Temporomandibular Joint Disorder Pain Research Articles

Effects of botulinum toxin type A in patients with painful temporomandibular joint disorders: A systematic review and meta-analysis

Objective: To assess the therapeutic efficacy of botulinum toxin type A (BTX-A) for managing myofascial pain related to temporomandibular disorders (TMDs). Methods: This study was conducted according to the PRISMA 2020 statement guidelines. The PubMed, Embase, and Cochrane Library databases were searched. Only randomized controlled trials (RCTs) were included. The primary outcome was pain score on the visual analogue scale (VAS), and the secondary outcomes were maximum mouth opening (MMO) and adverse effects. The Cochrane risk of bias tool was used to assess risk bias. A meta-analysis of studies with the same interventions, controls, assessment methods and follow-up durations was performed. Results: A total of 519 studies were retrieved, of which 20 RCTs were included in the qualitative analysis and 6 were included in the meta-analysis. The results showed that, compared with placebo, BTX-A injection was more effective at relieving myofascial pain, and its effect was similar to that of conventional methods. However, there was no difference in MMO between the two groups. After study assessment with the RoB 2.0 tool, six studies showed a low risk of bias, 13 studies showed some concerns regarding the reported results, and only one study showed a high risk of bias. Adverse effects of BTX-A injection were observed in four studies. Conclusions: In conclusion, BTX-A is effective at relieving pain in TMD patients but does not improve mouth opening. To minimize adverse effects, we recommend a low dose of BTX-A for TMD patients who do not experience complete pain relief from conservative treatments.

Effect of pain on cranio-cervico-mandibular function and postural stability in people with temporomandibular joint disorders.

Neck and jaw pain is common and is associated with jaw functional limitations, postural stability, muscular endurance, and proprioception. This study aimed to investigate the effect of jaw and neck pain on craniocervico- mandibular functions and postural stability in patients with temporomandibular joint disorders (TMJDs). Fifty-two patients with TMJDs were included and assessed using Fonseca's Questionnaire and the Helkimo Clinical Dysfunction Index. An isometric strength test was performed for the TMJ depressor and cervical muscles. The TMJ position sense (TMJPS) test and cervical joint position error test (CJPET) were employed for proprioception. Total sway degree was obtained for the assessment of postural stability. Deep neck flexor endurance (DNFE) was assessed using the craniocervical flexion test. The mandibular function impairment questionnaire (MFIQ) was employed to assess mandibular function, and the craniovertebral angle (CVA) was measured for forward head posture. Jaw and neck pain negatively affected CVA (R2 = 0.130), TMJPS (R2 = 0.286), DNFE (R2 = 0.355), TMJ depressor (R2 = 0.145), cervical flexor (R2 = 0.144), and extensor (R2 = 0.148) muscle strength. Jaw and neck pain also positively affected CJPET for flexion (R2 = 0.116) and extension (R2 = 0.146), as well as total sway degree (R2 = 0.128) and MFIQ (R2 = 0.230). Patients with painful TMJDs, could have impaired muscle strength and proprioception of the TMJ and cervical region. The jaw and neck pain could also affect postural stability, and the endurance of deep neck flexors as well as mandibular functions in TMJDs.

Mitochondria-targeting nanozyme alleviating temporomandibular joint pain by inhibiting the TNFα/NF-κB/NEAT1 pathway.

Inflammatory cytokines that are secreted into the spinal trigeminal nucleus caudalis (Sp5C) may augment inflammation and cause pain associated with temporomandibular joint disorders (TMD). In a two-step process, we attached triphenylphosphonium (TPP) to the surface of a cubic liposome metal-organic framework (MOF) loaded with ruthenium (Ru) nanozyme. The design targeted mitochondria and was designated Mito-Ru MOF. This structure scavenges free radicals and reactive oxygen species (ROS) and alleviates oxidative stress. The present study aimed to investigate the effects and mechanisms by which Mito-Ru MOF ameliorates TMD pain. Intra-temporomandibular joint (TMJ) injections of complete Freund's adjuvant (CFA) induced inflammatory pain for ≥10 d in the skin areas innervated by the trigeminal nerve. Tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1), and ROS also have been proved to be significantly upregulated in the Sp5C of TMD mice. Moreover, a single Mito-Ru MOF treatment alleviated TMD pain for 3 d and downregulated TNF-α, NF-κB, lncRNA NEAT1, and ROS. NF-κB knockdown downregulated NEAT1 in the TMD mice. Hence, Mito-Ru MOF inhibited the production of ROS and alleviated CFA-induced TMD pain via the TNF-α/NF-κB/NEAT1 pathway. Therefore, Mito-Ru MOF could effectively treat the pain related to TMD and other conditions associated with severe acute inflammatory activation.

Impact of different types of temporomandibular disorders on jaw functional limitation and psychological distress in orthodontic patients.

Some orthodontic patients are associated with temporomandibular joint disorders (TMDs), and the differences between jaw function and psychological states in orthodontic patients with different types of TMDs remain unknown. This cross-sectional study aimed to investigate the prevalence of different types of TMDs in orthodontic patients and to evaluate the relationship between different types of TMDs and jaw functional limitation and psychological distress in orthodontic patients. A questionnaire was sent to patients willing to participate in this survey, which included questions about the demographic characteristics of the participants, the five TMD symptoms (5Ts) of the Diagnostic Criteria for TMDs, the Jaw Functional Limitation Scale-8 (JFLS-8) and the Patient Health Questionnaire for Depression and Anxiety (PHQ-4). The subjects were divided into three groups: painful TMDs (PT), non-painful TMDs (NPT), and TMD-free according to whether they had TMDs and its subtypes. A total of 670 valid questionnaires were collected from 182 males and 488 females. The prevalence of TMDs was 35.4%, of which the prevalence of PT was 11.8% and the prevalence of NPT was 23.6%. The median JLFS-8 score of TMD patients was significantly higher than TMD-free, and PT patients were significantly higher than NPT (p = .026). After adjusting for confounding factors, the jaw function and psychological states of PT patients and NPT patients were worse than those of the TMD-free group. Among the orthodontic patients surveyed, more than one-third had TMDs and the prevalence of PT was lower than NPT. Having TMDs is associated with more severe jaw functional limitation, and PT patients were more serious than NPT patients. At the same time, the psychological states of TMDs patients were also worse.

Temporomandibular joint disorders prevalence and health-seeking preferences among Al-Madinah community: A prospective cross sectional study

Background: Painful temporomandibular joint disorders (TMDs) are of musculoskeletal origin and are considered the most common cause of non-odontogenic pain in the orofacial region. The purpose of this study was to investigate the prevalence and awareness of temporomandibular joint (TMJ) disorders in Almadinah Almunawwarah community. Methods: A prospective observational cross-sectional study with convenience sampling was conducted. The patients were selected from the dental college and the hospital at Taibah University in Al-Madinah, Saudi Arabia. A translated Arabic version of Fonseca's questionnaire was employed. The questionnaire asked about the participant's personal information, if they thought they had TMDs, and who to visit for therapy if necessary. These were followed by 10 items from Fonseca's questionnaire, each with a three-point scale. Results: The questionnaire was completed by 518 people. Females made up 57.1% of the participants. TMDs were present in 61% of the population, with varying degrees of severity. Males (44.3%) were less affected than females (55.7%). The difference, however, was not statistically significant (P = 0.354). Out of the 61% TMDs Positive patients, 74.1% had mild TMDs symptoms, while 20.8% and 5.1%, respectively, had moderate and severe TMDs symptoms (P = 0.05). The severity of the symptoms was unaffected by demographic data (P > 0.05). Only 40% seek care, with 64.6% selecting for a dentist or orofacial pain specialists for their management and 24.6% preferring for an orthopaedic specialist (P= 0.008). Conclusions: Participants from Al-Madinah had a greater prevalence of mild TMDs. The majority of the participants had no idea who to go to for treatment. The findings of this study highlight the importance of educational activities to enhance public awareness

RNA sequencing profiling of mRNAs, long noncoding RNAs, and circular RNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation.

Patients with temporomandibular joint disorders (TMD) have high levels of inflammatory pain-related disability, which seriously affects their physical and mental health. However, an effective treatment is yet to be developed. Both circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) contribute to regulating pain conduction. In our current study, we report the expression profiles of circRNAs, lncRNAs, and mRNAs in the trigeminal ganglion (TG) associated with complete Freund’s adjuvant (CFA)-induced TMD inflammation pain. The collected TGs from the experimental (CFA) and control (saline) groups were processed for deep RNA sequencing. Overall, 1078,909,068 clean reads were obtained. A total of 15,657 novel lncRNAs were identified, where 281 lncRNAs were differentially expressed on CFA3D and 350 lncRNAs were differentially expressed on CFA6D. In addition, a total of 55,441 mRNAs and 27,805 circRNAs were identified, where 3,914 mRNAs and 91 circRNAs were found differentially expressed, between the CFA3D and saline groups, while 4,232 mRNAs and 98 DE circRNAs were differentially expressed between the CFA6D and saline groups. Based on functional analyses, we found that the most significant enriched biological processes of the upregulated mRNAs were involved in the immunity, neuron projection, inflammatory response, MAPK signaling pathway, Ras signaling pathway, chemokine signaling pathway, and inflammatory response in TG. Further analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway suggest the involvement of dysregulated genes in the pain occurrence mechanism. Our findings provide a resource for expression patterns of gene transcripts in regions related to pain. These results suggest that apoptosis and neuroinflammation are important pathogenic mechanisms underlying TMD pain. Some of the reported differentially expressed genes might be considered promising therapeutic targets. The current research study revealed the expression profiles of circRNAs, lncRNAs, and mRNAs during TMD inflammation pain and sheds light on the roles of circRNAs and lncRNAs underlying the pain pathway in the trigeminal system of TMD inflammation pain.

Temporomandibular joint disorders prevalence and awareness of appropriate clinical practices, among Al-Madinah community: A prospective cross sectional study

Background: Painful temporomandibular joint disorders (TMDs) are of musculoskeletal origin and are considered the most common cause of non-odontogenic pain in the orofacial region. The purpose of this study was to investigate the prevalence and awareness of temporomandibular joint (TMJ) disorders in Almadinah Almunawwarah community. Methods: A prospective observational cross-sectional study with convenience sampling was conducted. A translated Arabic version of Fonseca's questionnaire was employed. The questionnaire asked about the participant's personal information, if they thought they had TMDs, and who to visit for therapy if necessary. These were followed by 10 items from Fonseca's questionnaire, each with a three-point scale. Results: The questionnaire was completed by 598 people. Females made up 57.1% of the participants. TMDs were present in 61% of the population, with varying degrees of severity. Males (44.3%) were less affected than females (55.7%). The difference, however, was not statistically significant (P = 0.354). Out of the 61% TMDs Positive patients, 74.1% had mild TMDs symptoms, while 20.8% and 5.1%, respectively, had moderate and severe TMDs symptoms (P = 0.05). The severity of the symptoms was unaffected by demographic data (P > 0.05). Only 40% seek care, with 64.6% selecting for a dentist and 24.6% preferring for an orthopaedic specialist (P= 0.008). Conclusions: Participants from Al-Madinah had a greater prevalence of mild TMDs. The majority of the participants had no idea who to go to for treatment. The findings of this study highlight the importance of educational activities to enhance public awareness

Nonpharmacological Interventions for Pain in Patients with Temporomandibular Joint Disorders: A Systematic Review.

This systematic review aimed to compare the efficacy of nonpharmacological therapies for painful temporomandibular joint disorders. The protocol was registered on International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42020171364). The search was performed on the electronic databases PubMed, Google Scholar, Clinical Trials, and Web of Science. The eligibility criteria were randomized controlled trials in patients diagnosed with painful temporomandibular joint disorders comparing the pain relief between conventional treatment and nonpharmacological therapies such as acupuncture, physiotherapy, low-level laser, and massage. Fourteen articles were included in this review. At the overall bias of the studies included, 71.42% exhibited some concerns and 28.57% had high risk. The efficacy of nonpharmacological interventions was found to be moderate in the short term and variable in the long term for pain reduction in patients with temporomandibular joint disorders. The evidence pointed out that acupuncture, laser therapy, and physiotherapy are potentially useful interventions for pain relief in patients with temporomandibular joint disorders. However, there is a lack of consistency and short-term follow-up in the studies to determine the lasting of such effect.

MMPs in tissues retrieved during surgery from patients with TMJ disorders relate to pain more than to radiological damage score.

Orofacial pain is among the most common chronic pain conditions and can result from temporomandibular disorders (TMDs) of the temporomandibular joint (TMJ). Matrix metalloproteinases (MMPs) drive degeneration of TMJ tissues and likely mediate pain in TMJ disorders given their role in nociception. However, few studies have assessed MMPs in the TMJ innervated tissues nor in the context of pain. This study defined the extent of MMP-1, MMP-9, and MMP-2 in TMJ tissues from patients undergoing total joint replacement (TJR) or arthroplasty discectomy for painful TMJ disorders. Protein expression was probed by Western blot in TMJ disc and capsular ligaments taken during TJR (n = 6) or discectomy (n = 3) for osteoarthritis or internal derangement in an IRB-approved study. Pro- and active MMP-1, active MMP-9, and pro- and active MMP-2 are detectable. MMP-1 and MMP-9 correlate positively to each other (Kendall's τ = 0.63;p = 0.01), strengthening the hypothesis that they are mechanistically related in regulatory cascades. Active MMP-1 and active MMP-9 correlate positively with self-reported pain scores (τ ≥ 0.51; p ≤ 0.04), suggesting their involvement in peripheral nociception. Overall, neither MMPs nor pain correlatewith the functional vertical opening of the jaw. MMP-1 varies with the observed stage of degeneration during surgery (p = 0.04). Neither overall MMPs nor pain correlatewith the overall magnetic resonance imaging scores, corroborating the longstanding, but confounding, clinical observation that pain and radiological evidence of joint damage are not always related. Clinical significance: These findings suggest that MMPs mediate pain in innervated soft tissues and may be targets for diagnosing disease stage and treatments in painful TMJ disorders.

Occlusal Adjustment vs Placebo for Chronic Temporomandibular Disorders. The MAP Randomized Clinical Trial

Importance: Evidence regarding effective treatments for temporomandibular joint disorders (TMDs) is limited. Objective: To determine whether occlusal adjustment may reduce the pain intensity of patients with chronic TMD. Design: The MAP study was a phase 3 randomized, participant- and assessor-blinded, placebo-controlled trial of a novel occlusal therapy for chronic TMD over the course of 6 months. It was carried out from August 4, 2014 to October 25, 2018 (last 6-month follow-up). Setting: Single referral tertiary care hospital. Therapies were performed in a University Clinic in a different city. Participants: From 924 adult patients screened diagnosed as TMD, 820 were excluded (partial tooth loss, no chronic condition, malocclusion); 27 declined to participate. Seventy-seven participants underwent randomization; all but one female participant completed the analysis. Interventions: Participants were randomly (1:1) assigned to occlusal adjustment therapy (N=39) or similar placebo (N=38) that did not remove any enamel. Main Outcome and Measure: Primary outcome (before data collection began): change in pain score (in a 0-10 points visual analogue scale) from baseline to the 3- and 6-month assessments. Because one majority of the 1-month therapy visits (carried out in a city 70 km away) were delayed nearest the 3-month visit, the actual primary outcome was the average pain intensity improvement at 6 months in respect of the baseline scores (05/05/2016 ISRCTN amendment). Clinical important difference 1.5 points. Results: The trial was stopped early for efficacy. This report includes all randomized participants in their originally assigned group: 39 to occlusal adjustment and 38 to placebo therapy. Both groups were balanced regarding baseline characteristics. As compared with the placebo, occlusal adjustment reduced jaw pain intensity (adjusted mean difference, -1.54; 95% confidence interval [CI] -.5 to -2.6; P=0.004; ANCOVA model). Conclusions and Relevance: The occlusal adjustment was effective in treating chronic TMD pain and improved limited mouth opening in comparison with the placebo over a 6-month period. The results of this trial are provisional and should not be generalized to patients with different dental conditions, or if the therapies are provided by less experienced dental professionals.

Changes in the temporomandibular joint clicking and pain disorders after orthognathic surgery: Comparison of orthodontics-first approach and surgery-first approach.

The purposes of this study were to investigate the influence of the orthodontics-first approach (OFA) and surgery-first approach (SFA) on changes in the signs and symptoms of temporomandibular joint disorders (TMDs) and to compare pre- and postoperative orthodontic treatment duration and total treatment duration between the two approaches. This retrospective study recruited 182 adult patients with malocclusions treated with OFA and SFA and recorded variables such as age, gender, skeletal classification, and signs and symptoms of TMD (clicking and pain disorders) before the start of the surgical-orthodontic treatment and after surgery. Changes in the signs and symptoms of TMD and treatment duration were evaluated within each approach and compared between two approaches. A binary logistic regression was performed to assess the influence of the variables on the postoperative signs and symptoms of TMD. There were no significant postoperative changes in temporomandibular joint (TMJ) pain for OFA and SFA, whereas a significant reduction was found in TMJ clicking after surgery for both approaches. According to binary logistic regression, the type of surgical-orthodontic treatment (OFA or SFA) was not a significant risk factor for postoperative TMJ clicking and pain, and the risk of postoperative TMJ clicking and pain was significant only when TMJ clicking (OR = 10.774, p < 0.001) and pain (OR = 26.876, p = 0.008) existed before the start of the entire treatment, respectively. With regard to the treatment duration, SFA (21.1 ± 10.3 months) exhibited significantly shorter total treatment duration than OFA (34.4 ± 11.9 months) (p < 0.001). The results of this study suggest that surgical-orthodontic treatment using SFA can be a feasible option of treatment for dentofacial deformities based on the equivalent effect on TMD and shorter overall treatment period compared to conventional surgical-orthodontic treatment using OFA.

Progesterone and Allopregnanolone Rapidly Attenuate Estrogen-Associated Mechanical Allodynia in Rats with Persistent Temporomandibular Joint Inflammation.

Temporomandibular joint disorder (TMD) is associated with pain in the joint (temporomandibular joint, TMJ) and muscles involved in mastication. TMD pain dissipates following menopause but returns in some women undergoing estrogen replacement therapy. Progesterone has both anti-inflammatory and antinociceptive properties, while estrogen’s effects on nociception are variable and highly dependent on both natural hormone fluctuations and estrogen dosage during pharmacological treatments, with high doses increasing pain. Allopregnanolone, a progesterone metabolite and positive allosteric modulator of the GABAA receptor, also has antinociceptive properties. While progesterone and allopregnanolone are antinociceptive, their effect on estrogen-exacerbated TMD pain has not been determined. We hypothesized that removing the source of endogenous ovarian hormones would reduce inflammatory allodynia in the TMJ of rats and both progesterone and allopregnanolone would attenuate the estrogen-provoked return of allodynia. Baseline mechanical sensitivity was measured in female Sprague–Dawley rats (150–175 g) using the von Frey filament method followed by a unilateral injection of complete Freund’s adjuvant (CFA) into the TMJ. Mechanical allodynia was confirmed 24 h later; then rats were ovariectomized or received sham surgery. Two weeks later, allodynia was reassessed and rats received one of the following subcutaneous hormone treatments over 5 days: a daily pharmacological dose of estradiol benzoate (E2; 50 μg/kg), daily E2 and pharmacological to sub-physiological doses of progesterone (P4; 16 mg/kg, 16 μg/kg, or 16 ng/kg), E2 daily and interrupted P4 given every other day, daily P4, or daily vehicle control. A separate group of animals received allopregnanolone (0.16 mg/kg) instead of P4. Allodynia was reassessed 1 h following injections. Here, we report that CFA-evoked mechanical allodynia was attenuated following ovariectomy and daily high E2 treatment triggered the return of allodynia, which was rapidly attenuated when P4 was also administered either daily or every other day. Allopregnanolone treatment, whether daily or every other day, also attenuated estrogen-exacerbated allodynia within 1 h of treatment, but only on the first treatment day. These data indicate that when gonadal hormone levels have diminished, treatment with a lower dose of progesterone may be effective at rapidly reducing the estrogen-evoked recurrence of inflammatory mechanical allodynia in the TMJ.

The relationship between spinal pain and temporomandibular joint disorders in Korea: a nationwide propensity score-matched study

BackgroundPatients with temporomandibular joint disorder (TMD) often complain of pain in other areas. Several studies have been conducted on spinal pain in TMD patients, but have contained only limited information. Therefore, this study analyzed the relationship between TMD and spinal pain in greater detail by using nationwide data.MethodsA total of 12,375 TMD patients from the Korean National Health Insurance Review and Assessment database were analyzed. Controls were selected using propensity score-matching. The McNemar test, chi-square test, and paired t-test were used to compare the prevalence and severity of spinal pain between cases and matched controls. Logistic regression and linear regression models were used to analyze factors affecting the prevalence and severity of spinal pain in patients with TMD.ResultsThe annual period prevalence of TMD was 1.1%. The prevalence was higher in younger individuals than in individuals of other ages and was higher in women than in men. The medical expenditure for TMD per person was $86. Among TMD patients, 2.5% underwent surgical procedures and 0.3% were hospitalized. The prevalence of spinal pain in patients with TMD was 48%, whereas that in the control group was 34%. Increased severity of TMD was associated with an increased probability of spinal pain. The medical expenditure, mean number of visits, and lengths of treatment for spinal pain were greater for patients with TMD than for controls ($136 vs. $81, 4.8 days vs. 2.7 days, 5.5 days vs. 3.3 days). Higher TMD grade was associated with greater differences in average medical expenditure, number of visits, and lengths of treatment for spinal pain between cases and controls. Additionally, for women, living in a rural area and having an older age and more severe TMD were associated with a greater probability of spinal pain and higher medical expenditure related to spinal pain.ConclusionA strong association was observed between the presence of TMD and the presence of spinal pain. The association became stronger as the severity of TMD increased, indicating a positive correlation between the severity of TMD and spinal pain.

A Phenomenologic Study About the Dietary Habits and Digestive Complications for People Living with Temporomandibular Joint Disorders

To better understand the experiences of individuals who must alter the types of food they eat because of having a chronic temporomandibular joint disorder (TMD) and the digestive issues that these alterations produce. Six participants answered open-ended questions during semi-structured interviews about their experiences with TMD-related changes in diet and digestion. These interviews, held face-to-face with the participants in a nonclinical environment, were recorded and transcribed. Interpretive phenomenology was used to arrange and analyze the narrative data collected. The authors identified three common themes among the participants: (1) constipation and bloating; (2) loss of chewing function; and (3) weight change. For each of these themes, participants expressed physiologic and psychologic complications, which were largely unaddressed by their health care providers. These findings highlight the need for health care providers to establish nutritional guidelines for TMD individuals at risk of physiologic and psychologic comorbidities. Health care intervention programs to treat people living with chronic TMD pain and that provide nutritional guidance will help decrease medical crises and the need for expensive interventions and will better assist these patients.

Peripheral Serotonin Enhances Orofacial Nocifensive Behavior in Female Rats at Lower Doses During Proestrus

Trigeminal pain, such as migraine and temporomandibular joint disorder pain, disproportionately affects women, however the mechanism underlying this dimorphic prevalence is unclear. One pain mechanism that may be modulated by gonadal hormones is the ability of the neurotransmitter serotonin (5HT) to lower pain thresholds. 5HT is a pronociceptive mediator in the periphery where it is stored and released by platelets and immune cells (e.g. mast cells, T‐cells, dendritic cells). The pronociceptive role of 5HT is well‐known in males, however 5HT may be under modulation by gonadal hormones in females. We recently reported that 5HT, injected into the hind paw, evoked greater, longer‐lasting pain behaviors in female rats during proestrus and estrus (dramatic fluctuations in hormones) compared to females in diestrus (steady low hormones), males, and ovariectomized (OVX) females. Further, when injected into the vibrissal pad, 5HT only evoked orofacial pain behaviors in females in proestrus and estrus. As 5HT receptors are colocalized with the transient receptor potential vanilloid 1 ion channel (TRPV1), a cation channel activated by capsaicin that initiates pain signaling, it is possible that 5HT differentially potentiates TRPV1 activity leading to our observed sex differences and estrous cycle effects. We hypothesized that 5HT potentiates capsaicin‐evoked orofacial nocifensive behaviors to a greater degree when hormones are in flux. Rats were acclimated and 24 hours later received a 50 μl injection of 1.5 μg 5HT + 1 μg capsaicin, 3 μg 5HT + capsaicin, or capsaicin only into the vibrissal pad (n=6–9 per group) and orofacial nocifensive behaviors were scored as number of forelimb swipes at the injection site in 6 min bouts over 30 min. We report that rats in proestrus exhibited significant nocifensive behaviors following injection of both the lower and higher doses of 5HT with capsaicin compared to capsaicin alone. Females in estrus and males exhibited significant nocifensive behaviors only following the higher 5HT dose with capsaicin. No significant effect of 5HT on capsaicin‐evoked pain behavior was observed in OVX females or females in diestrus. We also tested whether there were differences in 5HT content in the interstitial fluid of rodent vibrissal pads following 24 hours of inflammation. Rats received a left vibrissal pad injection of 50 μl complete Freund's adjuvant (CFA) and a right vibrissal pad injection of saline. After 24 hours, punch biopsies were collected and centrifuged to obtain interstitial fluid and 5HT content was quantified by ELISA. Males had significantly less serotonin content than cycling females in the saline‐injected vibrissal pads. When CFA elevated the 5HT content, a sex difference was no longer detected. Together our data indicate that serotonin may be enhancing TRPV1 activity at subthreshold doses when estrogen is high. Estrogen exacerbation of serotonergic pain in trigeminal sensory neurons combined with greater basal levels of serotonin in orofacial tissues may be one contributing factor to the greater prevalence of trigeminal disorders in women.Support or Funding InformationThis research is supported by NIH NIDCR R15DE025970 awarded to DLA. This study was also, in part, supported by TWU Research Enhancement Grants and a Chancellor's Research Fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Does professional background influence in temporomandibular joint tissues evaluation by magnetic resonance imaging?

Context: Imaging examinations afford more consistent details than clinical evaluation in the investigation process and make the differential diagnosis of temporomandibular joint (TMJ) disorders (TMDs) easier. Aims: This study aimed to check agreement among professionals from different fields of work evaluating TMDs using magnetic resonance imaging (MRI) and based on ten diagnoses criteria: Position, shape and recapture of joint disk, joint mobility, degenerative changes, bone changes, condyle position, effusion, intramedullary edema, and avascular necrosis. Methods: An oral and maxillofacial radiologist, a medical radiologist, and a dental surgeon specialized in TMD and orofacial pain interpreted 152 MRI taken from 76 patients. A scenario simulating daily activities was devised, which neither calibration nor discussion of criteria was assessed. Interobserver agreement was measured using the Kappa coefficient. Results: Poor agreement was observed in avascular necrosis; a slight agreement was recorded in form and position of the joint disk, condyle position, effusion; fair agreement in TMJ mobility and disk recapture; moderate to almost perfect agreement in condylar changes, degenerative changes, and intramedullary edema. Conclusion: Professionals from different areas that interpret TMJ disorders using MRI did not agree on the diagnoses, especially for the soft-tissue changes.

A Self-Reported Association between Temporomandibular Joint Disorders, Headaches, and Stress.

Aims and Objectives:Temporomandibular joint disorder (TMD) is an umbrella term for a number of conditions in the area of the joint, temple, and masticatory system. Many of those with TMD also suffer from headaches and anxiety. The aims and objectives of this study were to determine if there exists an association between the Diagnostic Criteria of TMD (DC/TMD) symptom questionnaire and report of headaches as well as stress.Materials and Methods:A cross-sectional study was implemented via the use of the DC/TMD symptom questionnaire and the perceived stress scale (PSS). This was distributed conveniently among dental students in a multi-dental school setting in Riyadh, Saudi Arabia, and was completed by 152 dental students. Odds ratios, Chi-square, and their corresponding 95% confidence intervals are reported. Statistical significance was set at P ≤ 0.05.Results:Those who ticked yes for pain on the TMD pain screener for pain with chewing hard or tough food, pain on mouth opening and lateral excursion, and pain with jaw habits as parafunction were at an odds risk from twice to thrice as likely to experience headaches. Similarly, those with poor coping skills on the PSS were more likely to have headaches (P = 0.002). Likewise, positive answers on the screener and symptom questionnaire were relevant with higher stress scores on the PSS.Conclusion:This study clarifies and reiterates the intertwined power of both stress and headaches; the former being a role player in TMD progression and the latter its product. TMD is unfortunately on the rise; it should not be brushed off as a nuisance. A multidisciplinary approach in diagnosis and treatment of both TMD and headaches by a team of orofacial pain specialist, neurologist, psychiatrist and/or psychologist, and physical therapists to untangle the deceiving presentation of both conditions would not only provide a more favorable prognosis but also improve cost and time expenditures.

Effectiveness of vitamin b complex in reducing chronic temporomandibular joint disorder pain — double blind randomised clinical trial

Background: Chronic temporomandibular joint disorder (TMD) pain management has always been challenging and usually requires long-term analgesics. Commonly used analgesics have a potential for adverse effects in long-term usage, thus there is a need to look for a safer alternative analgesic option. Objectives: To evaluate efficacy of vitamin B complex (VBC) [B1, B6, B12] in reducing chronic TMD pain. Methods: 26 patients with chronic TMD pain secondary to arthralgia, osteoarthritis and disc displacement were included. The patients were allocated randomly into two groups and received either VBC tablet (B1: 242.5 mg, B6: 250 mg, B12: 1 mg) or placebo once per day for six weeks. Clinical measurements were recorded at week 0 and week 2, week 4, and week 6 to evaluate the efficacy of the treatment. Pain intensity was measured by visual analogue score (VAS) and mandibular range of movement was measured by maximal comfortable mandibular opening and lateral excursion. Adverse effects and compliance rate towards treatment were also assessed. Findings: In this 6-week clinical trial, both groups showed significant VAS pain reduction (VBC 2.49 ± 1.71; placebo 1.41 ± 1.53; P < 0.05). The amount of VAS pain reduction in the VBC group was significantly higher than in the Placebo group at week 2 (1.19 ± 1.28 versus 0.23 ± 0.90) and week 4 (2.32 ± 1.42 versus 1.25 ± 0.75; P < 0.05). No statistically significant difference was noted in mouth opening improvement. Both VBC and placebo medications were well tolerated with minimal adverse effects. Conclusion: In this study a dose of VBC (B1: 242.5 mg, B6: 250 mg, B12: 1 mg) was significantly better than placebo in reducing chronic TMD pain at week two and week four.

Effects of High-Dose Capsaicin on TMD Subjects: A Randomized Clinical Study.

Temporomandibular joint disorder (TMD) is a complex musculoskeletal disorder that presents with pain, limited jaw opening, and abnormal noises in the temporomandibular joint. Despite the significant impact that TMD has in terms of suffering and financial burden, relatively few new treatments have emerged; therefore, development of novel treatments to treat TMD pain remains a high priority. The rationale of this study was to use a double-blind, vehicle-controlled clinical trial to evaluate the effects of a high-concentration (8%) capsaicin cream on TMD. This is based on the hypothesis that targeting TRP vanilloid subfamily member 1 (TRPV1) for pain control may provide a novel method for pain relief in TMD patients. TRPV1 is primarily expressed on a population of nociceptive-specific neurons and provides a candidate target for the development of pain treatments. Capsaicin is the primary agonist for TRPV1 and has been used previously in relatively low doses (0.025% to 0.075%) as a therapeutic for a variety of pain disorders, including postherpetic neuralgia and osteoarthritis; however, analgesic efficacy remains equivocal. TMD and healthy control subjects were assigned to either an active capsaicin or vehicle control group. The treatments were applied for 2 h and then removed. Quantitative sensory testing (QST) was completed prior to drug application (baseline), 2 h after drug application, and 1 wk later. Perceived pain intensity was measured using a visual analog scale (VAS) following capsaicin or vehicle cream application. Significantly lower pain was reported in the week after application in the capsaicin-treated TMD subjects. For QST measures, there was a decreased thermal pain threshold 2 h after capsaicin application for both the control and TMD groups, but this resolved within a week. Capsaicin had no effect on pressure pain threshold or mechanical sensitivity in both TMD and healthy individuals. This study demonstrates that 8% topical capsaicin therapy is a relatively safe, simple, and effective treatment for patients with TMD. Knowledge Transfer Statement: This study evaluated a novel topical capsaicin therapy for reducing orofacial pain. The results of this study can be used to provide another treatment option for patients with TMD.

Pain detection by clinical questionnaire in patients referred for temporomandibular disorders in a Chilean hospital.

Aim: To determine pain frequency by means of a clinical screening questionnaire in patients with temporomandibular disorders (TMD) referred to the general Hospital of Valdivia (HBV) between September and December 2014. Material and method: A descriptive study, which included patients referred to the TMD Unit of the dental service at HBV between September and December 2014, was carried out. A clinical screening questionnaire was applied by an examiner in order to detect painful Temporomandibular Joint Disorders. The variables age, sex, wait time, and presence of related TMD pain were measured. Results: 101 patients were surveyed; 88.17% (84 patients) were women. Average age was 33.5 (11-70) years; 66% of patients had mandibular pain or stiffness upon awakening; 80% informed pain related to painful TMD. Conclusion: Most surveyed patients were women. Pain was highly frequent in the surveyed population; its main location was in temporal areas.