Temporomandibular Joint Inflammation Research Articles

Practice Management and Injury Prevention in Trumpet Players

This interview explores the intricate relationship between trumpet playing, practice management, and preventing injuries in performers. The discussion delves into the development of neuro-motor automatisms during practice, emphasizing their impact on biomechanisms and the potential for injuries. The most common injuries in trumpet players, including skin lesions and temporomandibular joint inflammation, and the role of excessive mouthpiece pressure are examined. The importance of efficient habits, teacher guidance, and a holistic mental and physical health approach in trumpet playing is highlighted. Additionally, the interview sheds light on the significance of understanding the unity of body and mind for optimal performance.

N-methyl-D-aspartate Receptor Subunits 2A and 2B Mediate Connexins and Pannexins in the Trigeminal Ganglion Involved in Orofacial Inflammatory Allodynia during Temporomandibular Joint Inflammation.

Temporomandibular joint osteoarthritis (TMJOA) is a severe form of temporomandibular joint disorders (TMD), and orofacial inflammatory allodynia is one of its common symptoms which lacks effective treatment. N-methyl-D-aspartate receptor (NMDAR), particularly its subtypes GluN2A and GluN2B, along with gap junctions (GJs), are key players in the mediation of inflammatory pain. However, the precise regulatory mechanisms of GluN2A, GluN2B, and GJs in orofacial inflammatory allodynia during TMJ inflammation still remain unclear. Here, we established the TMJ inflammation model by injecting Complete Freund's adjuvant (CFA) into the TMJ and used Cre/loxp site-specific recombination system to conditionally knock out (CKO) GluN2A and GluN2B in the trigeminal ganglion (TG). Von-frey test results indicated that CFA-induced mechanical allodynia in the TMJ region was relieved in GluN2A and GluN2B deficient mice. In vivo, CFA significantly up-regulated the expression of GluN2A and GluN2B, Gjb1, Gjb2, Gjc2 and Panx3 in the TG, and GluN2A and GluN2B CKO played different roles in mediating the expression of Gjb1, Gjb2, Gjc2 and Panx3. In vitro, NMDA up-regulated the expression of Gjb1, Gjb2, Gjc2 and Panx3 in satellite glial cells (SGCs) as well as promoted the intercellular communication between SGCs, and GluN2A and GluN2B knocking down (KD) altered the expression and function differently. NMDAR regulated Gjb1 and Panx3 through ERK1/2 pathway, and mediated Gjb2 and Gjc2 through MAPK, PKA, and PKC intracellular signaling pathways. These findings shed light on the distinct functions of GluN2A and GluN2B in mediating peripheral sensitization induced by TMJ inflammation in the TG, offering potential therapeutic targets for managing orofacial inflammatory allodynia.

Enkephalin Rescues Temporomandibular Joint Pain-Related Behavior in Rats.

Temporomandibular joint disorders include a variety of clinical syndromes that are difficult to manage if associated with debilitating severe jaw pain. Thus, seeking additional experimental therapies for temporomandibular joint pain reduction is warranted. Targeted enkephalin gene therapy approaches provide clear promise for pain control. The studies detailed here indicate significant analgesia and protection of joint tissue are provided after injection of an overexpression viral vector gene therapy near the joint. The viral vector gene therapy described provides overexpression of naturally occurring opioid peptides after its uptake by trigeminal nerve endings. The viral vectors act as independent "minipump" sources for the opioid peptide synthesis in the neuronal cytoplasm producing the intended biological function, reduction of pain, and tissue repair. The antinociceptive effects provided with this delivery method of opioid expression persist for over 4weeks. This is coincident with the expected time frame for the duration of the transgene overproduction of the endogenous opioid peptide before its diminution due to dormancy of the virus. These experimental studies establish a basis for the use of replication-defective herpes simplex type 1-based gene therapy for severe chronic inflammatory temporomandibular joint destruction and pain. As innovative means of significantly reducing joint inflammation and preserving tissue architecture, gene therapies may extend their clinical usefulness for patients with temporomandibular joint disorders.

An analysis of the relationship between dietary pattern changes and temporomandibular joint inflammation in diabetic rats.

The temporomandibular joint (TMJ) is the most commonly used joint in the human body. Recent studies have shown pathologic relationships between inflammation, diabetes, and musculoskeletal disorders (MSDs). Chewing disorder is a significant sign of dysfunction in the masticatory system. This study investigated dietary pattern changes in response to TMJ inflammation in diabetic rats. This experimental study was carried out on 30 male rats. The rats were fed concentrated 20-mg dietary tablets. Complete Freund's adjuvant (CFA) was used to induce TMJ inflammation and streptozotocin (STZ) was used to induce diabetes. The animals were randomly divided into three groups (n=10), including group I (CFA+STZ), group II (healthy rats+CFA), and group III (healthy rats, no injection). Parameters such as overall food intake, food intake duration, food intake frequency, and the interval between meals were recorded in a checklist and analyzed by Mann-Whitney and Kruskal-Wallis tests (P<0.05). The results showed no significant difference between groups in overall food intake and food intake frequency on days 0 and 1, but this difference was significant from day 2 to day 7. Regarding the time and end of food intake, there was a significant difference between the three groups from day 1 to day 7, but this difference was not significant on day zero. Dietary pattern changes were similar in the diabetic TMJ inflammation and TMJ inflammation groups. These changes can be used as a behavioral marker for TMJ inflammation in rats.

TET1-mediated epigenetic regulation of tumor necrosis factor-α in trigeminal ganglia contributes to chronic temporomandibular joint pain

Chronic temporomandibular joint (TMJ) pain profoundly affects patients' quality of life. Trigeminal tumor necrosis factor-α (TNFα) plays a pivotal role in mediating TMJ pain in mice, yet the underlying epigenetic mechanisms remain enigmatic. To unravel these epigenetic intricacies, we employed a multifaceted approach. Hydroxymethylated DNA immunoprecipitation (hMeDIP) and chromatin immunoprecipitation (ChIP) followed by qPCR were employed to investigate the demethylation of TNFα gene (Tnfa) and its regulation by ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in a chronic TMJ pain mouse model. The global levels of 5-hydroxymethylcytosine (5hmc) and percentage of 5hmc at the Tnfa promoter region were measured in the trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) following complete Freund's adjuvant (CFA) or saline treatment. TET1 knockdown and pain behavioral testing were conducted to ascertain the role of TET1-mediated epigenetic regulation of TNFα in the pathogenesis of chronic TMJ pain. Our finding revealed an increase in 5hmc at the Tnfa promoter region in both TG and Sp5C of CFA-treated mice. TET1 was upregulated in the mouse TG, and the ChIP result showed TET1 direct binding to the Tnfa promoter, with higher efficiency in the CFA-treated group. Immunofluorescence revealed the predominant expression of TET1 in trigeminal neurons. TET1 knockdown in the TG significantly reversed CFA-induced TNFα upregulation and alleviated chronic TMJ pain. In conclusion, our study implicates TET1 as a vital epigenetic regulator contributing to chronic inflammatory TMJ pain via trigeminal TNFα signaling. Targeting TET1 holds promise for epigenetic interventions in TMJ pain management.

Morphostructural changes in the brain of experimental animals after using mesenchymal stem cells in the temporomandibular joint inflammation model

The article presents the results of structural and functional transformations in cerebellum, trigeminal nuclei, and hippocampus of male Wistar rats against the background of injection of mesenchymal stem cells (MSCs) into Meckel’s space in the temporomandibular joint (TMJ) inflammation model.The aim of the study was to clarify the effect of MSCs injections into Meckel’s space on the morphostructural features of cerebellum, trigeminal nuclei, and hippocampus in the TMJ inflammation model.Injecting the mesenchymal stem cells into Meckel’s space in an inflammatory model of the right lower temporomandibular joint promotes the structure restoration of the ganglionic layer of the cerebellum, the spinal nuclei of the trigeminal nerve, and the hippocampus of rats by the 28th day. This is manifested in increasing the neuronal density, decreasing the neurodegeneration index, and in activating glia elements.

Umbilical Cord Stem Cell Lysate: A New Biologic Injectate for the Putative Treatment of Acute Temporomandibular Joint Inflammation.

To compare in vivo, the acute anti-inflammatory effects of a lysate derived from human umbilical perivascular mesenchymal cells with the cells themselves in both an established hind-paw model of carrageenan-induced inflammation and also in the inflamed temporomandibular joint. Human umbilical cord perivascular cells were harvested and cultured in xeno- and serum-free conditions to P3. In addition, P3 cells were used to prepare a proprietary 0.22 micron filtered lysate. First, CD1 immunocompetent mice underwent unilateral hind-paw injections of carrageenan for induction of inflammation, followed immediately by treatment with saline (negative control), 1% cell lysate, or viable cells. The contralateral paw remained un-injected with carrageenan. Paw circumference was measured prior to injections and 48 hr later and myeloperoxidase and TNF-alpha concentrations were measured post-sacrifice in excised tissue. Second, immunocompetent Male Wistar rats underwent unilateral intra-articular temporomandibular (TMJ) injections from the same treatment groups and were sacrificed at 4 and 48 hr post-injection. The contralateral TMJ remained un-injected with carrageenan. Articular tissue and synovial aspirates, from the treated TMJ were obtained for histologic and leukocyte infiltration analyses. The lysate and cell-treated hind-paw demonstrated reduced tissue edema, and significantly lower concentrations of myeloperoxidase and TNF-alpha at 48 hr compared to untreated controls. Treated TMJs demonstrated lower concentrations of leukocytes in the synovium compared to controls and histologic evidence, in the peri-articular tissue, of reduced inflammation. In this preliminary study, both the human umbilical perivascular cells and a highly diluted lysate produced therefrom were anti-inflammatory.

IL-38 suppresses macrophage M1 polarization to ameliorate synovial inflammation in the TMJ via GLUT-1 inhibition

ObjectivesInterleukin (IL)-38 was discovered as an anti-inflammatory factor. However, IL-38′s role in M1 macrophage polarization in the temporomandibular joint (TMJ) and the related mechanism are still unclear. We aimed to explore the effect and the mechanism of IL-38 on synovial inflammation in the TMJ in this study. MethodsThe expression of IL-38 in the TMJ synovium and macrophages was determined using immunohistochemistry (IHC) and Western blotting (WB). M1 macrophage polarization was induced by LPS, the macrophages were pre-treated with IL-38, and the levels of inflammatory markers associated with M1 macrophages were measured. To assess the mechanism of IL-38, small-interfering RNA (siRNA)‐GLUT-1 and STF31 were administered to macrophages, and the affected pathways were identified by WB. The effect of macrophage-conditioned medium (CM) on chondrocyte function was also determined. Finally, a mouse model of CFA‐induced TMJ inflammation was established. Histological staining and IHC were used to determine the effect of IL-38. ResultsIL-38 was detected at high levels in macrophages after lipopolysaccharide (LPS)challenge, and IL-38 downregulated M1 macrophage-related proinflammatory markers (iNOS, IL-6, TNF-α, and COX-2) in vitro. IL-38 suppressed M1 polarization by inhibiting GLUT-1 expression, NF-κB signaling, and MAPK signaling. Intriguingly, CM from macrophages that were pretreated with IL-38 and STF31 decreased inflammatory protein expression in chondrocytes. In addition, intra-articular injection of recombinant IL-38 ameliorated synovial inflammation in the TMJ by inhibiting M1 macrophage polarization and suppressing cartilage inflammation in vivo. ConclusionsIL-38 is a novel anti-inflammatory factor that contributes to alleviating TMJ inflammation by inhibiting macrophage M1 polarization, thereby ameliorating chondrocyte inflammation and restoring TMJ homeostasis.

Therapeutic and Side Effects of Intra-articular and Intraperitoneal Injections of Corticosteroids on Temporomandibular Joint Inflammation: A Review Study

Background and Objectives This study aims to investigate the therapeutic effects and side effects of intraarticular (IA) and intra-peritoneal (IP) injections of corticosteroids on temporomandibular joint (TMJ) inflammation Subjects and Methods This is a review study that was conducted on related studies published from 1990 to 2022 which were searched in Web of Science, PubMed, Scopus, Google Scholar, SID, Magiran and IranMedex using the keywords “temporomandibular joint”, “intra-articular injection”, “corticosteroid”, “adverse effects”, “juvenile arthritis”, “osteoarthritis”, “ Juvenile idiopathic arthritis”,”degenerative joint disorders”, and “temporomandibular joint disorders”. Results A total of 13 studies met the inclusion criteria. Two studies were related to IP injection, 8 related to IA injection, two studies compared the effect of IA and IP drug injection, and one study investigated the TMJ arthrocentesis and IP drug injection. In 4 studies, the aim was to compare the effectivness of corticosteroids and hyaluronic acid in improving temporomandibular disorders. Nine studies found that the use of corticosteroids is beneficial for the treatment of TMJ inflammation, and 7 studies reported complications such as condylar resorption. Conclusion Since the use of corticosteroids in treatment of TMJ disorders is not without complications, there is a need to conduct extensive studies on various drugs with anti-inflammatory effects and lowest side effects to replace them with corticosteroids.

Silencing of TRPV4-expressing sensory neurons attenuates temporomandibular disorders pain.

Identification of potential therapeutic targets is needed for temporomandibular disorders (TMD) pain, the most common form of orofacial pain, because current treatments lack efficacy. Considering TMD pain is critically mediated by the trigeminal ganglion (TG) sensory neurons, functional blockade of nociceptive neurons in the TG may provide an effective approach for mitigating pain associated with TMD. We have previously shown that TRPV4, a polymodally-activated ion channel, is expressed in TG nociceptive neurons. Yet, it remains unexplored whether functional silencing of TRPV4-expressing TG neurons attenuates TMD pain. In this study, we demonstrated that co-application of a positively charged, membrane-impermeable lidocaine derivative QX-314 with the TRPV4 selective agonist GSK101 suppressed the excitability of TG neurons. Moreover, co-administration of QX-314 and GSK101 into the TG significantly attenuated pain in mouse models of temporomandibular joint (TMJ) inflammation and masseter muscle injury. Collectively, these results suggest TRPV4-expressing TG neurons represent a potential target for TMD pain.

The effect of acute equine temporomandibular joint inflammation on response to rein-tension and kinematics.

Although the temporomandibular joint (TMJ) is the major contact point between the reins in the riders' hand, the bit in the mouth, and the rest of the horse under saddle, the role of inflammation of this joint on equine locomotion and rein tension is unknown. To determine the effect of acute TMJ inflammation on rein-tension and horse movement when horses were long-reined on a treadmill. A randomized, controlled, cross-over design. Five horses were trained by one clinician to walk and trot on a treadmill wearing long-reining equipment instrumented with a rein-tension device and reflective optical tracking markers. Subjective assessment of horse's dominant side, and movement, were determined without rein-tension (free walk and trot); and with rein-tension (long-reined walk and trot). Continuous rein-force data from both sides were collected over ~60s from each trial. Movement was recorded using a 12-camera optical motion capture system. One randomly assigned TMJ was subsequently injected with lipopolysaccharide and the treadmill tests repeated by investigators blinded to treatment side. A second, identical assessment was performed 10 days later with the opposite TMJ being the target of intervention. All horses showed reduced rein-tension on the injected (inflamed) side. Increased rein-tension was required on the non-injected side at trot, to maintain them in the correct position on the treadmill post-injection. The only kinematic variable to show any significant change due to rein tension or TMJ inflammation during the walk or trot was an increase in forward head tilt in the presence of rein tension in the trot after injection. Low number of horses and investigation of response to acute inflammation only. TMJ inflammation changed, subjectively and objectively, the response to rein-input, but the horses did not become lame.

Influence of TRPV1 on Thermal Nociception in Rats with Temporomandibular Joint Persistent Inflammation Evaluated by the Operant Orofacial Pain Assessment Device (OPAD).

Temporomandibular joint (TMJ)-associated inflammation contributes to the pain reported by patients with temporomandibular disorders (TMD). It is common for patients diagnosed with TMD to report pain in the masticatory muscles and temporomandibular joints, headache, and jaw movement disturbances. Although TMD can have different origins, including trauma and malocclusion disorder, anxiety/depression substantially impacts the development and maintenance of TMD. In general, rodent studies on orofacial pain mechanisms involve the use of tests originally developed for other body regions, which were adapted to the orofacial area. To overcome limitations and expand knowledge in orofacial pain, our group validated and characterized an operant assessment paradigm in rats with both hot and cold stimuli as well mechanical stimuli. Nevertheless, persistent inflammation of the TMJ has not been evaluated with this operant orofacial pain assessment device (OPAD). We characterized the thermal orofacial sensitivity for cold, neutral, and hot stimuli during the development of TMD using the OPAD behavior test. In addition, we evaluated the role of transient receptor potential vanilloid 1 (TRPV1) expressing nociceptors in rats with persistent TMJ inflammation. The experiments were performed in male and female rats with TMJ inflammation induced by carrageenan (CARR). Additionally, resiniferatoxin (RTX) was administered into the TMJs prior CARR to lesion TRPV1-expressing neurons to evaluate the role of TRPV1-expressing neurons. We evidenced an increase in the number of facial contacts and changes in the number of reward licks per stimulus on neutral (37°C) and cold (21°C) temperatures. However, at the hot temperature (42°C), the inflammation did not induce changes in the OPAD test. The prior administration of RTX in the TMJ prevented the allodynia and thermal hyperalgesia induced by CARR. We showed that TRPV-expressing neurons are involved in the sensitivity to carrageenan-induced pain in male and female rats evaluated in the OPAD.

Effect of sound-induced repeated stress on the development of pain and inflammation in the temporomandibular joint of female and male rats.

Temporomandibular disorder (TMD) is a common painful condition of the temporomandibular joint (TMJ) and associated structures. Stress is a significant risk factor for developing this painful condition that predominantly affects women. This study aimed to test the hypothesis that stress increases the risk of developing TMJ pain by facilitating inflammatory mechanisms in female and male rats. To test this hypothesis, we evaluated TMJ carrageenan-induced expression of pro-inflammatory cytokines and migration of inflammatory cells and TMJ formalin-induced nociception in female and male rats submitted to a repeated stress protocol induced by sound. We found that sound-induced repeated stress facilitates TMJ inflammation and contributes to TMJ nociception development equally in females and males. We conclude that stress is a risk factor for developing painful TMJ conditions in males and females, at least in part, by favoring the inflammatory process similarly in both sexes.

TMEM100, a regulator of TRPV1-TRPA1 interaction, contributes to temporomandibular disorder pain.

There is an unmet need to identify new therapeutic targets for temporomandibular disorder (TMD) pain because current treatments are limited and unsatisfactory. TMEM100, a two-transmembrane protein, was recently identified as a regulator to weaken the TRPA1-TRPV1 physical association, resulting in disinhibition of TRPA1 activity in sensory neurons. Recent studies have also shown that Tmem100, Trpa1, and Trpv1 mRNAs were upregulated in trigeminal ganglion (TG) after inflammation of the temporomandibular joint (TMJ) associated tissues. These findings raise a critical question regarding whether TMEM100 in TG neurons is involved in TMD pain via regulating the TRPA1-TRPV1 functional interaction. Here, using two mouse models of TMD pain induced by TMJ inflammation or masseter muscle injury, we found that global knockout or systemic inhibition of TRPA1 and TRPV1 attenuated pain. In line with their increased genes, mice exhibited significant upregulation of TMEM100, TRPA1, and TRPV1 at the protein levels in TG neurons after TMD pain. Importantly, TMEM100 co-expressed with TRPA1 and TRPV1 in TG neurons-innervating the TMJ and masseter muscle and their co-expression was increased after TMD pain. Moreover, the enhanced activity of TRPA1 in TG neurons evoked by TMJ inflammation or masseter muscle injury was suppressed by inhibition of TMEM100. Selective deletion of Tmem100 in TG neurons or local administration of TMEM100 inhibitor into the TMJ or masseter muscle attenuated TMD pain. Together, these results suggest that TMEM100 in TG neurons contributes to TMD pain by regulating TRPA1 activity within the TRPA1-TRPV1 complex. TMEM100 therefore represents a potential novel target-of-interest for TMD pain.

Therapeutic effect of alendronate in an experimental temporomandibular joint osteoarthritis.

Temporomandibular joint osteoarthritis is a common degenerative joint disease. This disease negatively affects the daily life, speech and chewing functions of patients. This study aimed to evaluate the effects of intra-articular injection of alendronate to osteoarthritis, which has a protective effect on bone and cartilage tissue and helps reduce inflammation in temporomandibular joint osteoarthritis. A total of 24 Wistar albino rats were used in the study. Rats were divided into four groups: study, saline, control and sham. In both saline and control groups, monosodium iodoacetate was injected intra-articularly to induce osteoarthritis. Alendronate was administered intra-articularly to the study group weekly for 4 weeks. In the saline group, saline was administered by intra-articular injection. At the end of the 12th week, all groups were sacrificed. Mandibular condyle tissues were examined histopathologically. According to the results, osteoarthritic changes in the control group were higher than those in the study group (p < .05). No significant reduction in osteoarthritic changes was observed in the saline group (p > .05). Significant osteoarthritis findings were observed in all groups compared with the sham group (p < .05). Intra-articular injection of alendronate was found to have positive results on TMJ osteoarthritis. In addition, it was seen that alendronate has effects on reducing cartilage tissue degeneration and loss of matrix proteins.

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.

Transcriptomic Analysis of Trigeminal Ganglion and Spinal Trigeminal Nucleus Caudalis in Mice with Inflammatory Temporomandibular Joint Pain

BackgroundPersistent facial pain heavily impacts the quality of life in patients with temporomandibular joint (TMJ) disorders. Previous studies have demonstrated that long non-coding ribonucleic acid (lncRNA) is an important regulator of pain. In this study, we aimed to analyze lncRNA expression in the whole transcriptome of trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in a chronic inflammatory TMJ pain mouse model.MethodsChronic inflammatory TMJ pain was induced by intra-TMJ injection of complete Freund’s adjuvant (CFA). Mouse TG and Sp5C tissues were harvested on day 4 after CFA injection. The lncRNA expression patterns in the whole transcriptome of TG and Sp5C were profiled with RNA sequencing.ResultsWe observed that 38 lncRNAs and 849 mRNAs were differentially expressed after CFA treatment. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis further revealed relationships among those differentially expressed lncRNAs and mRNAs and their potential functions. Specific categories of biological process, cellular processes, and molecular function of the differentially expressed transcripts were ascertained.ConclusionOur results suggest that lncRNA expression in the whole transcriptome of trigeminal nociceptive system could contribute to the molecular mechanisms that underlie chronic inflammatory TMJ pain.

Cytokines in temporomandibular joint synovial fluid and tissue in relation to inflammation.

BackgroundSynovial tissue is known to be the origin of inflammation in joint disease. Despite this, synovial fluid is the main biological specimen of choice in temporomandibular joint (TMJ) inflammation and pathology biomarker research. No comparison of TMJ protein content between synovial fluid and synovial tissue has been made.ObjectivesThe aim of this study was to investigate whether cytokine concentrations in synovial fluid can be related to cytokine concentrations in synovial tissue and to analyse correlation of clinical parameters reflecting local inflammation to cytokine concentrations.MethodsSynovial tissue and fluid samples were obtained during the same surgical procedure from a cohort of 101 patients with TMJ disorders. Interleukin (IL) 1β, IL‐6, IL‐8, IL‐10 and tumour necrosis factor α (TNF‐α) were analysed in the samples and an intraindividual correlation made. Various patient‐specific factors related to TMJ inflammation were associated with the cytokine concentrations in synovial fluid and tissue.ResultsNo correlation between cytokine concentration in synovial fluid and synovial tissue was found, except for IL‐8 (ρ = .284, p = .024). Synovial tissue cytokines correlated strongly to inflammation‐related factors: diagnosis (IL‐1β, p = .001; TNF‐α, p = .000; IL‐10, p = .000), TMJ palpation pain (IL‐1β, p = .024; TNF‐α, p = .025), synovitis score (IL‐1β, p = .015) and subjective TMJ pain (TNF‐α, p = .016). Synovial fluid cytokines showed no significant relations to inflammation.ConclusionsThe investigated cytokine concentrations showed weak correlations between synovial fluid and synovial tissue, besides IL‐8. Synovial tissue appeared to reflect inflammation to a higher extent than synovial fluid. Thus, suggesting that synovial tissue research should complement synovial fluid in future explorations of TMJ pathology and inflammation.

C-Reactive Protein Knockout Attenuates Temporomandibular Joint Inflammation in Rats.

Background C-reactive protein (CRP), a biomarker of inflammation, is highly expressed in osteoarthritis- (OA-) related diseases, but its exact role remains unknown. In this study, we evaluated the biological effect of CRP on temporomandibular joint (TMJ) inflammation. Methods Freund's complete adjuvant (CFA) was used to induce TMJ inflammation in CRP-knockout (CRP-/-) and control rats. Degenerative changes in the TMJ were compared to elucidate the role of CRP in TMJ inflammation. In addition, inflammatory cytokines, macrophage activation, and osteoclast differentiation were evaluated by real-time quantitative polymerase chain reaction, immunohistochemistry, and tartrate-resistant phosphatase staining to explore the potential regulatory mechanism. Results Compared to the control, CFA induced TMJ inflammation, which increased systemic and local CRP expression. Furthermore, CRP-/- rats exhibited less severe inflammatory symptoms. The downregulation of proinflammatory cytokines (interleukin- (IL-) 1β and IL-6) and upregulation of the anti-inflammatory cytokine IL-10 were detected in CRP-/- rats, which also exhibited reduced macrophage activation and osteoclast differentiation. Conclusion These results indicated that controlling the highly elevated levels of CRP during inflammation could modify the cytokine profile, macrophage activation, and osteoclast differentiation, thus, providing beneficial effects for TMJ-OA prevention and treatment.

Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation.

This study investigates the role of transient receptor potential ankyrin 1 (TRPA1) in murine temporomandibular joint (TMJ) inflammatory hyperalgesia and the influence of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Two distinct murine models of TMJ pain and inflammation (zymosan and CFA) were established. Spontaneous pain-like behaviours were observed as unilateral front paw cheek wipes. Ipsilateral cheek blood flow was used as a measure of ongoing inflammation, which, to our knowledge, is a novel approach to assessing real-time inflammation in the TMJ. Joint tissue and trigeminal ganglia were collected for ex vivo investigation. Both zymosan and CFA induced a time-dependent increase in hyperalgesia and inflammation biomarkers. Zymosan induced a significant effect after 4 h, correlating with a significantly increased IL-1β protein expression. CFA (50 µg) induced a more sustained response. The TRPA1 receptor antagonist A967079 significantly inhibited hyper-nociception. The NLRP3 inhibitor MCC950 similarly inhibited hyper-nociception, also attenuating inflammatory markers. In the trigeminal ganglia, CFA-induced CGRP expression showed trends of inhibition by A967079, whilst lba1 immunofluorescence was significantly inhibited by A967079 and MCC950, where the effect of TRPA1 inhibition lasted up to 14 days. Our results show that stimulation of TRPA1 is key to the TMJ pain. However, the inflammasome inhibitor exhibited similar properties in attenuating these pain-like behaviours, in addition to some inflammatory markers. This indicates that in addition to the therapeutic targeting of TRPA1, NLRP3 inhibition may provide a novel therapeutic strategy for TMJ inflammation and pain.