Clinical diagnosis of temporomandibular joint arthritis

Evidence‐based clinical diagnostic criteria for temporomandibular joint (TMJ) arthritis are not available. To establish (i) criteria for clinical diagnosis of TMJ arthritis and (ii) clinical variables useful to determine inflammatory activity in TMJ arthritis using synovial fluid levels of inflammatory mediators as the reference standard. A calibrated examiner assessed TMJ pain, function, noise and occlusal changes in 219 TMJs (141 patients, 15 healthy individuals). TMJ synovial fluid samples were obtained with a push–pull technique using the hydroxycobalamin method and analysed for TNF, TNFsRII, IL‐1β, IL‐1ra, IL‐1sRII, IL‐6 and serotonin. If any inflammatory mediator concentration exceeded normal, the TMJ was considered as arthritic. In the patient group, 71% of the joints were arthritic. Of those, 93% were painful. About 66% of the non‐arthritic TMJs were painful to some degree. Intensity of TMJ resting pain and TMJ maximum opening pain, number of jaw movements causing TMJ pain and laterotrusive movement to the contralateral side significantly explained presence of arthritis (AUC 0.72, P < .001). Based on these findings, criteria for possible, probable and definite TMJ arthritis were determined. Arthritic TMJs with high inflammatory activity showed higher pain intensity on maximum mouth opening (P < .001) and higher number of painful mandibular movements (P = .004) than TMJs with low inflammatory activity. The combination TMJ pain on maximum mouth opening and Contralateral laterotrusion <8 mm appears to have diagnostic value for TMJ arthritis. Among arthritic TMJs, higher TMJ pain intensity on maximum mouth opening and number of mandibular movements causing TMJ pain indicates higher inflammatory activity.     

颞下颌关节关节液中5-羟色胺的表达与颞下颌关节关节源性疼痛的关系

目的探讨颞下颌关节紊乱病(TMD)患者关节液中5-羟色胺(5-HT)的表达水平与颞下颌关节(TMJ)关节源性疼痛的关系。方法用酶联免疫吸附试验法检测TMD患者的126侧关节和健康志愿者的32侧关节的关节液标本中的5-HT。126侧TMD患者的关节液标本分为疼痛组(n=90)和无痛组(n=36);32名正常志愿者的32侧关节液设为对照组(n=32)。结果所有标本都检出5-HT,无痛组含量为(178.750±64.979)ng/ml,疼痛组为(223.522±82.636)ng/ml,对照组为(136.125±55.075)ng/ml。疼痛组与无痛组、疼痛组与对照组以及无痛组与对照组间差异有显著性(P<0.05)。结论TMD患者关节内存在炎症状态,关节疼痛与关节液中5-HT的表达水平密切相关,但与疼痛程度的关系尚需进一步研究。     

Tumor necrosis factor-alpha in synovial fluid and plasma from patients with chronic connective tissue disease and its relation to temporomandibular joint pain.

PURPOSE: The purpose of this study was to determine the level of tumor necrosis factor-alpha (TNF-alpha) in the temporomandibular joint (TMJ) synovial fluid (SF-TNF-alpha) and blood plasma (P-TNF-alpha) of patients with chronic inflammatory connective tissue disease and investigate its relation to TMJ pain, hyperalgesia, and allodynia. PATIENTS AND METHODS: Twenty-four patients with a diagnosis of chronic inflammatory connective tissue disease and TMJ pain were included in the study. Visual analog scale, tenderness of the TMJ, and pain at mandibular movements were registered, and the pressure pain threshold and pressure pain tolerance levels were measured. TMJ synovial fluid samples and blood plasma were analyzed for TNF-alpha and the levels related to TMJ pain, hyperalgesia, and allodynia. RESULTS: TNF-alpha was present in the TMJ synovial fluid of 8 of 24 patients at levels significantly exceeding those in plasma at the same visit. The presence of SF-TNF-alpha showed a significant positive correlation to TMJ pain at maximum voluntary mouth opening and tenderness to posterior palpation of the TMJ. CONCLUSION: Local production of TNF-alpha occurs in the TMJ synovium of patients with chronic inflammatory connective tissue disease. Pain on mandibular movement and tenderness on posterior palpation (allodynia) of the TMJ is related to the level of SF-TNF-alpha.     

Spontaneous temporomandibular joint arthropathy in MRL-lpr/lpr mice

The temporomandibular joint (TMJ) in spontaneously arthritic MRL lpr/lpr (MRL/1) mice has been histologically analysed. After decalcification and standardized preparation of the joint tissue, histological sections were examined for presence of synovial hypertrophy, synovial villi, pannus tissue, erosions, cysts and signs of periarticular inflammation. In 12 of 13 TMJs examined, histopathological changes indicating a state of arthropathy were found. The most prevalent finding was synovial proliferation, which was frequently detected at the insertion of the synovial membrane to the bone. Two or more signs of inflammatory involvement including synovial proliferation, pannus tissue and bone erosion were seen in 5 mice with a predominance among the oldest mice (>5 months of age). No lymphocytic cell infiltration was found in the analyzed synovial tissues of the TMJ. In contrast, lymphocytes were observed in the vicinity of periarticular blood vessels and tendons. It is concluded that the TMJ is frequently involved in the arthritic disease of autoimmune MRL/1 mice.     

Interleukin-1beta in antigen-induced arthritis of the rabbit temporomandibular joint

The aim was to investigate joint perfusate levels of interleukin-1beta (IL-1beta) in antigen-induced monoarthritis of the rabbit temporomandibular (TMJ) and knee joints. Twenty-four adult male New Zealand White rabbits were divided into three groups: a control group as well as TMJ arthritis and knee joint arthritis groups. After sensitization, unilateral arthritis was induced by intra-articular injection with ovalbumin and the contralateral joint was injected with saline 3 weeks after induction of arthritis. Joints were then perfused continuously with saline and samples were collected at 10-min intervals over a 50-min period. The IL-1beta concentrations in the samples were then analyzed. After killing the animals, the joints were examined histologically. The IL-1beta concentrations in the samples from the arthritic TMJs and knee joints were significantly higher than in the saline-injected and the control joints. Histological signs of chronic arthritis of similar severity were found in both joints. The IL-1beta levels in the samples from the arthritic TM and knee joints correlated with the histological severity of the arthritis, including pannus formation. In conclusion, this study shows that IL-1beta is released in the synovium of rabbit TMJs and knee joints during antigen-induced arthritis, and that high IL-1beta levels in synovial fluid are associated with histological signs of inflammation including, pannus tissue formation.     

Spontaneous temporomandibular joint arthropathy in MRL-lpr/lpr mice

The temporomandibular joint (TMJ) in spontaneously arthritic MRL lpr/lpr (MRL/l) mice has been histologically analysed. After decalcification and standardized preparation of the joint tissue, histological sections were examined for presence of synovial hypertrophy, synovial villi, pannus tissue, erosions, cysts and signs of periarticular inflammation. In 12 of 13 TMJs examined, histopathological changes indicating a state of arthropathy were found. The most prevalent finding was synovial proliferation, which was frequently detected at the insertion of the synovial membrane to the bone. Two or more signs of inflammatory involvement including synovial proliferation, pannus tissue and bone erosion were seen in 5 mice with a predominance among the oldest mice (greater than or equal to 5 months of age). No lymphocytic cell infiltration was found in the analyzed synovial tissues of the TMJ. In contrast, lymphocytes were observed in the vicinity of periarticular blood vessels and tendons. It is concluded that the TMJ is frequently involved in the arthritic disease of autoimmune MRL/l mice.     

Effects of capsaicin in temporomandibular joint arthritis in rats

Temporomandibular joint (TMJ) arthritis was induced in female Lewis rats by unilateral injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil into the TMJ. Control rats received paraffin oil by the same route. Arthritic and control rats were pretreated either with capsaicin or denervation of the mandibular branch of the trigeminal nerve. Tissues were collected for neuropeptide extraction and analysed by radioimmunoassay and reverse-phase high-performance liquid chromatography. In all groups, the levels of substance P- (SP), calcitonin gene-related peptide- (CGRP) and neuropeptide Y- (NPY) like immunoreactivity (LI) were higher in the trigeminal ganglia than in the TMJs. In control rats, capsaicin significantly lowered the levels of SP-LI in the trigeminal ganglia and TMJ, but not CGRP-LI and NPY-LI. In the arthritic rats, capsaicin pretreatment significantly lowered the SP-LI and CGRP-LI in the trigeminal ganglia and TMJ, but not the NPY-LI. In the trigeminal ganglia the unilateral denervation significantly lowered SP-LI in control rats, and in arthritic rats SP-LI and CGRP-LI. On the denervated side of the arthritic TMJ, NPY-LI, SP-LI and CGRP- LI were significantly lowered as compared to the arthritic control rats and to the contralateral side. In this rat model, pretreatment with capsaicin and surgical denervation decreased the neuropeptide content in the trigeminal ganglia and the TMJ. The results clearly demonstrate a close interaction between increased neuropeptide release from sensory and sympathetic neurones after induction of arthritis in the rat.     

Temporomandibular joint pressure pain threshold is systemically modulated in rheumatoid arthritis

AIMS: To investigate the relative importance of systemic and local inflammatory mediators (serotonin: 5-HT; tumor necrosis factor: TNF; soluble interleukin-1 receptor II: IL-1sRII) in the modulation of temporomandibular joint (TMJ) pressure pain threshold in patients with seropositive or seronegative rheumatoid arthritis (RA) and to investigate to what extent TMJ pressure pain threshold is related to other TMJ pain parameters. METHODS: Sixty patients with seropositive RA for rheumatoid factor and 74 patients with seronegative RA involving the TMJ were investigated regarding synovial fluid and plasma levels of IL-1sRII, 5-HT, and TNF as well as erythrocyte sedimentation rate, C-reactive protein, thrombocyte particle count, and rheumatoid factor in blood. TMJ resting pain, movement pain, tenderness, and palpebral pain reflex to digital palpation and TMJ pressure pain threshold were examined. RESULTS: Statistical analyses indicated that TMJ pressure pain threshold was only correlated to systemic factors. TMJ movement pain was in turn mainly correlated to systemic mediators in the seropositive patients but to local mediators in the seronegative patients where synovial fluid IL-1sRII was positively correlated to TMJ pain on mouth opening. Seropositive patients had higher systemic inflammatory activity but lower TMJ movement pain intensities than seronegative patients. CONCLUSION: The results indicate that TMJ pressure pain threshold is modulated by systemic rather than local inflammatory mediators and suggest that it is unrelated or only weakly related to other TMJ pain entities in RA patients. A rheumatoid factor-dependent systemic modulation, in combination with local factors, seems to account for TMJ pain in RA patients.     

Synovectomy and diskectomy of the temporomandibular joint in patients with chronic arthritic disease compared with diskectomies in patients with internal derangement. A 3-year follow-up study

Twenty-five temporomandibular joints (TMJs) in 15 patients with chronic arthritic disease were treated with synovectomy and diskectomy. Twenty patients with internal derangement of 27 TMJs treated with diskectomy served as a control group. A response in pain relief was seen in 73% of the patients with chronic arthritic disease and in 80% of the patients with internal derangement 3 yr postoperatively. In both groups of patients a significant increase in mouth opening capacity and lateral movement of the mandible was seen postoperatively, with no significant difference in the improvement between the two groups. Four patients with chronic arthritic disease were reoperated within the 3-yr observation period. This study indicates that synovectomy and diskectomy of the TMJ may reduce pain and improve mandibular function in patients with severe chronic arthritic TMJ disease.     

Interleukin-1beta, interleukin-1 receptor antagonist, and interleukin-1 soluble receptor II in temporomandibular joint synovial fluid from patients with chronic polyarthritides.

PURPOSE: The aim of this study was to investigate whether interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra), or soluble IL-1 receptor II (sIL-1RII) in synovial fluid or plasma is associated with joint pain or signs of tissue destruction in patients with temporomandibular joint (TMJ) involvement of polyarthritides. PATIENTS AND METHODS: Forty-three patients with TMJ involvement of polyarthritides were included. TMJ resting pain, tenderness to palpation, pressure pain threshold, pain on mandibular movement, and anterior open bite were assessed. TMJ synovial fluid samples and plasma were obtained for analysis of IL-1beta, IL-1ra, and sIL-1RII. RESULTS: IL-1beta was detected in 18% of the synovial fluid samples and in 44% of the plasma samples. The concentrations of IL-1ra in plasma were lower than in the synovial fluid, whereas the opposite condition was found for sIL-1-RII. IL-1ra in synovial fluid and plasma was associated with low intensity of TMJ pain. sIL-1RII in synovial fluid was associated with low degree of anterior open bite, whereas sIL-1RII in plasma was associated with widespread musculoskeletal pain, TMJ pain and tenderness, and decreased pressure pain threshold over the TMJ. CONCLUSION: IL-1ra and sIL-1RII are present in different proportions in TMJ synovial fluid and blood plasma from patients with TMJ involvement of polyarthritis. Both of these molecules seem to influence the clinical features of these forms of TMJ inflammation.     

Human temporomandibular joint and myofascial pain biochemical profiles: a case-control study

Neurobiological mechanisms of human musculoskeletal pain are poorly understood. This case-control study tested the hypothesis that biomarkers within temporomandibular muscle and joint disorders (TMJD) subjects' masseter muscles or temporomandibular joint (TMJ) synovial fluid correlate with plasma biomarker concentrations. Fifty subjects were recruited and categorized into TMJD cases (n=23) and pain-free controls (n=27) at the University of Minnesota School of Dentistry. Prior to specimen collection, pain intensity and pressure pain threshold masseter muscles and the TMJs were assessed. We collected venous blood; biopsied masseter muscle; and sampled TMJ synovial fluid on the subjects' side of maximum pain intensity. We assayed these tissues for the presence of nerve growth factor (NGF), bradykinin (BK), leukotreine B(4) (LTB(4) ) and prostaglandin E(2) (PGE(2) ), F(2) -isoprostane (F(2) I) and substance P (SP). The data was analyzed using Spearman Correlation Coefficients. We found that only plasma concentrations of bradykinin statistically correlated with synovial fluid concentrations (ρ=-0·48, P=0·005), but no association was found between pain intensities. The data suggests that biomarkers used to assess TMJD need to be acquired in a site-specific manner. We also discovered that F(2) I concentrations were associated with muscle pain intensity and muscle pressure pain threshold (PTT) (β=0·4, 95%CI: 0·03-0·8) and joint PPT (β=0·4, 95%CI: 0·07-0·8) suggesting that muscle oxidative stress is involved in myofascial pain and that F(2) -I may be a biomarker for myofascial pain.     

Temporomandibular joint pain: relationship to internal derangement type, osteoarthrosis, and synovial fluid mediator level of tumor necrosis factor-alpha

OBJECTIVES: The purpose of this study was to investigate whether patients with temporomandibular joint (TMJ)-related pain classified as capsulitis/synovitis may be linked to magnetic resonance imaging (MRI) findings of internal derangement, osteoarthrosis, or the synovial fluid aspirate findings of tumor necrosis factor-alpha (TNF-alpha) level. STUDY DESIGN: The study comprised 23 patients with temporomandibular disorders (TMD), who had nonchronic pain (pain onset < or =6 months) and a unilateral TMJ-related diagnosis of capsulitis/synovitis. Bilateral sagittal and coronal magnetic resonance images were obtained to establish the presence or absence of internal derangement, osteoarthrosis, or both. TMJ synovial fluid aspirates were obtained from the pain and contralateral nonpain sides to determine the TNF-alpha level. RESULTS: Comparison of the TMJ side-related data showed a significant relationship between the clinical TMD diagnosis of capsulitis/synovitis and the MRI diagnoses of TMJ internal derangement (P =.002) and of TMJ internal derangement type (P =.04). The mean TNF-alpha level in synovial fluid aspirates from TMJs assigned a clinical TMD diagnosis of capsulitis/synovitis was significantly higher than in those obtained from contralateral nonpain sides (P =.001). There was no correlation between the clinical diagnosis of capsulitis/synovitis and the MRI diagnosis of TMJ osteoarthrosis (P =.13) or between the MRI diagnosis of TMJ osteoarthrosis and that of TMJ internal derangement (P =.70) or TMJ internal derangement type (P =.33). CONCLUSIONS: The results suggest that the TMJ pain condition of capsulitis/synovitis is related to TMJ-side specific MRI diagnoses of internal derangement and internal derangement type, and synovial fluid aspirate findings of TNF-alpha level. The data confirm the concept of elevated mediator level as a diagnostic approach for patients presenting with TMJ-related pain. MRI and synovial fluid aspirates may be used as diagnostic methods for evaluating TMJ-related pain conditions.     

Oxidative stress-induced DNA damage in the synovial cells of the temporomandibular joint in the rat

Synovial hyperplasia is a feature of degenerative temporomandibular joint (TMJ) disease. However, the mechanism by which hyperplasia progresses in the TMJ is unknown. Based on the hypothesis that the oxidative stress generated by mechanical loading causes degenerative changes in the TMJ synovium, we investigated the generation of the highly reactive species, peroxynitrite, and the occurrence of DNA damage in the synovium. After condylar hypermobility of rat TMJs, a marker of peroxynitrite, nitrotyrosine, was localized to the nuclei and cytoplasm of the synovial lining cells and fibroblasts in synovitis-induced TMJ. DNA single-strand breaks were found in the nuclei of the synovial cells only after enzyme treatment, whereas DNA double-strand breaks were not detected. These findings indicate that condylar hypermovement induces the proliferation of synovial cells, and suggest that oxidative stress leads to the progression of synovial hyperplasia via DNA damage of the synovial cells in TMJs after mechanical loading.     

关节液蛋白含量与颞下颌关节疼痛患者影像学特征的对照研究

目的　探讨关节液中的蛋白浓度与关节影像学特征性表现及疼痛的关系。方法　采用磁共振成像 (MRI)金标准对4 0例单侧颞下颌关节 (TMJ)疼痛患者进行结构紊乱、骨关节炎及关节渗液的诊断 ,并在关节上腔冲洗治疗时收集关节液标本 ,以不存在结构紊乱、骨关节炎及关节渗液的关节液标本为对照 ,15侧无症状志愿者的关节液为正常对照 ;采用双金鸡宁酸法检测关节液中蛋白浓度。结果　患者关节液中蛋白含量的高低与结构紊乱、关节渗液及骨关节炎均无相关性 ;患者关节液中蛋白含量与正常人蛋白含量无差异。结论　关节液中的蛋白水平不能反映在影像学上代表关节炎症的结构紊乱、骨关节炎及渗出液关节的炎症状态及疼痛。     

Up-regulation of interleukin-6 and vascular endothelial growth factor-A in the synovial fluid of temporomandibular joints affected by synovial chondromatosis

Our aim was to explore important inflammatory mediators for synovial chondromatosis in the temporomandibular joints (TMJs) by analysing synovial fluid. Samples were collected from 10 patients with unilateral synovial chondromatosis of the TMJ. Control samples were obtained from 11 subjects with no symptoms in the TMJ. Concentrations of aggrecan, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8 (CXCL8), IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF)-A were measured in the samples of synovial fluid, and the results in the two groups compared. The tissues from the affected TMJ were examined histologically and immunohistochemically. Of the proteins evaluated, the concentrations of aggrecan, IL-6, and VEGF-A were significantly higher in the group with synovial chondromatosis. The immunohistochemical analysis showed that the synovial cells around the osteocartilaginous nodules were vigorously expressing VEGF-A.     

Temporal changes in inflammatory mediator concentrations in an adjuvant model of temporomandibular joint inflammation

AIMS: To determine temporal changes in the concentrations found in the temporomandibular joint (TMJ) and trigeminal ganglion of 3 specific classes of inflammatory mediators commonly linked with conditions of joint inflammation. The intent was to determine whether concentrations of the neuropeptide calcitonin gene-related peptide (CGRP), the neurotrophin nerve growth factor (NGF), and the proinflammatory cytokines interleukin-1beta (IL1beta) and tumor necrosis factor-alpha (TNF-alpha) are altered in the trigeminal ganglion and TMJ tissues during various stages of adjuvant-induced inflammation of the rat TMJ. METHODS: Adult male rats received bilateral TMJ injection of complete Freund's adjuvant (CFA), while control rats did not receive CFA treatment. The trigeminal ganglion and TMJ tissues were collected at 2 days, and 2, 4, and 6 weeks postinjection and analyzed using either radioimmunoassay or enzyme-linked immunosorbent assay. RESULTS: In the trigeminal ganglion, both CGRP and NGF concentrations were significantly elevated in comparison to controls from 2 days to 4 weeks; however, the patterns of increase differed. Concentrations of each inflammatory mediator were significantly elevated in the TMJ tissues of CFA-injected animals at 2 days and continued to be significantly elevated throughout the 6-week period. CGRP content remained at peak levels from 2 days through 6 weeks, while peak content for NGF, IL-1beta, and TNF-alpha was found at 2 days through 2 weeks. CONCLUSION: The results suggest that the development of CFA-induced inflammation of the TMJ was accompanied by a variable increase in the concentration of different classes of inflammatory mediators in both the trigeminal ganglion and TMJ tissues, which implies that each class of inflammatory mediator may play a significant role during different stages in the onset and exacerbation of the inflammatory process.     

The expression of substance P in human temporomandibular joint samples: an immunohistochemical study

The expression of neuropeptide substance P was examined in 18 human temporomandibular joint (TMJ) samples with internal derangement of the TMJ, and in 10 control specimens. The examination was carried out using an immunohistological technique, using paraffin-embedded tissue and specific anti-human substance P polyclonal antibody. We noted five characteristic distribution patterns of substance P expression: at the nerves' fibre bundles in the connective tissues of the anterior and/or posterior attachment; around the blood vessels in the attachments; at the margin of the TMJ disc and synovial membrane layer; on the surface of hypertrophic synovial membranes with inflammation and proliferation; and around the newly formed capillaries in the TMJ discs. In TMJs with internal derangement associated with severe pain, we found distinct substance P expression in most of the specimens. The expression was particularly intense at the margin of the TMJ disc and synovial membrane layer, on the surface of hypertrophic synovial membranes and around the newly formed capillaries in the TMJ discs. The clinical symptoms of internal derangement of the TMJ are thought to be associated with the degree of synovitis. We conclude that the expression of substance P seems to be closely related to histopathological changes of the human TMJ with internal derangement.     

Identification of prostaglandin E2 and leukotriene B4 in the synovial fluid of painful, dysfunctional temporomandibular joints

It has been hypothesized that prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) should be present in the synovial fluid of inflamed, dysfunctional temporomandibular joints. An assay to identify PGE2 and LTB4 and platelet-activating factor (PAF) was used, and a strong correlation between the levels of these lipid mediators of pain and inflammation and an index of clinical joint pathology was found.