Chronic Temporomandibular Disorder Pain Research Articles

Chronic temporomandibular disorder pain patients with a history of neuropathic pain treatment: a narrative research on their diagnosis and treatment history

The aims of this qualitative research were (1) to gain more insight in the diagnostic and treatment history of patients with chronic temporomandibular disorder (TMD) pain; (2) to get a deeper understanding of possible factors that are involved in the possible delay in setting a TMD-pain diagnosis and receiving appropriate treatment; and (3) to get a deeper understanding of the perspectives and experiences of chronic TMD-pain patients on the possible improvement of various aspects of their diagnostic and treatment journey.MethodsIn this narrative research, semi-structured interviews took place with patients who experienced chronic orofacial pain (OFP) for at least three years before getting diagnosed with, and treated for, TMD pain by an OFP specialist in an interprofessional setting.ResultsIn total, ten patients were interviewed in-depth. Patients experienced their chronic OFP in different ways, but all reported a significant impact of their pain on their quality of life. All patients visited numerous health care professionals before their TMD diagnosis was set. Among others, they underwent anti-neuropathic pain medication therapies and invasive surgeries, which did not significantly reduce their chronic OFP. The interprofessional TMD-pain treatment reduced the suffering of the chronic OFP substantially, also 6 months after the start of therapy, and improved the quality of life for all patients. In most of them, the OFP intensity was also decreased.ConclusionChronic TMD-pain patients with a history of neuropathic pain treatment may experience a long journey until receiving the appropriate diagnosis and treatment. This stresses the need to improve the implementation of chronic TMD-pain guidelines.

Whole-genome methylation profiling reveals regions associated with painful temporomandibular disorders and active recovery processes.

Temporomandibular disorders (TMDs), collectively representing one of the most common chronic pain conditions, have a substantial genetic component, but genetic variation alone has not fully explained the heritability of TMD risk. Reasoning that the unexplained heritability may be because of DNA methylation, an epigenetic phenomenon, we measured genome-wide DNA methylation using the Illumina MethylationEPIC platform with blood samples from participants in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Associations with chronic TMD used methylation data from 496 chronic painful TMD cases and 452 TMD-free controls. Changes in methylation between enrollment and a 6-month follow-up visit were determined for a separate sample of 62 people with recent-onset painful TMD. More than 750,000 individual CpG sites were examined for association with chronic painful TMD. Six differentially methylated regions were significantly ( P < 5 × 10 -8 ) associated with chronic painful TMD, including loci near genes involved in the regulation of inflammatory and neuronal response. A majority of loci were similarly differentially methylated in acute TMD consistent with observed transience or persistence of symptoms at follow-up. Functional characterization of the identified regions found relationships between methylation at these loci and nearby genetic variation contributing to chronic painful TMD and with gene expression of proximal genes. These findings reveal epigenetic contributions to chronic painful TMD through methylation of the genes FMOD , PM20D1 , ZNF718 , ZFP57 , and RNF39 , following the development of acute painful TMD. Epigenetic regulation of these genes likely contributes to the trajectory of transcriptional events in affected tissues leading to resolution or chronicity of pain.

Awake and Sleep Oral Behaviours in Patients With Painful Temporomandibular Disorders

The aim of this research was to explore the oral behaviours exhibited by individuals with and without temporomandibular disorders (TMD) pain, and with various pain characteristics; and to determine which oral behaviour is correlated with painful TMD. 328 patients with TMD who visited Orofacial Pain Clinic were included in this retrospective cross-sectional study. The patients were categorised into 2 groups-painful TMD and non-painful TMD-based on pain status; their other pain characteristics were recorded. To evaluate oral behaviours, researchers utilised the Oral Behaviors Checklist (OBC) and categorised into 3 levels based on the Diagnostic criteria for TMD scoring manual. To investigate the associations amongst demographic information, oral behaviour levels, and TMD pain status and characteristics, logistic regression was employed, whilst t tests were used to analyse OBC scores. Logistic regression was also used to examine individual oral behaviours in relation to specific pain characteristics. Age and marital status were associated with TMD pain status. Significantly higher OBC scores were observed in chronic pain compared to acute pain group, but the scores were not significantly different for pain status and other pain characteristics. OBC score and level were associated solely with TMD pain chronicity. According to multivariate logistic regression, "clench or grind teeth when sleeping" was the strongest predictor of TMD pain and "place tongue forcibly against teeth" was the strongest predictor of chronic painful TMD. High oral behaviour level and OBC scores were associated with chronic painful TMD. Sleep bruxism was the strongest predictor of TMD pain. Age and marital status were correlated with TMD pain status. In the treatment of TMD, there can be potential benefits in addressing and managing oral parafunctional behaviours.

The Contribution of Insomnia and Obstructive Sleep Apnea on the Transition from Acute to Chronic Painful Temporomandibular Disorders and their Persistence: A Prospective 3-Month Cohort Study

ABSTRACT Background Insomnia, and Excessive Daytime Sleepiness (EDS), a surrogate marker of Obstructive Sleep Apnea (OSA), are common sleep-related conditions among painful temporomandibular disorders (TMD) patients. OSA was found to increase the risk of chronic painful TMD. Aims This prospective cohort study aims to determine the contribution of insomnia and EDS on acute to chronic painful TMD transition as well as its persistence when chronic pain is defined by: (i) duration (> 3 months), and (ii) dysfunction (Graded Chronic Pain Scale [GCPS II-IV]). Methods From 456 patients recruited between 2015 to 2021, through four locations in Canada, 378 completed the follow-up. A diagnosis was obtained using the Research Diagnostic Criteria or the Diagnostic Criteria for TMD. Insomnia was assessed with the Insomnia Severity Scale (ISS), and OSA was assessed using the Epworth Sleepiness Scale (ESS) which measures EDS, both at baseline. Patients completed the GCPS form at baseline and 3-month follow-up. Results Borderline associations were found between EDS and the transition or persistence of chronic painful TMD when chronic pain was defined by pain duration (RR adjusted_duration = 1.11, P = 0.07) and dysfunction (RRadjusted_dysfunction =1.40, P = 0.051). Furthermore, EDS was specifically associated with persistent painful TMD when chronic pain was defined by pain duration (RR = 1.13, 95%CI: 1.00-1.26, P = 0.04). Insomnia was not related to the study outcomes (RRadjusted_duration = 0.94, P = 0.27, RRadjusted_dysfunction =1.00, P = 0.99). Conclusion Results indicate that EDS contrary to insomnia predicted the persistence of chronic painful TMD at a 3-month follow-up.

Pressure release technique versus placebo applied to cervical and masticatory muscles in patients with chronic painful myofascial temporomandibular disorder: A randomised clinical trial.

The therapeutic approach to myofascial TMD should focus on pain relief and rehabilitation of function. This study investigated whether pressure release technique (PRT) is effective for reducing pain in people with chronic myofascial temporomandibular disorders (TMD). A single-blinded randomised parallel-group trial, with 3 months follow-up was conducted. A total of 72 patients were randomly allocated to receive PRT or sham PRT. Primary outcome was pain assessed with a visual analogue scale (VAS). Secondary outcomes included pressure pain thresholds (PPTs), range of opening of the mouth (ROM), Neck Disability Index (NDI), Pain Catastrophizing Scale (PCS), Tampa Scale for Kinesiophobia (TSK-11), State-Trait Anxiety Index (STAI) and State-Trait Depression Index (ST-DEP). All parameters were assessed at baseline, at the end of the treatment and at 3 months follow-up. Statistical analysis was performed by ANOVA. There were significant main effects of time, group and interaction between time and group (F ≥ 21.92; p < .001) on VAS pain. Post hoc tests showed a significant reduction in VAS pain scores in the PRT group (≥31.9%; p < .001). Effect sizes were moderate in the PRT group at all follow-up periods (≥1.25 Cohen's d). Also, there were significant effects of time in secondary outcomes (F ≥ 9.65; p < .001), and there were also interactions between time and group (F ≥ 3.82; p < .002) with better effects in the PRT group. The inclusion of PRT to conventional management with occlusal splints and self-care management appears to be effective to improve self-reported levels of pain in patients with chronic myofascial TMD pain. Retrospectively registered (ClinicalTrials.gov: NCT03619889).

Standardized Centella asiatica (ECa 233) extract decreased pain hypersensitivity development in a male mouse model of chronic inflammatory temporomandibular disorder

Chronic inflammatory temporomandibular disorder (TMD) pain has a high prevalence, and available nonspecific treatments have adverse side effects. ECa 233, a standardized Centella asiatica extract, is highly anti-inflammatory and safe. We investigated its therapeutic effects by injecting complete Freund’s adjuvant (CFA) into right temporomandibular joint of mice and administering either ibuprofen or ECa 233 (30, 100, and 300 mg/kg) for 28 days. Inflammatory and nociceptive markers, bone density, and pain hypersensitivity were examined. CFA decreased ipsilateral bone density, suggesting inflammation localization, which ipsilaterally caused immediate calcitonin gene-related peptide elevation in the trigeminal ganglia (TG) and trigeminal subnucleus caudalis (TNC), followed by late increase of NaV1.7 in TG and of p-CREB and activation of microglia in TNC. Contralaterally, only p-CREB and activated microglia in TNC showed delayed increase. Pain hypersensitivity, which developed early ipsilaterally, but late contralaterally, was reduced by ibuprofen and ECa 233 (30 or 100 mg/kg). However, ibuprofen and only 100-mg/kg ECa 233 effectively mitigated marker elevation. This suggests 30-mg/kg ECa 233 was antinociceptive, whereas 100-mg/kg ECa 233 was both anti-inflammatory and antinociceptive. ECa 233 may be alternatively and safely used for treating chronic inflammatory TMD pain, showing an inverted U-shaped dose–response relationship with maximal effect at 100 mg/kg.

Application of photobiomodulation for chronic pain-related TMD on pain points versus pre-established points: Randomized clinical trial.

Photobiomodulation therapy (PTB) is a therapeutic possibility for temporomandibular disorders (TMD), but its effectiveness and protocols for use remain controversial. This study is a RCT that compared the effectiveness of PTB on pain points of the masticatory muscles and TMJs, located through palpation versus application of pre-established points in women with painful TMD, diagnosis by DC/TMD (Diagnostic Criteria for Temporomandibular Disorders - Brazilian Portuguese version). Therefore, a total sample of 54 women, aged between 18 and 60years, was investigated. Volunteers were randomly randomized and PTB was applied in four different groups with a dose of 4J and 6J divided into pre-established application points (PE - G1) and pain points (PD - G2) - Groups 4PE, 4PD, 6PE and 6PD. Four laser applications were performed with a wavelength of 780nm, one session per week, totaling one month of therapy. The following assessments were performed: DC/TMD, Brief Pain Inventory (BPI), McGill Questionnaire - Short Version (SF-MPQ) and Pain Intensity, Visual Analogue Scale (VAS). Friedman's test was used for within-group comparisons, while the Mann-Whitney test was used for between-group comparisons (p<0.05). According to the results, laser application on pain points (G2) was more effective. McGill's results showed that regardless of dose, the pain point application group had better outcomes (p=0.004). Pain intensity evaluation (last days) also showed that application at the pain points was more effective regardless of dose (p=0.0002). Medians and interquartile deviations showed overall that PTB was more effective at pain points, with a trend towards better outcomes at the 6J dose. Therefore, it can be concluded that in women with chronic painful TMD, the application of PTB at pain points is more effective than the application at pre-established points. Therefore, individualized PTB protocols are proposed, based on examination palpation of the masticatory structures.

Altered brain responses to noxious dentoalveolar stimuli in high-impact temporomandibular disorder pain patients.

High-impact temporomandibular disorder (TMD) pain may involve brain mechanisms related to maladaptive central pain modulation. We investigated brain responses to stimulation of trigeminal sites not typically associated with TMD pain by applying noxious dentoalveolar pressure to high- and low-impact TMD pain cases and pain-free controls during functional magnetic resonance imaging (fMRI). Fifty female participants were recruited and assigned to one of three groups based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and Graded Chronic Pain Scale: controls (n = 17), low-impact (n = 17) and high-impact TMD (n = 16). Multimodal whole-brain MRI was acquired following the Human Connectome Project Lifespan protocol, including stimulus-evoked fMRI scans during which painful dentoalveolar pressure was applied to the buccal gingiva of participants. Group analyses were performed using non-parametric permutation tests for parcellated cortical and subcortical neuroimaging data. There were no significant between-group differences for brain activations/deactivations evoked by the noxious dentoalveolar pressure. For individual group mean activations/deactivations, a gradient in the number of parcels surviving thresholding was found according to the TMD pain grade, with the highest number seen in the high-impact group. Among the brain regions activated in chronic TMD pain groups were those previously implicated in sensory-discriminative and motivational-affective pain processing. These results suggest that dentoalveolar pressure pain evokes abnormal brain responses to sensory processing of noxious stimuli in high-impact TMD pain participants, which supports the presence of maladaptive brain plasticity in chronic TMD pain.

Education-Enhanced Conventional Care versus Conventional Care Alone for Temporomandibular Disorders: A Randomized Controlled Trial

The objective of this study was to determine the effect of enhancing conventional care for people with chronic painful temporomandibular disorders (TMD) with an individualised contemporary pain science education (PSE) intervention. In this randomized controlled trial, a consecutive sample of 148 participants (18–55 years of age) was randomized into 2 groups: PSE-enhanced conventional care or Conventional care alone. Conventional care involved a 6-week, 12-session manual therapy and exercise program. The PSE enhancement involved 2 sessions of modern PSE, undertaken in the first 2 treatment sessions. Primary outcomes were pain intensity, assessed with a numeric pain rating scale, and disability, assessed with the craniofacial pain and disability inventory, post-treatment. Linear mixed model analyses were used to investigate between-group differences over time. There was a statistically and clinically meaningful effect of PSE enhancement on disability (Mean Difference = 6.1, 95% CI: 3.3–8.8), but not on pain intensity, post-treatment. Secondary analyses suggested clinically meaningful benefit of PSE enhancement on pain and disability ratings at 10-week and 18-week follow-ups, raising the possibility that preceding conventional care with a PSE intervention may result in long-term benefits. PerspectiveThe addition of modern Pain Science Education (PSE) intervention improved disability for people with chronic TMD receiving manual therapy and exercise, but not pain. A mean difference in pain and disability favoring the PSE group at the 10- and 18-week follow-ups, respectively, suggests that PSE addition resulted in longer-lasting effects. Trial registration: NCT03926767. Registered on April 29, 2019. https://clinicaltrials.gov/ct2/show/NCT03926767

CATASTROPHIZING, CENTRAL SENSITIZATION AND CHRONIC PAIN-RELATED TMD: HOW IS THIS ASSOCIATION?

INTRODUCTION: most of the individuals who present catastrophizing and central sensitization also present chronic pain, as temporomandibular disorders (TMD). AIM: to analyze whether there is an association between the variables of pain intensity, central sensitization, and catastrophizing in women with chronic pain-related TMD. METHODS: an observational descriptive cross-sectional study was conducted, comprising a sample of 50 women diagnosed with chronic pain-related TMD according to the DC/TMD – Brazilian Portuguese version. The following questionnaires/protocols were applied: Pain Catastrophizing Scale (PCS), Central Sensitization Inventory (BP-CSI)), pain intensity (Visual Analogue Scale, VAS). For the analysis of the PCS and CSI scores, the 75th percentile was used to determine the cutoff points, and Multiple Linear Regression Tests (p &lt; 0.05) was applied. RESULTS: The sample showed overall higher cutoff values ​​for catastrophization (32.3), rumination (12.4), magnification (5.7), helplessness (13.9), and central sensitization (52.2). Statistical association was found between the time of pain-related TMD (in months), number of painful points, and total catastrophizing score (F = 0.72; p = 0.004). This association was not found to central sensitization. That is, higher pain-related TMD time and/or higher number of painful points, also higher the catastrophizing. CONCLUSION: women with chronic painful TMD tend to have high levels of catastrophizing and central sensitization. There is a positive and proportional association between the duration of pain and/or the number of pailful points and catastrophizing in women with chronic pain-related TMD.

Genetic polymorphisms of TNF-α, IL-6, and IL-10 in female elderly patients with chronic temporomandibular disorder pain.

To verify the association of the TNF-α, IL-6, and IL-10 polymorphisms with chronic temporomandibular disorder pain development in female elderly patients. Participants were evaluated according to Diagnostic Criteria for Temporomandibular Disorders. The genomic DNA was extracted from blood according to the Salting Out method followed by a quantification using the NanoDrop spectrophotometer. The -308G/A TNF-α polymorphism analysis was performed by the polymerase chain reaction-restriction fragmentlength polymorphism technique, the determination of -174G/C IL-6 polymorphism was performed by polymerase chain reaction, and the evaluation of the -1082A/G IL-10 polymorphism was carried out by polymerase chain reaction- allele-specificamplification. Data were analyzed using the BioEstat 5.3 software. The -308G/A TNF-α polymorphism showed a significant difference when genotypes of cases with chronic temporomandibular disorder pain and controls were compared (p=.025). There was a lack of association regarding the -174G/C IL-6 polymorphism (p=.286) however, a positive association between the -1082A/G IL-10 polymorphism with chronic temporomandibular disorder was observed (p=.020). The analyzed data of elderly subjects support the possible involvement of the GA genotype of the -308G/A TNF-α and the AA genotype of the -1082A/G IL-10 polymorphisms in the pathogenesis of chronic temporomandibular disorder pain.

Mindfulness and pain catastrophization: how are they associated in women with chronic painful temporomandibular disorder (TMD)?

ABSTRACT Objective Pain catastrophizing has dimensions of magnification, rumination, and helplessness, being an important evaluator of chronic pain. Studies with mindfulness intervention point to a possible modulation of chronic pain catastrophizing behavior. However, how these facets of mindfulness are associated with the catastrophizing subscales is uncertain. The scope of this study is to verify how the association of mindfulness facets and catastrophizing subdimensions occurs. Methods Women with chronic TMD answered the Pain Catastrophizing Scale (PCS) and Five Facets of Mindfulness Questionnaire (FFMQ). Results Magnification was inversely correlated with “not reacting,” “not judging,” and the total FFMQ score. Total PCS was also inversely correlated with “not reacting.” Conclusion It is necessary to consider such possible correlations between mindfulness facets and the catastrophizing subdimensions in mindfulness-based interventions for this population.

Influence of cognitive performance on the response to pain education guidelines in patients with chronic painful temporomandibular disorders

Influence of cognitive performance on the response to pain education guidelines in patients with chronic painful temporomandibular disorders

Acute and Chronic Temporomandibular Disorder Pain: A critical review of differentiating factors and predictors of acute to chronic pain transition.

The aims of this critical review were to: (i) assess the factors that differentiate acute from chronic temporomandibular disorders (TMD) pain; (ii) assess the risk factors associated with the transition from acute to chronic TMD pain; and (iii) summarize and appraise the studies. The databases used were MEDLINE, Embase, and Cochrane Database of Systematic Reviews. Eligible studies included articles comparing acute to chronic TMD pain, and cohort studies assessing the risk factors implicated in the transition from acute to chronic TMD pain. Seven articles were selected: one case-control study, three cross-sectional studies, and three cohort studies. These studies found that psychological factors were more common in chronic than acute TMD pain patients; however, these factors did not increase the transition risk in the multivariable model. Myofascial and baseline pain intensity were associated with the transition from acute to chronic TMD pain at a 6-month follow-up. Due to methodological weaknesses in the available literature, more research is required to establish the risk factors implicated in the transition from acute to chronic TMD pain. This review found some evidence that myofascial pain is associated with the transition risk from acute to chronic TMD pain at a 6-month follow-up and that pain intensity at baseline is associated with more intense TMD pain 6months later. There is insufficient evidence to draw conclusions about the role of demographics and psychological disorders as independent risk factors.

PAX7 gene polymorphism in muscular temporomandibular disorders as potentially related to muscle stem cells

BackgroundTemporomandibular disorders (TMD) are a group of painful and debilitating disorders, involving the masticatory muscles and/or the temporomandibular joint (TMJ). Chronic TMD pain can be associated with genetic changes in the key muscle development genes.ObjectiveTo evaluate the association between polymorphisms in the PAX7 (paired box 7) gene and masticatory myalgia in patients with temporomandibular disorders (TMD).Materials and methodsThis is a case-control study. Patients with TMD were divided into two groups: (a) presence of muscular TMD (n = 122) and (b) absence of muscular TMD (n = 49). Genomic DNA was obtained from saliva samples from all participants to allow for genotyping single nucleotide polymorphisms in PAX7 (rs766325 and rs6659735). Over-representation of alleles was tested using chi-square or Fisher’s exact tests. Values of p < 0.05 were considered to be statistically significant.ResultsIndividuals without muscular TMD were less likely to have the PAX7 rs6659735 GG genotype (p = 0.03). No associations were found for PAX7 rs766325.ConclusionsAlterations in PAX7 may influence muscular pathophysiology and individuals with TMD and the rs6659735 homozygous genotype (GG) are seemingly associated with muscular involvement of the disorder. No associations were found in the region rs766325.

Oral health–related quality of life of patients with acute and chronic temporomandibular disorder diagnostic subtypes

BackgroundStudies have indicated the negative effects of temporomandibular disorders (TMDs) on oral health–related quality of life (OHRQoL). The authors investigated the OHRQoL of patients with acute and chronic TMD subtypes. MethodsThe authors recruited a total of 830 patients. They derived TMD diagnoses using the Diagnostic Criteria for TMDs protocol involving symptom history, physical examination, and diagnostic imaging as indicated. The authors categorized patients into acute (≤ 3 months) or chronic (> 3 months) pain-related TMD (PT), nonpainful intra-articular TMD (IT), and combined TMD (CT) groups. They also gathered sociodemographic information and assessed OHRQoL with the Oral Health Impact Profile (OHIP)-TMDs. The authors evaluated data using 2-way analysis of variance and Bonferroni test and multiple regression analysis. ResultsPatients in the chronic PT and CT subgroups had significantly higher mean global OHIP scores than their acute counterparts. The authors observed significant acute-chronic differences in OHIP-TMDs domain scores in 5 and 2 domains for the PT and CT groups, respectively. Patients in the acute IT group had significantly higher functional limitation scores than those in the chronic IT group. The ranking of mean global scores, in descending order was CT, PT, and IT for acute TMDs and PT, CT, and IT for chronic TMDs, with significant differences observed among the 3 TMD subtypes (P < .001). ConclusionsBoth TMD chronicity and subtypes influenced OHRQoL. Painful TMDs (PT and CT) were associated with significantly poorer OHRQoL than nonpainful TMDs. TMD chronicity appeared to affect OHRQoL only for the painful TMD conditions. Future work on the impact of TMDs on OHRQoL should strive to stratify patients by TMD chronicity and subtypes. Practical ImplicationsTMD chronicity and subtypes influence the impact of TMDs on OHRQoL. Given that chronic painful TMDs impair quality of life, early biopsychosocial intervention of acute TMD pain is important for minimizing chronification and OHRQoL deterioration.

Neuroimmune interactions in painful TMD: Mechanisms and treatment implications.

The underlying mechanisms and treatment of painful temporomandibular disorders (TMDs) are important but understudied topics in craniofacial research. As a group of musculoskeletal diseases, the onset of painful TMD is proved to be a result of disturbance of multiple systems. Recently, emerging evidence has revealed the involvement of neuroimmune interactions in painful TMD. Inflammatory factors play an important role in peripheral sensitization of temporomandibular joint (TMJ), and neurogenic inflammation in turn enhances TMJs dysfunction in TMD. Furthermore, centralized neuroimmune communications contribute to neuron excitability amplification, leading to pain sensitization, and is also responsible for chronic TMD pain and other CNS symptoms. Therapeutics targeting neuroimmune interactions may shed light on new approaches for treating TMD. In this review, we will discuss the role of neuroimmune interactions in the onset of painful TMD from the peripheral and centralized perspectives, and how understanding this mechanism could provide new treatment options. Insights into the neuroimmune interactions within TMJs and painful TMD would broaden the knowledge of mechanisms and treatments of this multifactorial disease.

17β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats.

Pain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Western blot and immunofluorescence to investigate the role and underlying mechanisms of estrogen in dental experimental occlusal interference (EOI)-induced chronic masseter mechanical hyperalgesia in rats. We found that long-term 17β-estradiol (E2) replacement exacerbated EOI-induced masseter hyperalgesia in a dose-dependent manner in ovariectomized (OVX) rats. Whole-cell patch-clamp recordings demonstrated that E2 (100 nM) treatment enhanced the excitability of isolated trigeminal ganglion (TG) neurons in OVX and OVX EOI rats, and EOI increased the functional expression of transient receptor potential vanilloid-1 (TRPV1). In addition, E2 replacement upregulated the protein expression of TRPV1 in EOI-treated OVX rats. Importantly, intraganglionic administration of the TRPV1 antagonist AMG-9810 strongly attenuated the facilitatory effect of E2 on EOI-induced masseter mechanical sensitivity. These results demonstrate that E2 exacerbated EOI-induced chronic masseter mechanical hyperalgesia by increasing TG neuronal excitability and TRPV1 function. Our study helps to elucidate the E2 actions in chronic myogenic TMD pain and may provide new therapeutic targets for relieving estrogen-sensitive pain.

Transitioning to chronic temporomandibular disorder pain: A combination of patient vulnerabilities and iatrogenesis.

ABSTRACTBackgroundBased on a variety of studies conducted in recent years, some of the factors that might contribute to the negative treatment responses of some TMD patients have been elucidated.MethodsThis paper describes known vulnerability factors that make individuals susceptible to developing temporomandibular disorders (TMDs), as well as those that contribute to the perpetuation of such problems. In addition, the topic of iatrogenesis is discussed as a major contributor to the negative outcomes that can be seen in this field.ResultsAt the patient level, anatomical, psychosocial and genetic factors may contribute to individual vulnerability. The anatomy and pathophysiology of muscles, joints, disc and nerves may all be involved in predisposing to TMD symptoms, especially when the patients have pain elsewhere in the body. Among the psychosocial factors, some features may be elucidated by the DC/TMD axis II, while others (eg illness behaviour, Munchausen syndrome, lack of acceptance of non‐mechanical approaches) require careful evaluation by trained clinicians. Genetic predisposition to first onset TMDs and to chronification of symptoms has been identified for individuals with certain psychological traits, presence of comorbid conditions and certain abnormal clinical manifestations. Regarding iatrogenesis, sins of omission may influence the clinical picture, with the main ones being misdiagnosis and undertreatment. Joint repositioning strategies, occlusal modifications, abuse of oral appliances, use of diagnostic technologies, nocebo effect and complications with intracapsular treatments are the most frequent sins of commission that may contribute to chronification of TMDs. The patients who present with massive occlusal and jaw repositioning changes combined with persistent severe orofacial pain are not a rarity within TMD and orofacial pain canters; these patients are the most difficult ones to manage because of this horrific combination of negative factors.ConclusionsThe information presented in this paper will help clinicians to understand better why some individuals develop temporomandibular disorders, why some of them will progress to becoming chronic patients, and what the appropriate responses may be.

Long-term evaluation of temporomandibular disorders in association with cytokine and autoantibody status in young women

Temporomandibular disorders (TMD) is a chronic pain disease affecting 4–60% of general population. Its suggested etiology includes mechanical overloading to related structures, psychosocial factors, and genetic vulnerability. However, its pathogenesis is yet to be fully understood, especially in cases with a higher level of pain and more associated comorbidities. Recently chronic systemic inflammation and possible autoimmunity has been indicated in several pain conditions as the underlying mechanism of chronicity but this aspect has not been rigorously investigated in TMD. This article focuses on analyzing the levels of cytokines, chemokines, autoantibodies and nonspecific inflammatory markers and comparing their levels according to pain severity and duration in 66 female TMD patients in their 20 s and investigating their association with clinical indices of TMD and comorbidities. The high pain disability group showed decreased range of jaw function and more pain on palpation of capsule areas compared to the low pain disability group. Comorbidities such as anxiety and sleep disturbance were also significantly more prevalent. The level of IL-8 and IgG were significantly higher in the high pain disability group. IL-2, -8, -13, IFN- γ, RANTES, PGE2, and thrombopoietin levels showed a significant effect on indices reflecting jaw function, generalized pain intensity, and health related quality of life. Such results imply that longer pain duration and higher pain intensity is associated with higher levels of systemic inflammation suggesting the possible role of immunologic disturbance as an underlying factor of chronic TMD pain and warranting further investigation for its consideration in diagnosis and treatment.