Assessment of orofacial nociceptive behaviors of mice with the sheltering tube method: Oxaliplatin-induced mechanical and cold allodynia in orofacial regions.

Preclinical studies on pathological pain rely on the von Frey test to examine changes in mechanical thresholds and the acetone spray test to determine alterations in cold sensitivity in rodents. These tests are typically conducted on rodent hindpaws, where animals with pathological pain show reliable nocifensive responses to von Frey filaments and acetone drops applied to the hindpaws. Pathological pain in orofacial regions is also an important clinical problem and has been investigated with rodents. However, performing the von Frey and acetone spray tests in the orofacial region has been challenging, largely due to the high mobility of the head of testing animals. To solve this problem, we implemented a sheltering tube method to assess orofacial nociception in mice. In experiments, mice were sheltered in elevated tubes, where they were quickly accommodated because the tubes provided safe shelters for mice. Examiners could reliably apply mechanical stimuli with von Frey filament, cold stimuli with acetone spray, and light stimuli with a laser beam to the orofacial regions. We validated this method in Nav1.8-ChR2 mice treated with oxaliplatin that induced peripheral neuropathy. Using the von Frey test, orofacial response frequencies and nociceptive response scores were significantly increased in Nav1.8-ChR2 mice treated with oxaliplatin. In the acetone spray test, the duration of orofacial responses was significantly prolonged in oxaliplatin-treated mice. The response frequencies to laser light stimulation were significantly increased in Nav1.8-ChR2 mice treated with oxaliplatin. Our sheltering tube method allows us to reliably perform the von Frey, acetone spray, and optogenetic tests in orofacial regions to investigate orofacial pain.

RNA sequencing of the thalamus and rostral ventral medulla in rats with chronic orofacial pain.

Diagnosing and treating chronic orofacial pain is challenging due to its complex structure and limited understanding of its causes and mechanisms. In this study, we used RNA sequencing to identify differentially expressed genes (DEGs) in the rostral ventral medulla (RVM) and thalamus of rats with persistent orofacial pain, aiming to explore its development. DEGs were functionally analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results showed a significant association between immune response and pain in this model. Key DEG mRNA expression trends were further validated using real-time quantitative polymerase chain reaction (RT-PCR), confirming their crucial roles in chronic orofacial pain. After injecting complete Freund's adjuvant (CFA) into the bilateral temporomandibular joint cavity for 14 days, we observed 293 upregulated genes and 14 downregulated genes in the RVM, and 1086 upregulated genes and 37 downregulated genes in the thalamus. Furthermore, we identified 27 common DEGs with altered expression (upregulation) in both the thalamus and RVM, including Cd74, C3, Cxcl13, C1qb, Itgal, Fcgr2b, C5ar1, and Tlr2, which are pain-associated genes. Protein-protein interaction (PPI) analysis using Cytoscape revealed the involvement of Toll-like receptors, complement system, differentiation clusters, and antigen presentation-related proteins in the interaction between the thalamus and RVM. The results of this study show that the immune system seems to have a more significant influence on chronic orofacial pain. There may be direct or indirect influence between the thalamus and RVM, which may participate in the regulation of chronic orofacial pain.

Relationship between insomnia and pain in patients with chronic orofacial pain.

OBJECTIVE: Few studies have investigated specific associations between insomnia and orofacial pain (OFP). The aim of this cross-sectional study was to examine relationships of insomnia with pain, mental health, and physical health variables among treatment-seeking patients with chronic OFP. METHODS: OFP diagnosis, demographics, insomnia symptoms, pain intensity, interference, and duration, mental health measures, and number of medical comorbidities were extracted from the medical records of 450 patients receiving an initial appointment at a university-affiliated tertiary OFP clinic. T-tests compared differences between patients with and without insomnia symptomatology, and between patients with different insomnia subtypes (delayed onset/early wakening). RESULTS: Compared to patients without insomnia, those with elevated insomnia symptomatology (45.1%) reported higher pain intensity (60.70 ± 20.61 vs 44.15 ± 21.69; P < .001) and interference (43.81 ± 29.84 vs 18.40 ± 23.43; P < 0.001), depression/anxiety symptomatology (5.53 ± 3.32 vs 2.72 ± 2.66; P < 0.001), dissatisfaction with life (21.63 ± 6.95 vs 26.50 ± 6.21; P < .001), and number of medical comorbidities (6.72 ± 5.37 vs 4.37 ± 4.60; P < .001). Patients with Sleep Onset Latency insomnia (SOL-insomnia) (N = 76) reported higher pain intensity (t = 3.57; P < 0.001), and pain interference (t = 4.46; P < .001) compared to those without SOL-insomnia. Those with Early Morning Awakening insomnia (EMA-insomnia) (N = 71) did not significantly differ from those without EMA-insomnia on any of the variables. Differences remained significant after adjusting for age, sex, primary OFP diagnosis, and pain intensity. CONCLUSIONS: Insomnia is associated with pain outcomes and should be appropriately managed when treating patients with chronic OFP.

The roles of 5-HT in orofacial pain.

OBJECTIVES: Acute and chronic orofacial pain are very common and remain a vexing health problem that has a negative effect on the quality of life. Serotonin (5-HydroxyTryptamine, 5-HT) is a kind of monoamine neurotransmitter that is involved in many physiological and pathological processes. However, its role in orofacial pain remains inconclusive. Therefore, this review aims to summarize the recent advances in understanding the effect exerted by 5-HT on the modulation of orofacial pain. SUBJECTS AND METHODS: An extensive search was conducted on PubMed and Web of Science for pertinent studies focusing on the effects of 5-HT on the modulation of orofacial pain. RESULTS: In this review, we concisely review how 5-HT mediates orofacial pain, how 5-HT is regulated and how we can translate these findings into clinical applications for the prevention and/or treatment of orofacial pain. CONCLUSIONS: 5-HT plays a key role in the modulation of orofacial pain, implying that 5-HT modulators may serve as effective treatment for orofacial pain. However, further research on the precise mechanisms underlying the modulation of orofacial pain is still warranted.

Saliva and tongue microbiota in burning mouth syndrome: An exploratory study of potential roles.

OBJECTIVES: Burning mouth syndrome (BMS) is a chronic orofacial pain disorder with unclear etiology, in which the tongue is most commonly affected. This study aims to provide implication of the possible relationship between oral microbiota and the pathogenesis of BMS. MATERIALS AND METHODS: Saliva and tongue swabs of 15 primary BMS patients and 10 healthy controls were collected and assessed by 16S rRNA gene amplicon sequencing. The microbiota compositions were compared and bioinformatic analysis was conducted. RESULTS: Differences in microbiota compositions between BMS patients and healthy controls were revealed in both saliva and tongue samples. In saliva, Streptococcus, Rothia, and Neisseria were the predominant genus at the taxonomic level in BMS patients. In tongue samples, Prevotella, Streptococcus, and Neisseria were the dominant genus at the taxonomic level in BMS patients. LEfSe analysis and linear discriminant analysis score showed that Actinobacteria were the predominant phylum in saliva, and Selenomonas were enriched in the dorsum of the tongue of BMS patients. CONCLUSIONS: This study for the first-time reported saliva and tongue microbiota profiles were distinguished from that of healthy controls, indicating a necessity for further research on the possible relationship between oral microbes and the pathogenesis of BMS.

Obstructive sleep apnea treatment improves temporomandibular disorder pain.

PURPOSE: The existence of a bidirectional relationship between poor sleep and pain intensity has been studied, and good sleep quality has been found to be a key factor underlying pain control. The purpose of this prospective cohort study was to observe if OSA treatment provides a reduction in temporo-mandibular disorder (TMD) pain and headache attributed to TMD in patients with obstructive sleep apnea (OSA) after 18 months of OSA treatment. METHODS: A prospective cohort study was conducted on consecutive patients suffering from OSA. Patients underwent polysomnography and TMD examination according to the DC/TMD protocol at baseline and after 18 months. Intensity of TMD pain and headache attributed to TMD were analyzed. RESULTS: Of 40 patients (31 men, mean age 51.3 ± 10.3 years), 33 underwent OSA treatment. At the follow-up examination after 18 months, significant improvements in the intensity of pain-related TMD and headache attributed to TMD were observed (p < 0.05). Seven patients did not start treatment for OSA or discontinued treatment. These patients did not show any significant difference in intensity of TMD-pain or headache attributed to TMD after 18 months (p > 0.05). CONCLUSIONS: Significant reductions in intensity of pain-related TMD and headache attributed to TMD were observed in patients with OSA after 18 months of OSA treatment onset, while no difference was observed in subjects not undergoing or discontinuing OSA treatment. TRIAL REGISTRATION: The protocol was registered on ClinicalTrials.gov database with number NCT04948541.

Anxiety, pain catastrophizing, and pain outcomes among older adults with chronic orofacial pain.

Although chronic orofacial pain (COFP) is common among older adults, the role of psychological factors in pain outcomes among this population has received limited attention. This study examined the role of anxiety and pain catastrophizing, two corelates of pain in other populations, in pain intensity and interference among 166 older adults with COFP (79% female, Mage = 68.84, SD = 5.56). Participants completed an online survey including measures of anxiety, pain catastrophizing, and pain intensity/interference. We applied mediation analyses to test indirect associations between anxiety and pain outcomes via pain catastrophizing. Results indicated that anxiety was positively associated with pain intensity and pain interference (bs = .70-1.12, ps < .05). There was also an indirect association between anxiety and pain interference through pain catastrophizing (b = .35, 95% CI [.0383, .7954]), indicating pain catastrophizing partially accounts for this relationship. Assessing and addressing anxiety and pain catastrophizing has the potential to improve treatment outcomes in this population.

Craniocervical Pain, Sleep Quality, Depressive Symptoms, and Physical Activity in Healthcare Workers During COVID-19 Pandemic.

BACKGROUND: An increase in the workload and use of personal protective equipment by healthcare workers was observed during the COVID-19 pandemic. Due to the connections between craniocervical structures, symptoms such as neck pain and temporomandibular symptoms could be influenced by the use of PPE. AIMS: To assess the prevalence of craniocervical pain, sleep quality, physical activity, and depressive symptoms and relationship among craniocervical symptoms in healthcare workers before and during the COVID-19 pandemic in Brazil. DESIGN: Cross-sectional study. PARTICIPANTS: Healthcare workers. SETTINGS: An online questionnaire included a self-report of craniocervical pain intensity [orofacial pain, neck pain, and headache (Numerical Rating Scale)], sleep quality (Pittsburgh Sleep Quality Index), depressive symptoms (Patient Health Questionnaire two items) and physical activity (self-report). METHODS: The sample analysis was performed by descriptive statistics, the paired t-test was used to compare symptoms intensity before and during the pandemic. The relationship between dependent and independent samples was assessed through McNemar test, Pearson's chi-squared test, and Student's independent t-test. A value of p < .05 was adopted as statistical significance. RESULTS: Overall, 147 participants replied the questionnaires. Headache, neck pain, and orofacial pain complaints increased during the pandemic in healthcare workers (p < 0.001). Craniocervical pain was correlated with poor sleep quality, probable depression, and physical activity during the pandemic (p < 0.05). CONCLUSION: Healthcare workers self-reported more craniocervical pain during the COVID-19 pandemic compared to before the pandemic. In addition, poor sleep quality, depressive symptoms, and physical inactivity were associated with craniocervical symptoms during this period.

Are orofacial pain and xerostomia associated with differences in diet, sensory perception, appetite and enjoyment of eating?-An explorative study.

BACKGROUND: Orofacial function is believed to influence an individual's diet. knowledge on appetite and enjoyment of eating in orofacially impaired individuals is scarce. OBJECTIVE: We aimed to explore potential associations between impaired orofacial function, that is, orofacial pain, jaw function limitation and xerostomia, respectively, and diet, appetite, taste perception, as well as the enjoyment of eating. METHODS: An online questionnaire was shared among Aarhus University's dental patients and through social media. A convenience sample of 351 individuals responded (97 men, 254 women, aged 18-86 years). Participants were divided into groups with and without orofacial pain or xerostomia based on responses. Questions about food intake, appetite, meal-related well-being and oral/general health were included. Data were analysed using Mann Whitney U tests, Spearman's correlation, Chi-square tests, and t-tests. RESULTS: Participants with (n = 123) and without (n = 228) orofacial pain differed significantly regarding age, perceived oral/general health, frequency of consumption of for example cooked vegetables and raw whole fruit, perception of sourness, chewiness, and nausea/pain when eating (p ≤ .031). Participants with (n = 101) and without (n = 250) xerostomia differed significantly regarding perceived oral/general health, intake of prepared fruit, alcohol, ice cream/mousse/pudding, general appetite, intake of breakfast and liquid snacks, nausea/pain when eating, taste and chewiness of food (p ≤ .038). CONCLUSION: Diet, appetite, taste and sensory perception, as well as enjoyment of eating of individuals reporting orofacial pain and/or xerostomia differed slightly to that of individuals free of such symptoms. However, due to the explorative nature of this study, the results should be interpreted with caution pending further research on potential long-term effects on nutritional status and well-being.

Awake bruxism in temporomandibular disorders patients referred to tertiary care: A retrospective study on its assessment and TMD management.

BACKGROUND: Bruxism is defined as a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. Bruxism can occur during sleep (sleep bruxism, SB) or during wakefulness (awake bruxism, AB). To date, the effect of AB on the purported negative consequences of bruxism has remained unclear. OBJECTIVES: The assessment of AB, its relation to temporomandibular disorders (TMD) treatment modalities, and their possible outcomes were investigated among TMD patients resistant to treatment in primary care and referred to a tertiary care clinic. METHODS: The records of 115 patients were studied. Patients were referred to the Head and Neck Centre, Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, for TMD treatment between 2017 and 2020. The data derived from the eligible patients' records included the following: background data (age and sex), referral data (reason and previous treatment), medical background (somatic and psychiatric), clinical and possible radiological diagnoses at a tertiary care clinic, treatment modalities for masticatory muscle myalgia, bruxism assessment, its possible treatment modalities and their outcomes, and overall management outcome. We analysed the outcomes of single treatment modalities and combined groups of modalities. For the demographic data, the Chi-squared test and Fischer's Exact test were used to determine the associations between the categorical variables. A Sankey-diagram was used to describe the flow of treatment. RESULTS: Temporomandibular joint-pain-dysfunction syndrome (K07.60) was the most frequent single reason to refer a patient to tertiary care (17.4%). At referral, men had myalgia (M79.1) significantly more often (p = .034) than women. Similarly, men had depression (p = .002) more often and other psychiatric diagnoses (p = .034). At tertiary care, the presence of AB was assessed in 53.9%, and self-reported AB was recorded in 48.7%. In patients with possible AB, those who were prescribed neuropathic pain medication showed significantly less improvement in symptoms (p = .021) than those who underwent splint therapy (p = .009). Overall, half of the patients showed overall improvement in their TMD symptoms from the treatment combinations. CONCLUSION: Despite several treatment modalities, only half of the patients showed improvement in their symptoms in the present study. A standardised assessment method encompassing all factors contributing to bruxism behaviours and their consequences is suggested.

Role of neuropeptides in orofacial pain: A literature review.

BACKGROUND: Neuropeptides play a critical role in regulating pain and inflammation. Despite accumulating evidence has further uncovered the novel functions and mechanisms of different neuropeptides in orofacial pain sensation and transmission, there is deficient systematic description of neuropeptides' pain modulation in the orofacial region, especially in the trigeminal system. OBJECTIVES: The present review aims to summarise several key neuropeptides and gain a better understanding of their major regulatory roles in orofacial inflammation and pain. METHODS: We review and summarise current studies related to calcitonin gene-related peptide (CGRP), substance P (SP), opioid peptide (OP), galanin (GAL) and other neuropeptides' functions and mechanisms as well as promising targets for orofacial pain control. RESULTS: A number of neuropeptides are clearly expressed in the trigeminal sensory system and have critical functions in the transduction and pathogenesis of orofacial pain. The functions, possible cellular and molecular mechanisms have been introduced and discussed. Neuropeptides and their agonists or antagonists which are widely studied to be potential treatment options of orofacial pain has been evaluated. CONCLUSIONS: Various neuropeptides play important but distinct (pro-nociceptive or analgesic) roles in orofacial pain with different mechanisms. In summary, CGRP, SP, NPY, NKA, HK-1, VIP mainly play proinflammatory and pro-nociceptive effects while OP, GAL, OXT, OrxA mainly have inhibitory effects on orofacial pain.

Incidence, diagnosis, and management of orofacial pain among new patients receiving tertiary care in Thailand: A 6-year retrospective study comparing before and during the COVID-19 outbreak.

BACKGROUND: There is insufficient data on orofacial pain related to the COVID-19 outbreak in Thailand. OBJECTIVE: To investigate the incidence, diagnosis and management of orofacial pain among new patients over the last 6 years, before and during the COVID-19 outbreak. METHODS: Medical records from new patients who first visited Chulalongkorn Dental Hospital between 2017 and 2022 were retrospectively investigated. The sample size was determined, and proportional stratified random sampling was employed to distribute the sample number proportionally across each year. The hospital number of each patient was randomised using online software as a sampling strategy. A data collection form was developed and used to gather information from the digital data system. RESULTS: At the first visit, 770 out of 1359 patients (56.7/100 people, 95% CI: 54.0-59.3) reported orofacial pain defined as acute, chronic and unclassified pain. The most common chief complaints based on the AAOP classification were odontogenic pain (90.00%) and temporomandibular disorders (6.10%). The top three provisional modified ICD-10-TM diagnoses among these patients were pulp diseases (21.95%), impacted teeth (20.65%) and dental caries (9.09%). 81.87% of dental students' provisional diagnoses matched the final diagnoses given by dental specialists. Only 63.38% of orofacial pain patients were completely managed during the COVID-19 pandemic with common procedures being surgical removal, extraction and root canal therapy. CONCLUSION: Half of Thai dental patients seeking tertiary care at a university dental hospital reported orofacial pain, which was not impacted by the COVID-19 pandemic. In contrast, dysfunction-related problems in the orofacial area significantly increased during the pandemic.

What has a year of social isolation due to the COVID-19 pandemic influenced oral parafunctional habits and temporomandibular disorders? A case-control study.

OBJECTIVE: Few studies investigated the influence of oral parafunctional habits during the COVID-19 pandemic. Since some studies have demonstrated that signs and symptoms of temporomandibular disorder (TMD), as well as psychological alterations, increased during the COVID-19 pandemic lockdown, the aim of this study was to investigate whether social isolation is a situation that increases the prevalence of oral parafunctional habits. METHODS: This was an observational case-control study. An online survey with questions about TMD symptoms (Diagnostic Criteria Symptom Questionnaire) and oral parafunctional habits (Oral Behaviours Checklist [OBC]) was administered to Brazilian residents at two different times (2020 and 2021). The participants were divided according to social isolation practices into study groups (GI: 2020, n = 507; GIII: 2021, n = 282) and control groups (GII: 2020, n = 98; GIV: 2021, n = 202). RESULT: In each group, we evaluated the association of the frequency of oral parafunctional habits with the symptoms of TMD, and we observed that individuals with a greater presence of painful TMD present a greater number of oral parafunctional habits. Despite the literature showing that individuals who practiced social isolation developed more oral parafunctional habits, when analysing the association of the OBC questions in Groups GI × GII and GIII × GIV, only 'sustained talking' (p = .0022) and 'hold telephone between your hand and shoulders' (p = .0124) showed a significant difference in GI × GII. Kendall's coefficient of concordance revealed that there was a very strong concordance (GI × GII 0.9515 (p = .0087) and GIII × GIV 0.9655 (p = .0074)) between the ranks of the analysed oral parafunctional habits in all groups. CONCLUSION: We can state that Individuals who practiced social isolation did not present more oral parafunctional habits than individuals who did not.

Treatment approaches, outcomes and prognostic indicators in patients with tinnitus and temporomandibular disorders evaluated with DC/TMD: A systematic review and Meta-analysis.

OBJECTIVE: This systematic review summarised the results reported in randomised controlled trials (RCTs) aimed at evaluating the different treatment approaches in patients with tinnitus associated with temporomandibular disorders (TMD) evaluated with the diagnostic criteria of temporomandibular disorders (DC/TMD), and the possible predictive factors influencing treatment outcomes. METHODS: The electronic databases Medline, Web of Science, Latin American and Caribbean Health Sciences Literature (LILACs) were searched systematically up to March 2023. Only RCTs with full texts were included in this study. The eligibility of the RCTs selected was based on the PICO model (participants, intervention, comparators, outcomes), and subjects of any age, sex or ethnicity, were included when showing both tinnitus and TMD, diagnosed through DC/TMD criteria. RESULTS: From a total of 635 articles, only five RCTs were included and the data from a total of 329 participants were examined. Two RCTs focused on the efficacy of the multidisciplinary approach among people with tinnitus who have TMD; two RCTs examined prognostic indicators predicting a positive outcome after multidisciplinary orofacial treatment; one RCT analysed low-level laser therapy's effectiveness with Nd:YAG laser. CONCLUSION: A multidisciplinary non-invasive approach is the most efficacious treatment for tinnitus in patients diagnosed with TMD. Baseline tinnitus severity, gender, quality of life, age, and tinnitus duration were considered predictive factors of clinical outcomes in patients diagnosed with DMTs and referring tinnitus.

Visual psychosocial profiling of Chinese temporomandibular disorder pain patients and correlations with somatosensory function.

BACKGROUND: Psychosocial function of Chinese temporomandibular disorders (TMD) pain patients and the correlation with somatosensory function has not been sufficiently studied. OBJECTIVE: The study aims at assessing the psychosocial function of Chinese TMD pain patients by visualisation method and evaluating the correlations with somatosensory function quantitatively. METHODS: The Symptom Checklist 90 (SCL-90) questionnaire and standardised quantitative sensory testing (QST) were administered to 70 Chinese TMD pain patients and age- and gender-matched healthy controls (HCs). Of these, 40 TMD arthralgia patients received QST before and after medication. Psychosocial and somatosensory parameters were transformed into standardised scores. Differences within groups were assessed through t tests. Correlations between psychosocial and somatosensory profiles were explored through correlation analyses with Bonferroni correction for multiple comparisons. RESULTS: 100% of the Chinese TMD pain patients exhibited psychosocial distress in contrast to HCs. Anger and hostility showed negative correlation with the thermal nonnociceptive parameter (thermal sensory limen, p =.002) and nociceptive parameters (cold pain threshold and pain pressure threshold, p<.001). Correlation analysis indicated that cold detection threshold was negatively correlated with somatization and mechanical pain sensitivity had a negative correlation with anger and hostility through medical treatment (p <.001). CONCLUSIONS: Visual psychosocial profiles provided an easy overview of psychosocial function in Chinese TMD pain patients. Anger and hostility was associated with increased thermal nonnociceptive and nociceptive sensitivity to stimuli. Psychosocial distress might be negatively associated with TMD treatment response which indicated a possible need for psychological intervention during treatment.

Predictors of patients' satisfaction after temporomandibular disorder treatment in a referral clinic.

BACKGROUND: Evaluating patients' satisfaction after received care for temporomandibular disorders (TMD) pain provides oral health care professionals with knowledge and tools to improve their clinical procedures. However, knowledge on patient characteristics that determine satisfaction with the received care for TMD pain is lacking. OBJECTIVE: To identify potential baseline predictors for patients' satisfaction regarding the management of TMD pain upon treatment completion in a referral clinic. METHODS: Eligible patients, viz., individuals of ≥16 years of age, with a TMD-pain diagnosis according the diagnostic criteria for TMD (DC/TMD), and who were treated in a referral clinic, were included. As part of their standard care, a set of diagnostic questionnaires was filled in (e.g. TMD-pain screener, graded chronic pain scale (GCPS), etc.). After completion of the received care, patients filled in a custom-made questionnaire based on patient reported experience measures (PREMs) to quantify their satisfaction with their treatment results and received care. To identify potential predictors associated with patients' satisfaction, univariate and multivariate linear regression analyses were used. RESULTS: Twenty-seven patients (mean 39.6, SD 15.0) were included in this study. Overall, the patients were satisfied with the treatment results and the received care. Depressive feelings were negatively associated with satisfaction of treatment results (p = .01) and positively associated with satisfaction of received care (p = .01), while pain intensity was negatively associated with satisfaction of the received care. CONCLUSION: Depressive feelings are a significant negative predictor of patients' satisfaction with the treatment result for TMD pain, while average pain intensity is a significant negative predictor of patients' satisfaction with the received care.

Association between oxidative stress and chronic orofacial pain and potential druggable targets: Evidence from a Mendelian randomization study.

BACKGROUND: Oxidative stress indicators affect chronic orofacial pain (COFP), but how to reduce these effects is uncertain. OBJECTIVES: 11 oxidative stress biomarkers were collected as exposures, while four forms of COFP were chosen as outcomes for Mendelian randomization (MR) study. METHODS: The effect estimates between oxidative stress and COFP were calculated using inverse variance-weighted MR (IVW-MR). Then, functional mapping and annotation (FUMA) was utilized in order to carry out SNP-based functional enrichment analyses. In addition, the IVW-MR method was applied to combine effect estimates when using genetic variants associated with oxidative stress biomarkers as an instrument for exploring potential druggable targets. RESULTS: The results indicated that oxidative stress biomarkers (causal OR of uric acid (UA), 0.998 for myofascial pain, 95% CI 0.996-1.000, p < .05; and OR of glutathione transferase (GST), 1.002 for dentoalveolar pain, 95% CI 1.000-1.003, p < .05) were significantly linked with the probability of COFP. Functional analysis also demonstrated that UA and myofascial pain genes were prominent in nitrogen and uracil metabolism, while GST and dentoalveolar pain genes were enriched in glutathione metabolism. Also, the study provided evidence that solute carrier family 2 member 9 (SLC2A9) and glutathione S-transferase alpha 2 (GSTA2) cause discomfort in the myofascial pain (OR = 1.003, 95% CI 1.000-1.006; p < .05) and dentoalveolar region (OR = 1.001, 95% CI 1.000-1.002; p < .05), respectively. CONCLUSIONS: In conclusion, this MR study indicates that genetically predicted myofascial pain was significantly associated with decreased UA and dentoalveolar pain was significantly associated with increased GST level. SLC2A9 inhibitor and GSTA2 inhibitor were novel chronic orofacial pain therapies and biomarkers, but clinical trials are called to examine if these oxidative biomarkers have the protective effect against orofacial pain, and further research are needed to explore the underlying mechanisms.

Temporomandibular joint rehabilitative approaches for children and adolescents affected by juvenile idiopathic arthritis: A systematic review.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, and temporomandibular joints (TMJs) are involved in 39%-78% of patients. AIM: The aim of this systematic review was to assess the effectiveness of conservative approaches in improving TMJ arthritis in children and adolescents affected by JIA. DESIGN: PubMed, Scopus, and Web of Science were systematically searched from the inception until February 25, 2024, to identify observational studies presenting participants with a diagnosis of JIA affecting the TMJ, rehabilitative approaches for TMJ arthritis as interventions, and clinical or radiological assessment of TMJ arthritis as outcome. RESULTS: Of 478 papers suitable for title/abstract screening, 13 studies were included. The studies evaluated the effectiveness of intra-articular (IA) corticosteroid (CS) injections, IA infliximab injections, arthrocentesis alone or in combination with IACS injections, occlusal splint, functional appliance, and physiotherapy. The effectiveness of IACS injections was shown in eight studies. IA infliximab injections did not appear to significantly improve TMJ arthritis. CONCLUSION: Results of this systematic review suggested that conservative treatments, especially IACS injections, might be effective in improving TMJ arthritis in patients affected by JIA. Further studies with a higher level of evidence and more representative samples should be conducted.

Prevalence of orofacial pain in individuals with mild cognitive impairment or dementia: A systematic review and meta-analysis.

BACKGROUND: This systematic review investigated the prevalence of orofacial pain in patients with mild cognitive impairment (MCI) or dementia. MATERIALS AND METHODS: The search was conducted in five databases (Medline (Ovid), Embase (Ovid), CINAHL, Scopus and LILACS), in three grey literature sources and in included articles' reference lists. Three independent reviewers performed study selection, quality appraisal and data extraction. The risk of bias was assessed with the National Institutes of Health tool. Prevalence was calculated using the random-effects model. Subgroup analysis and meta-regression were used to explore the heterogeneity of results. RESULTS: The database and grey literature search led to 12 246 results, from which nine studies were included; a further four were selected through citation searching. The total sample comprised 6115 patients with dementia and 84 with MCI. All studies had high risk of bias. The overall estimated pooled prevalence of orofacial pain among dementia participants was 19.0% (95% CI, 11.0%-27.0%; I2 , 97.1%, P < .001). Only one study included MCI participants, among which the prevalence of orofacial pain was 20.5%. Subgroup analysis demonstrated that the different sources of diagnosis might explain the heterogeneity. A higher prevalence of orofacial pain was observed in dementia participants aged over 80 years or living in nursing homes. Meta-regression analysis showed a nonlinear relationship between age and the prevalence of orofacial pain. CONCLUSIONS: The pooled data from the primary studies revealed that 2 out of 10 patients with dementia have orofacial pain. Further research is needed to clarify the magnitude in individuals with MCI.

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.