (PTSD) symptoms (Impact of Events Scale-Revised), depressive symptoms (Center for Epidemiological Studies Depression Scale), and mental and physical health (Short Form 12 Health Survey MCS, PCS). For each outcome, pain regions were then ranked according to strength of association, and mean rankings across pain interference subscales were calculated. Pain in the neck region had the highest mean ranking across pain interference subscales 6 weeks after MVC, followed by pain in the abdomen, upper back, head, and lower back regions. Pain in the neck region was also most strongly associated with depressive symptoms, physical health, and mental health. Pain in the abdominal region was the next most strongly associated with these three outcomes, and was the pain region most strongly associated with comorbid PTSD symptoms. These findings broadly support an emphasis on the neck region when examining post-MVC pain outcomes, while highlighting the important influence of pain in a number of body regions on pain interference and emotional and physical health outcomes. Funded by NIH 1R01AR056328.

More than 4 million people present to US Emergency Departments (ED) annually for evaluation following motor vehicle collision (MVC). More than 90% of these patients do not have serious physical injury and are discharged to home after evaluation. Pain and postconcussive syndrome (PCS, most often defined as ≥ 3 new somatic/cognitive symptoms after trauma exposure) are common sequelae in such patients. However, these outcomes have rarely been studied together. We evaluated the association between PCS and pain severity in the immediate aftermath of MVC. Patients (n = 473) enrolled in a multi-site prospective observational study completed an ED research interview evaluating pain severity (0-10 numeric rating scale for twenty body regions), post concussion symptoms (Rivermead Post Concussion Symptoms Questionnaire (RPQ)), collision history, and presence or absence of head trauma during the collision. PCS presence was defined as ≥ 3 symptoms positive on the RPQ. Pain symptom differences were assessed using Mann-Whitney U-tests. Adjusted differences were assessed using multivariate logistic analyses. Forty three percent (205/473) of enrolled patients met criteria for PCS. Compared to patients without PCS, patients with PCS had higher mean overall pain score [6.3(2.2) vs 5.4(2.3), p<0.001], higher mean neck pain score [5.0(2.9) vs 3.4(3.0), p<0.001], and more body regions with pain [7.4(4.3) vs 4.5(2.9), p<0.001]. The associations between pain symptoms and PCS persisted after adjustment for collision type and the presence of head trauma. This suggests that the observed shared vulnerability to pain and PCS after MVC may not be attributable solely to factors related to the collision, and may instead be due to individual differences present prior to the collision. Further research examining pain and PCS outcomes after MVC is needed. Funded by NIH 1R01AR056328.

Catechol‐O‐methyltransferase (COMT) is a ubiquitously expressed enzyme that maintains basic biologic functions by inactivating catechol substrates. In humans, polymorphic variance at the COMT locus has been associated with modulation of pain sensitivity and risk for developing psychiatric disorders. A functional haplotype associated with increased pain sensitivity was shown to result in decreased COMT activity by altering mRNA secondary structure‐dependent protein translation. However, the exact mechanisms whereby COMT modulates pain sensitivity and behavior remain unclear and can be further studied in animal models. We have assessed Comt1 gene expression levels in multiple brain regions in inbred strains of mice and have discovered that Comt1 is differentially expressed among the strains, and this differential expression is cis‐regulated. A B2 short interspersed nuclear element (SINE) was inserted in the 3′‐untranslated region (3′‐UTR) of Comt1 in 14 strains generating a common haplotype that correlates with gene expression. Experiments using mammalian expression vectors of full‐length cDNA clones with and without the SINE element show that strains with the SINE haplotype (+SINE) have greater Comt1 enzymatic activity. +SINE mice also exhibit behavioral differences in anxiety assays and decreased pain sensitivity. These results suggest that a haplotype, defined by a 3′‐UTR B2 SINE element, regulates Comt1 expression and some mouse behaviors.

Temporomandibular disorder (TMD) is a painful musculoskeletal disorder involving the temporomandibular joint and muscles of the head and neck. Recent work by our group and others suggests that TMD results from enhanced states of pain amplification and psychological distress, and there is reason to expect both are driven by increased production of proinflammatory cytokines. This study aimed to determine the relationship between cytokines, pain sensitivity, and TMD. In a case-control study, we made comprehensive measurements of pain sensitivity and collected blood samples from 196 TMD cases and 198 healthy controls, all females aged 18-60 years recruited by advertisement and referral from pain clinics. Blood samples were assessed for 22 cytokines using a multiplex platform. Of these 22 cytokines, 3 were elevated in TMD cases relative to controls (monocyte chemoattractant protein-1; MCP-1, thrombopoietin; TPO, and vascular endothelial growth factor; VEGF). Among cases, 3 cytokines were associated with mechanical pressure (MCP-1, interleukin-8; IL-8, and macrophage inflammatory protein-1α; MIP1α), 1 with application of a single thermal stimulus (TPO), and 3 with windup to repeated thermal stimuli (TPO, IL-8, and interleukin-1 receptor antagonist; IL-1RA). Additionally, IL-8 was associated with number of bodily palpation sites such that TMD cases with widespread tenderness had the highest levels of IL-8. These represent distinct cytokine protein expression signatures associated with TMD case status and intermediate phenotypes, and suggest that 1) MCP-1 and TPO contribute to TMD via enhanced experimental pain sensitivity, 2) VEGF contributes to TMD via a mechanism not explored here, and 3) IL-8 defines a specific subgroup of TMD cases that present with concurrent widespread tenderness. Finally, these results demonstrate the utility of cytokines as diagnostic biomarkers and potential therapeutic targets for patients with TMD. (Supported by NINDS U01-DE017018 & P01 NSO45685 to W.M.; NIDCR R01 DE16558 to L.D.; NCRR K12/KL2 & OBSSR R24 to A.N.) Temporomandibular disorder (TMD) is a painful musculoskeletal disorder involving the temporomandibular joint and muscles of the head and neck. Recent work by our group and others suggests that TMD results from enhanced states of pain amplification and psychological distress, and there is reason to expect both are driven by increased production of proinflammatory cytokines. This study aimed to determine the relationship between cytokines, pain sensitivity, and TMD. In a case-control study, we made comprehensive measurements of pain sensitivity and collected blood samples from 196 TMD cases and 198 healthy controls, all females aged 18-60 years recruited by advertisement and referral from pain clinics. Blood samples were assessed for 22 cytokines using a multiplex platform. Of these 22 cytokines, 3 were elevated in TMD cases relative to controls (monocyte chemoattractant protein-1; MCP-1, thrombopoietin; TPO, and vascular endothelial growth factor; VEGF). Among cases, 3 cytokines were associated with mechanical pressure (MCP-1, interleukin-8; IL-8, and macrophage inflammatory protein-1α; MIP1α), 1 with application of a single thermal stimulus (TPO), and 3 with windup to repeated thermal stimuli (TPO, IL-8, and interleukin-1 receptor antagonist; IL-1RA). Additionally, IL-8 was associated with number of bodily palpation sites such that TMD cases with widespread tenderness had the highest levels of IL-8. These represent distinct cytokine protein expression signatures associated with TMD case status and intermediate phenotypes, and suggest that 1) MCP-1 and TPO contribute to TMD via enhanced experimental pain sensitivity, 2) VEGF contributes to TMD via a mechanism not explored here, and 3) IL-8 defines a specific subgroup of TMD cases that present with concurrent widespread tenderness. Finally, these results demonstrate the utility of cytokines as diagnostic biomarkers and potential therapeutic targets for patients with TMD. (Supported by NINDS U01-DE017018 & P01 NSO45685 to W.M.; NIDCR R01 DE16558 to L.D.; NCRR K12/KL2 & OBSSR R24 to A.N.)

In a small prospective study designed to identify key biological and psychological risk factors that predict the development of painful temporomandibular disorders (TMJD), we identified several psychological factors that predicted the risk of onset of TMJD. Constructs associated with many complex persistent pain conditions including somatization, depression, anxiety, and perceived stress were identified. We have also previously identified genetic loci associated with psychological domains that are associated with an increased risk for chronic persistent pain conditions.1 We now report preliminary results from a larger population-based cohort, the Orofacial Pain: Prospective Evaluation and Risk Assessment Study (OPPERA; www.oppera.org). Here we address the hypothesis that psychological factors representing putative causal influences for chronic pain onset and persistence are influenced by candidate genetic variants. Data from 3200 initially pain-free subjects enrolled into OPPERA from four clinical sites were used for this analysis. Enrollees completed a battery of questionnaires that assessed psychological phenotypes predictive of chronic pain. These tests included the State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), Pennebaker Inventory for Limbic Languidness (PILL), Profile of Mood States (POMS), and the Brief Symptom Inventory (BSI). DNA from subjects who donated blood was genotyped using a Parallele MIP technology microarray chip comprised of 3295 single-nucleotide polymorphisms (SNPs), representing 350 genes known to influence psychological and nociceptive pathways (see www.cogenics.com). This panel was specifically designed to assay polymorphisms most likely to regulate gene expression and function, as well as comprehensively “tag” the entire gene locus. Linear regression was used to associate quantitative test scores with genetic markers, using PLINK software. Ongoing analyses are identifying an array of genetic variants relevant to psychological distress that contribute to the complex pathology underlying the onset and maintenance of persistent pain conditions. (1. Slade, J Dent Res, 2007.)

Temporomandibular disorder (TMD) is a painful musculoskeletal disorder involving the temporomandibular joint and muscles of the head and neck. Comorbid pain conditions associated with TMD include fibromyalgia, chronic fatigue, headache, vulvar pain, and irritable bowel syndrome. The pathophysiology of TMD and related conditions is largely unknown and conventional therapeutics possess limited efficacy. Identification of biological mediators that contribute to the development of TMD will lead to more accurate subdiagnoses and rational treatment strategies. Recent studies conducted by our group suggest that TMD is mediated by enhancements in pain processing which may occur, at least in part, through the stimulation of proinflammatory cytokines. Elevated levels of cytokines such as tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 are associated with increased pain behavior in animals and painful inflammatory and musculoskeletal disorders in humans. The purpose of the present work is to characterize the relationship between proinflammatory cytokine profiles, pain sensitivity, and psychological status in TMD cases relative to controls. Our research team has acquired a clinical dataset containing assessments of pain sensitivity and psychological distress for TMD cases and healthy controls. Blood samples were also collected for measuring cytokine RNA abundance using real time PCR and protein levels using multiplex and ELISA technology. While statistical analyses are currently ongoing, we propose that study participants diagnosed with TMD will differ regarding the severity of their disorder, related intermediate phenotypes, and cytokine profiles. Specifically, we hypothesize that increased proinflammatory cytokine production will be associated with heightened pain sensitivity and psychological distress in TMD cases. The outcome of these studies will contribute to the identification of unique molecular markers for the diagnosis of clinical pain conditions as well as provide novel targets for developing effective individualized therapeutics for TMD and related conditions. Supported by NINDS-P01-NS045685 to WM, NIDCR-R01-DE016558 to LD, NICHHD-K12-HD052191 to AN.

PURPOSE:This study was designed to assess the impact of "pain and swelling" associated with third molars on patients' quality of life before surgery.PATIENTS AND METHODS:The data for these analyses were obtained from a larger ongoing study designed to examine the surgical and medical management of problems associated with third molars. Data from 480 patients with 4 third molars scheduled for removal were used in the analysis. Questionnaires administered presurgery assessed patients' medical and dental history, their reasons for seeking third molar removal, and sociodemographic characteristics. Adverse impacts on oral health-related quality of life were measured using the 14-item Oral Health Impact Profile (OHIP) questionnaire. The primary outcome variable was the percentage of people reporting 1 or more of the 12 non-pain-specific OHIP items "fairly often" or "very often" during the 3 months before enrollment.RESULTS:One third (178 of 480) of patients said they were seeking third molar surgery because of current or previous symptoms of pain/swelling, and 17% reported 1 or more of the 12 non-pain-specific OHIP items. In the multivariate logistic regression model, the odds of one or more impacts was greater for people who presented because of symptoms (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.7 to 4.8), who were aged 25 years or more (OR, 1.9; 95% CI, 1.1-3.3), and who had a self-reported history of tooth loss due to pathology or trauma (OR, 2.9; 95% CI, 1.9 to 5.5).CONCLUSIONS:Adverse impacts on quality of life occurred for 1 in 8 patients seeking third molar surgery, and the odds increased 3-fold for patients who had experienced pain/swelling compared with those who were asymptomatic.

AIHW cat. no. DEN 165. "Australian Research Centre for Population Oral Health, The University of Adelaide Australia"