OBJECTIVE: This study assessed the impact of migraine and fibromyalgia (FM) in TMD patients, focusing on pain, anxiety, depression, and quality of life (QoL). Additionally, we investigated how these variables relate to the total number of comorbidities to gain insights into their interactions.
METHODS: A retrospective data collection was conducted during January 2016 to December 2022, involving 409 adult TMD patients. TMD patients were categorised into four groups: those without comorbidity (TMD-only) and those with comorbid migraine and/or fibromyalgia (TMD + MG, TMD + FM and TMD + MG + FM). Quantitative variables were compared among them. Linear regression was used to analyse the associations between these variables.
RESULTS: Most of study population were women (79%) with a mean age of 44.43 years. TMD + MG patients reported longer pain duration, higher pain scores and greater pain interference compared with TMD-only patients. Similarly, TMD + FM patients had higher pain intensity than patients with TMD only. Both the TMD + MG and TMD + FM groups had higher levels of anxiety, depression, and health impairment compared with patients with TMD only. Patients with all three pain conditions (TMD + MG + FM) experienced the longest pain duration, highest pain intensity, psychological distress, and impaired QoL. The result showed positive associations between pain outcomes, psychological measures, pain\'s impact on QoL, and the number of comorbidities and a negative association between overall health states and the number of comorbidities.
CONCLUSIONS: These findings underscore the importance of considering the presence of comorbidities and addressing physical and psychological aspects in the management of TMD patients.

BACKGROUND: Injections of botulinum toxin type A (BoNT-A) have been proposed as an additional treatment modality for patients suffering chronic temporomandibular disorder (TMD)-related myofascial pain (MFP). BoNT-A impairs muscle function, along with its analgesic effect, and a minimal effective dose should be used. The objective of this randomized placebo-controlled crossover study was to evaluate the clinical benefit of a moderate dose (50 U) of BoNT-A.
METHODS: Sixty-six subjects were randomized into two groups, one which received BoNT-A first and a second which received a saline solution (SS) first. Follow-ups were performed 2, 11, and 16 weeks after the injections. Diagnostic criteria for temporomandibular disorders (DC/TMD) diagnostic algorithms were used to evaluate characteristic pain intensity (CPI) and pain-related disability based on the Graded Chronic Pain Scale (GCPS). Electromyographic and bite force were also evaluated.
RESULTS: The within-group analysis showed a significant improvement in pain intensity and pain-related disability after BoNT-A (p < 0.001, p = 0.005, p = 0.011) and SS (p = 0.003, p = 0.005, p = 0.046) injections up to week 16. The between-group analysis of pain-related variables revealed no differences between groups at any time. Nonetheless, BoNT-A, but not SS, caused a significant decline in muscle performance. The number needed to treat (NNT) regarding a clinically significant pain reduction (≥30%) was 6.3, 57.0, and 19.0 at 2, 11, and 16-week follow-ups favoring BoNT-A.
CONCLUSIONS: Injections of 50 U of BoNT-A might improve MFP symptoms, but the specific effect of the drug on pain compared to the placebo is not obvious.

BACKGROUND: Depression and anxiety have been suggested to be associated with temporomandibular disorders (TMD) in observational studies. However, the causal association and the direction in the relationship between depression/anxiety and TMD remain unknown.
OBJECTIVE: This study investigated the potential causal relationship between depression/anxiety and TMD with two-sample bi-directional Mendelian randomization (MR).
METHODS: Summary statistics of depression (N = 500 199), anxiety disorder (N = 17 310) and TMD (N = 195 930) were sourced from large-scale genome-wide association studies (GWAS). The primary Mendelian randomization (MR) estimation employed the inverse-variance weighted meta-analysis (IVW). Additional MR sensitivity methods and multivariate MR (MVMR) were applied to address pleiotropy.
RESULTS: IVW results indicated a causal effect of genetically predicted depression on TMD (OR = 1.887, 95% CI = 1.504-2.367, p < .001), which was supported by other sensitivity MR approaches. MVMR results suggested that the negative effect of depression on TMD persisted after conditioning on other potential confounders. The association of anxiety disorder with TMD was not supported by our findings. In the reverse direction, we did not find compelling evidence suggesting the causal effect of TMD on depression and anxiety disorder.
CONCLUSIONS: The present study suggests a potential causal association between genetic liability for depression and the risk of TMD. Our MR findings align with prior epidemiological research, underscoring the significance of early detection and prevention of depression in the treatment of TMD.

Background and Objectives: Temporomandibular disorders or dysfunction (TMDs) encompass a range of complex conditions that impact the temporomandibular joint (TMJ), chewing muscles, teeth, and/or their supporting tissues. Stress is one of the most associated factors studied as a TMD predictor. The aim is to figure out the influence of stress on TMJ status and salivary cortisol in university students during and before exams. Materials and Methods: The study was non-experimental, employing a longitudinal, analytical, observational cohort design. The study population consisted of students enrolled in the physiotherapy degree program at the Alfonso X El Sabio University (Madrid, Spain). Data were collected during two distinct academic periods: the first period was characterized by low academic stress and no exams, and the second period coincided with the high academic stress of final course exams. The collected results included sociodemographic data, assessment of TMJ status (Fonseca Index), evaluation of muscle evaluation (masseter, upper trapezius, and sternocleidomastoid) using a MOXY Monitor (muscle oxygenation) and Neurotrac® (surface EMG, sEMG), assessment of perceived stress (PSS-14), and measurement of salivary cortisol (enzyme immunoassay with Elisa). The statistical analysis was conducted with a confidence level of 95% (p ≤ 0.05) and asymptotic or bilateral significance. Results: 70 students were analyzed during two different measurement periods. According to the Fonseca Index, initially, 37.14% of the analyzed students showed mild TMDs, 17.14% moderate TMDs, and 45.72% showed no TMDs. In general terms, stress increased with age and is related to female sex, maximum mouth opening decreased with age, oxygen saturation decreased with age and academic stress, and myoglobin concentration was related to age. Furthermore, muscle contraction decreased during higher academic stress and increased with age. For women, age was a risk factor for suffering from TMDs, and stress worsened the transition from having TMDs to having no TMDs in both sexes. Conclusions: Academic stress influences TMJ status and muscle outcomes such as oxygen saturation, myoglobin concentration, and muscle contraction, although more research is needed.

UNASSIGNED: To investigate the relationship between T102C (rs6313) polymorphism in the 5-hydroxytryptamine receptor-2A (5HTR2A) gene and temporomandibular disorder (TMD) and anxiety.
UNASSIGNED: This observational case-control study included 80 patients and 70 healthy controls. TMD was diagnosed using the criteria for TMD (DC/TMD). Anxiety was assessed with the Beck anxiety scale. A genotyping study of HTRR2A T102C (rs6313) gene polymorphism was performed from genomic DNA isolated from blood.
UNASSIGNED: The TMD group had higher anxiety scores than the control group (p < .05). The TMD group was similar to the control group regarding genotype and allele frequencies. However, the polymorphic CC genotype was more common in those with high anxiety (p < .05).
UNASSIGNED: There was no clear evidence of an association between TMD and the T102C polymorphism in HTR2A and TMD. However, anxiety is closely related to the T102C polymorphism in HTR2A.

BACKGROUND: Activation of β2 adrenergic receptors reduces cutaneous mechanical pain thresholds in rats. While β2 adrenergic receptor activation may contribute to mechanisms that underlie temporomandibular joint pain, its effect on masticatory muscle pain sensitivity is uncertain.
OBJECTIVE: The current study sought to determine the extent to which β adrenergic receptors are expressed by masticatory muscle afferent fibres, and to assess the effect of local activation of these receptors on the mechanical sensitivity of masticatory muscle afferent fibres in rats.
METHODS: Trigeminal ganglion neurons that innervate the rat (n = 12) masseter muscle and lower lip were identified by tissue injection of fluorescent dyes and were then stained with antibodies against β1 or β2 adrenergic receptors. Extracellular recordings from 60 trigeminal ganglion neurons that innervate the masticatory muscle were undertaken in a second group of anaesthetised rats of both sexes (n = 37) to assess afferent mechanical activation thresholds. Thresholds were assessed before and after injection of the β adrenergic receptor agonists into masticatory muscle.
RESULTS: β1 and β2 adrenergic receptor expression was greater in labial skin than in masticatory muscle ganglion neurons (p < .05, one-way ANOVA, Holm-Sidak test). There was a higher expression of β2 adrenergic receptors in masticatory muscle ganglion neurons in males than in females. The mixed β agonist isoproterenol increased afferent mechanical activation threshold in male but not female rats (p < .05, Mann-Whitney test). In male rats, salbutamol, a β2 selective agonist, also increased afferent mechanical activation threshold but hydralazine, a vasodilator, did not (p < .05, Mann-Whitney test).
CONCLUSIONS: Activation of β2 adrenergic receptors decreases the mechanical sensitivity of masticatory muscle afferent fibres in a sex-related manner.

BACKGROUND: Painful temporomandibular disorder (TMD) is the common cause of chronic oro-facial pain, which may interfere with sleep. Previous studies have documented an association between sleep and TMD.
OBJECTIVE: This study aimed to further explore the association of night-time sleep and daytime napping with painful TMD.
METHODS: A total of 419 patients (aged 31.88 ± 11.54 years with women forming 85.4%) from a TMD/Orofacial Pain center were enrolled. Patients\' sleep conditions were evaluated with the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and information on night-time sleep duration, napping duration and napping frequency was interviewed. TMD was diagnosed according to the Diagnostic Criteria for TMD protocol and stratified into myalgia (muscle pain), arthralgia (joint pain) and combined (muscle and joint pain) subgroups. The severity of TMD was measured with the Fonseca Anamnestic Index (FAI) questionnaire. Restricted cubic spline (RCS) regression models were established to explore relationships between sleep and painful TMD subgroups.
RESULTS: Patients with poor sleep quality (PSQI≥6) had higher FAI scores (median 60, p < .001) and higher proportions of painful TMDs. The myalgia subgroup had higher PSQI scores (median 8, p < .001) than the arthralgia subgroup. The RCS models indicated a non-linear relationship between night-time sleep duration and myalgia (p < .001), which was not observed in arthralgia. However, there were no significant findings concerning napping and painful TMD subgroups.
CONCLUSIONS: This study found that the association between sleep and TMD is mainly related to painful TMD conditions, which are associated with night-time sleep duration.

Temporomandibular disorders (TMDs) refer to a group of conditions that affect the temporomandibular joint, causing pain and dysfunction in the jaw joint and related muscles. The diagnosis of TMDs typically involves clinical assessment through operator-based physical examination, a self-reported questionnaire and imaging studies. To objectivize the measurement of TMD, this study aims at investigating the feasibility of using machine-learning algorithms fed with data gathered from low-cost and portable instruments to identify the presence of TMD in adult subjects. Through this aim, the experimental protocol involved fifty participants, equally distributed between TMD and healthy subjects, acting as a control group. The diagnosis of TMD was performed by a skilled operator through the typical clinical scale. Participants underwent a baropodometric analysis by using a pressure matrix and the evaluation of the cervical mobility through inertial sensors. Nine machine-learning algorithms belonging to support vector machine, k-nearest neighbours and decision tree algorithms were compared. The k-nearest neighbours algorithm based on cosine distance was found to be the best performing, achieving performances of 0.94, 0.94 and 0.08 for the accuracy, F1-score and G-index, respectively. These findings open the possibility of using such methodology to support the diagnosis of TMDs in clinical environments.

UNASSIGNED: This study aimed to investigate the relationship between temporomandibular joint (TMJ) effusion and TMJ pain, as well as jaw function limitation in patients via two-dimensional (2D) and three-dimensional (3D) magnetic resonance imaging (MRI) evaluation.
UNASSIGNED: 121 patients diagnosed with temporomandibular disorder (TMD) were included. TMJ effusion was assessed qualitatively using MRI and quantified with 3D Slicer software, then graded accordingly. In addition, a visual analogue scale (VAS) was employed for pain reporting and an 8-item Jaw Functional Limitations Scale (JFLS-8) was utilized to evaluate jaw function limitation. Statistical analyses were performed appropriately for group comparisons and association determination. A probability of p<0.05 was considered statistically significant.
UNASSIGNED: 2D qualitative and 3D quantitative strategies were in high agreement for TMJ effusion grades (κ = 0.766). No significant associations were found between joint effusion and TMJ pain, nor with disc displacement and JLFS-8 scores. Moreover, the binary logistic regression analysis showed significant association between sex and the presence of TMJ effusion, exhibiting an Odds Ratio of 5.168 for females (p = 0.008).
UNASSIGNED: 2D qualitative evaluation was as effective as 3D quantitative assessment for TMJ effusion diagnosis. No significant associations were found between TMJ effusion and TMJ pain, disc displacement or jaw function limitation. However, it was suggested that female patients suffering from TMD may be at a risk for TMJ effusion. Further prospective research is needed for validation.

OBJECTIVE: The objective of this study was to investigate the relationship of the depression level with temporomandibular disorders (TMDs) in young conscripts as a population with chronic stresses.
METHODS: A total number of 144 male conscripts with chronic stress and different levels of depression were assigned to four groups according to the Beck\'s Depression Inventory (BDI). The control group consisted of age-matched male conscripts without chronic stress. The diagnosis of TMD was made according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Data were analyzed using Mann-Whitney and chi-square tests.
RESULTS: The participants with severe depression were significantly more susceptible to have TMD (p = .001) followed by the moderate depression, borderline clinical depression, mild mood disturbance, and control groups. The TMD diagnoses were more prevalent within depression groups compared with the control population (p = .01).
CONCLUSIONS: The level of depression is directly associated with the presence of TMD in young men with chronic stress.