Temporomandibular joint imaging: current clinical applications, biochemical comparison with the intervertebral disc and knee meniscus, and opportunities for advancement.

Temporomandibular disorders encompass multiple pathologies of the temporomandibular joint that manifest as middle/inner ear symptoms, headache, and/or localized TMJ symptoms. There is an important although somewhat limited role of imaging in the diagnostic evaluation of temporomandibular disorders. In this manuscript, we provide a comprehensive review of TMJ anatomy, outline potentially important features of TMJ disc ultrastructure and biochemistry in comparison with the intervertebral disc and knee meniscus, and provide imaging examples of the TMJ abnormalities currently evaluable with MRI and CT. In addition, we provide an overview of emerging and investigational TMJ imaging techniques in order to encourage further imaging research based on the biomechanical alterations of the TMJ disc.

Effect of TLR4/MyD88 signaling pathway on expression of IL-1ß and TNF-α in synovial fibroblasts from temporomandibular joint exposed to lipopolysaccharide.

Accumulating evidence from previous studies suggested that interleukin-1 (IL-1ß) and tumor necrosis factor-α (TNF-α) play an important role in pathogenesis of temporomandibular disorders (TMD). However, the cell surface receptors and the intracellular signal pathways leading to these cytokines expression are not fully understood. In the current study, we investigated the roles of Toll-like receptor 4 (TLR4) and its adaptor myeloid differentiation factor 88 (MyD88) in the expression of IL-1ß and TNF-α in synovial fibroblasts (SFs) separated from rat temporomandibular joint (TMJ) with lipopolysaccharide (LPS) stimulation. The results showed that treatment with LPS could increase TLR4, MyD88, IL-1ß, and TNF-α expression at both mRNA and protein levels. In addition, increased expression of IL-1ß and TNF-α could be blocked by treatment with TAK-242, a blocker of TLR4 signaling, and also by MyD88 inhibitory peptide (MIP). These findings suggested that maybe TLR4/MyD88 signal transduction pathway participates in enhanced expression of IL-1 and TNF-α in patients with TMD. The activation of TLR4/MyD88 signal transduction pathway which results in production of proinflammatory factors may play a role in the pathogenesis of TMD.

Cytokines in healthy temporomandibular joint synovial fluid.

Analysis of temporomandibular joint (TMJ) synovial fluid may elucidate the aetiology of temporomandibular disorders and arthritic conditions, as well as the inflammatory mechanisms involved. Knowledge about healthy synovial fluid is necessary to understand TMJ pathologies. We aimed to quantify the proinflammatory cytokines interleukin (IL)-1ß, IL-2, IL-6 and tumour necrosis factor (TNF), and the anti-inflammatory cytokines IL-10 and interferon (IFN)-γ in healthy TMJ synovial fluid to serve as reference values for future studies on TMJ pathologies. Twenty healthy, young adult volunteers without temporomandibular dysfunction were included. Bilateral synovial fluid samples were obtained using the push-pull technique with hydroxocobalamin described by Alstergren in 1999. Cytokines were quantified with Luminex multiplex assays and compared using nonparametric statistical analysis. No serious adverse effects were reported. Of 40 possible samples, 14 fulfilled the strict sampling criteria and were included in the analysis. Cytokine values (reported as medians with interquartile ranges) were as follows: TNF, 23 (13-37) pg mL(-1) ; IL-2, 1·8 (0-22) pg mL(-1) ; and INF-γ, 10 (0-47) pg mL(-1) . IL-1ß, IL-6 and IL-10 were almost undetectable. In addition, TNF and INF-γ cytokine levels correlated. We demonstrated that TNF was consistently detected and IFN-γ and IL-2 sporadically detected in the TMJ synovial fluid of healthy individuals using the hydroxocobalamin method and a multiplex assay. The cytokines IL-10, IL-1ß and IL-6 were barely detectable in this sample of healthy TMJs.

Efficient Delivery of siRNA via Tetrahedral Framework Nucleic Acids: Inflammation Attenuation and Matrix Regeneration in Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is the most common and severe subtype of temporomandibular disease characterized by inflammation and cartilage matrix degradation. Compared with traditional conservative treatment, small interfering RNAs (siRNAs) have emerged as a more efficient gene-targeted therapeutic tool for TMJOA treatment. Nuclear factor kappaB (NF-κB) is a transcription factor orchestrating the inflammatory processes in the pathogenesis of TMJOA. Employing siRNA-NF-κB could theoretically control the development of TMJOA. However, the clinical applications of siRNA-NF-κB are limited by its structural instability, poor cellular uptake, and short TMJ retention. To overcome these shortcomings, we developed a tetrahedral framework nucleic acid (tFNA) system carrying siRNA-NF-κB, named Tsi. The results indicated that Tsi exhibited excellent structural stability and excellent cellular uptake efficiency. It also demonstrated a superior NF-κB silencing effect over siRNA alone, attenuating the activation of NF-κB and upregulating the NRF2/HO-1 pathway. This system effectively reduced the release of inflammatory factors and reactive oxygen species (ROS), inhibiting cellular oxidative stress and apoptosis. In vivo, Tsi displayed enhanced TMJ retention capacity in comparison to siRNA alone and offered significant protective effects on both the cartilage matrix and subchondral bone, presenting a promising approach for TMJOA treatment.

Computational characterization of the porous-fibrous behavior of the soft tissues in the temporomandibular joint.

The prevalence and severity of temporomandibular joint (TMJ) disorders have led to growing research interest in the development of new biomaterials and medical devices for TMJ implant designs. In computational designs, however, the time and stretch direction dependences of the TMJ soft tissues behavior are not considered and they are frequently based on measurements taken from non-human species or from joints that differ markedly from the human TMJ. The aim of this study was to accurately characterize the porous-fibrous properties of the TMJ soft tissues by simulating previously published experimental tests, to assist professionals in the design of new TMJ implants. To that end, material parameters were determined assuming a uniform fiber orientation throughout the entire sample. This assumption was then tested by comparing these results with those of considering multiple regions and distinct fiber orientations in each sample. Our findings validated the use of a transversely isotropic hyperelastic material model to characterize the direction dependent behavior of TMJ soft tissues and its combination with porous hyperfoam material models to mimic the compressive response of the TMJ disc. In conclusion, constitutive model proposed accurately reproduce the mechanical response of the TMJ soft tissues at different strain rates and stretch directions.

The Optimal Regimen for the Treatment of Temporomandibular Joint Injury Using Low-Intensity Pulsed Ultrasound in Rats with Chronic Sleep Deprivation.

Low-intensity pulsed ultrasound (LIPUS) is an emerging physical therapy for the treatment of early temporomandibular joint injury and has a good effect on promoting cartilage and subchondral bone tissue repair. However, the best LIPUS intensity and treatment duration remain unclear. This study is aimed at observing the preventive and therapeutic effects of different modes of LIPUS and at identifying the optimal LIPUS treatment regimen for temporomandibular joint injury. In the present study, rat models of temporomandibular joint injury were established using a chronic sleep deprivation (CSD) method, and the effect of LIPUS as intensities of 30, 45, and 60 mW/cm2 was observed at 7, 14, and 21 days. After CSD, the condylar cartilage of the rats demonstrated variable degrees of surface roughening, collagen fiber disarrangement or even partial exfoliation, decreased proteoglycan synthesis and cartilage thickness, decreased chondrocyte proliferation, decreased type 2 collagen (COL-2) expression, and increased matrix metalloproteinase- (MMP-) 3 expression at all three time points. When the rats with CSD received different intensities of LIPUS treatment, the pathological changes were alleviated to various extents. The groups receiving 45 mW/cm2 LIPUS showed the most significant relief of cartilage damage, and this significant effect was observed on days 14 and 21. These results demonstrated that LIPUS can effectively inhibit CSD-induced condylar cartilage damage in rats, and LIPUS treatment at an intensity of 45 mW/cm2 for at least 2 weeks is the optimal regimen for temporomandibular joint injury.

Tumoral calcium pyrophosphate dihydrate crystal deposition disease of the temporomandibular joint: identification on crystallography.

This paper reports a case of calcium pyrophosphate dihydrate (CPPD) crystal deposition in the temporomandibular joint (TMJ) of a 59-year-old man with the chief complaint of severe pain in the left TMJ. On CT a radiopaque area was seen around the condylar process of the left TMJ with irregular destructive bony changes. A provisional diagnosis of crystalline-induced arthritis was made on histopathology of a biopsy specimen. Electron probe microanalysis (EPMA), scanning electron microscopy (SEM) and X-ray diffraction showed both CPPD and hydroxyapatite (HA) in the crystalline materials. Identification of these two types of crystal in crystal deposition disease of TMJ, using crystallography, is discussed.

Localization of CD44 and hyaluronan in the synovial membrane of the rat temporomandibular joint.

Previous studies have pointed out a lack of adhesion structures in the synovial lining layer of the rat temporomandibular joint (TMJ) despite showing an epithelial arrangement. CD44, a major cell adhesion molecule, plays crucial roles as an anchor between cells and extracellular matrices by binding hyaluronan (HA) for the development of organs or the metastasis of tumors. The present study examined the localization of CD44 in the synovial membrane of the rat TMJ by immunocytochemistry for OX50, ED1, and Hsp25, which are markers for the rat CD44, macrophage-like type A, and fibroblast-like type B synoviocytes, respectively. Histochemistry for HA-binding protein (HABP) was also employed for the detection of HA. OX50 immunoreactions were found along the cell surface and, in particular, accumulated along the surface of the articular cavity. Observations by a double immunostaining and immunoelectron microscopy revealed that all the OX50-immunopositive cells were categorized as fibroblastic type B cells, which had many caveolae and a few vesicles reactive to intense OX50. However, the macrophage-like type A cells did not have any OX50 immunoreaction in the synovial lining layer. A strong HABP reaction was discernable in the extracellular matrix surrounding both OX50-positive and -negative cells in the synovial lining layers, exhibiting a meshwork distribution, but weak in its sublining layer. This localization pattern of CD44 and HABP might be involved in the formation of the epithelial arrangement of the synovial lining layer. Furthermore, OX50 immunonegativity in the type A cells suggests their low phagocytotic activity in the rat TMJ under normal conditions.

Small proteoglycans from different regions of the fibrocartilaginous temporomandibular joint disc.

Proteoglycans were isolated from two zones--the periphery and the inner zone--of bovine temporomandibular joint articular discs and separated into two pools by gel-filtration. Proteoglycans in the low molecular mass pool were further resolved by hydrophobic affinity chromatography into two groups identified by cyanogen bromide peptide analysis, amino acid analysis and amino-terminal sequence analysis as PGI (biglycan) and PGII (decorin). These two proteoglycans were isolated in approximately equal proportions from the 'inner' disc tissue but PGII predominated in the 'outer' tissue. Direct chemical analysis showed that the glycosaminoglycan chains on both PGI and PGII were high in iduronate (64-68% of total uronic acid). The dermatan sulfate chains on proteoglycans from the inner disc tissue were longer than those from the outer tissue. Comparison of the galactosamine contents of the intact proteoglycans with electrophoretic mobilities of the isolated dermatan sulfate chains showed that the PGI from the disc carries two dermatan sulfate chains. Inclusion of disc DS-PGI in a solution of soluble type I collagen lengthened the lag-phase, steepened the turbidity-time curve and increased the final opacity attained during fibril formation in vitro. The median fibril diameter and the range of diameters were both higher in the presence of DS-PGI. By contrast, disc DS-PGII reduced the slope of the turbidity-time curve but had little effect on the final turbidity or the fibril diameter.

Immunocytochemical localization of MAPKAPK-2 and Hsp25 in the rat temporomandibular joint.

One series of our research has shown an intense expression of immunoreaction for heat shock protein 25 (Hsp25) in various cellular elements in the rat temporomandibular joint (TMJ). This protein is the major substrate of mitogen-activated protein kinase-activated protein kinase-2 (MAPKAPK-2), which mediates an intracellular stress-activated signaling pathway to stimulate cytosolic actin reorganization under various stresses. The present study was undertaken to examine the localization of MAPKAPK-2 in the rat TMJ by immunocytochemical techniques. Furthermore, confocal microscopy with double staining was employed to demonstrate the colocalization of MAPKAPK-2 and Hsp25. Immunocytochemistry for MAPKAPK-2 showed an intense immunoreaction in the cytoplasm of the synovial lining cells, the endothelial cells, and the fibroblasts in the synovial membrane of the rat TMJ. Double immunostaining under a confocal microscope succeeded in demonstrating the colocalization of MAPKAPK-2 and Hsp25 immunoreactions in the cytoplasm of fibroblastic type B synoviocytes in the TMJ. On the other hand, the macrophage-like type A-cells expressed MAPKAPK-2 immunoreactions but lacked Hsp25 immunoreactivity. The cells in the articular disk and the chondrocytes in the maturative and hypertrophic layer of the mandibular cartilage also showed intense immunoreactions for MAPKAPK-2 and Hsp25. In addition to cytoplasmic localization, MAPKAPK-2 immunoreactions were found in the nucleus of some synovial lining cells, cells in the articular disk, and chondrocytes. Current observations imply the presence of the phosphorylation of Hsp25 via activated MAPKAPK-2 in the cytoplasm. MAPKAPK-2 and Hsp25 possibly participate in the induction of cytoskeletal changes to the various cellular elements in rat TMJ under normal conditions.

mu-Opioid receptor mRNA expression and immunohistochemical localization in the rat temporomandibular joint.

This study was undertaken to examine the presence and distribution of the mu-opioid receptor (MOR) in the non-inflamed rat temporomandibular joint (TMJ) using non-radiographic in situ hybridization at the mRNA level and immunohistochemistry at the protein level. MOR mRNA and MOR-like immunoreactivity (MOR-LI) were found around the small blood vessels in the anterior part of the synovial membrane. The number of MOR mRNA signals in the anterior synovial membrane was significantly higher than that in the posterior part. Morphologically, MOR mRNA and MOR-LI were localized in amorphous materials considered to be nervous tissue, as well as some cell types considered to be macrophages, mast cells and endothelial cells. The present study showed the distribution of MOR in the rat TMJ synovial membrane and suggests that the opiate system plays an important role in endogenous analgesia in the TMJ.

Type VI collagen periodic fibrils in the synovium of the mouse temporomandibular joint.

Immunohistochemical staining with anti-type VI collagen antibody was strongly positive in the intimal layer and moderately positive in the subsynovium. After treatment with 20 mM ATP, numerous structures with a periodicity of 100 +/- 10 nm (type VI collagen fibrils) appeared around the synovial cells. As the periodic dark bands were stained by ruthenium red, proteoglycan(s) or glycosaminoglycan(s) were probably associated with the type VI collagen fibrils. When the tissue was digested with testicular hyaluronidase before ATP treatment, the periodic fibrils were not found, and only a filamentous network of 100-nm interval was seen around the cells. Thus, type VI collagen is abundant in the synovium of the mouse mandibular joint and is associated with proteoglycans or glycosaminoglycans, which might have a role in its formation.

Soluble tumour necrosis factor receptors in synovial fluids from temporomandibular joints with painful anterior disc displacement without reduction and osteoarthritis.

The objective of this study was to detect soluble-form tumour necrosis factor receptors (sTNFRs) in temporomandibular joint (TMJ) synovial fluid aspirates, and to compare the sTNFR concentrations between painful anterior disc displacement without reduction and osteoarthritis (ADDwoR/OA) and asymptomatic TMJs. Synovial fluid was sampled from the superior TMJ cavity of 11 painful ADDwoR/OA cases (mean age: 36.9 years) and 10 asymptomatic females (mean age: 24.7 years) by diluted aspiration. The concentrations of sTNFR-I and -II in the synovial fluid were measured using human sTNFR-I and -II enzyme-linked immunosorbent assays. The total protein concentrations in synovial fluids were measured using a bicinchoninic acid protein assay kit. All data were normalised to the total protein concentration of each sample.Two-way factorial analysis of variance and post hoc multiple comparison revealed that: (1). mean normalised sTNFR-I and -II concentrations were higher in TMJ synovial aspirates from ADDwoR/OA patients than from healthy controls; (2). in the ADDwoR/OA patients and the healthy controls, the sTNFR-I concentration in TMJ synovial aspirates was higher than the sTNFR-II concentration; and (3). high TMJ synovial aspirate sTNFR-II seemed to be associated with less TMJ pain and a less restricted range of mouth opening in the ADDwoR/OA patients. The concentrations of sTNFRs in TMJ synovial fluid are higher in the presence of painful ADDwoR/OA, which could modulate intracapsular inflammation.

Age-associated changes in decorin in rat mandibular condylar cartilage.

The small proteoglycan decorin strongly binds the fibrils of collagen types I and II; this interaction is thought to play a part in the maintenance of tissue integrity and biomechanical properties. In limb articular cartilage, there is evidence that decorin synthesis increases with age and that it is elevated in response to increased loading or in osteoarthritic cartilage. The aim here was to characterize the presence and relative amount of decorin in the condylar cartilage of the temporomandibular joint (TMJ) with maturation by Western blotting, and to assess its tissue localization by immunohistochemistry. Comparative data were obtained from tibial articular cartilage, which has been extensively studied. Cartilage from the mandibular condyle and tibial plateau was harvested from 24-day-old (growing) and 161-day-old (young adult) female Sprague-Dawley rats. In growing animals, decorin appeared slightly more abundant in the mandibular condylar cartilage than in articular cartilage, whereas in young adult animals the decorin content in the TMJ cartilage was noticeably less than in limb articular cartilage. Although there was an increase in decorin abundance with age at the TMJ, the increase in decorin with age in limb articular cartilage was considerably more pronounced. These data indicate that, although decorin is present in mandibular condylar cartilage, its abundance in adults is less than in limb articular cartilage; thus, maturation-associated changes may be dissimilar in magnitude from those documented for limb articular cartilage.

Morphological and biochemical evidence for elastic fibres in the Syrian hamster temporomandibular joint disc.

Elastic fibres are considered to be important for the normal biomechanical functions of the TMJ. The objective here was to correlate morphological evidence for the presence of elastic fibres in discal tissues with biochemical evidence for elastin. For light microscopy, the joints were removed en bloc, processed for paraffin embedding, sectioned and stained with resorcin-fuchsin. For biochemical study, a radioimmunoassay for desmosine was used to estimate the amount of elastin in excised articular discs. The histological preparations showed that numerous elastic fibres were present in various areas of the disc and in some of the discal attachments to surrounding bone. Radioimmunoassay also indicated that elastin was present in these tissues. Therefore, the biochemical findings support the morphological in suggesting that elastic fibres are present in the articular disc of the hamster TMJ.

Specific properties of the extracellular chondroitin sulphate proteoglycans in the mandibular condylar growth centre in pigs.

The developing condylar cartilage of the temporomandibular joint responds to changes in load by adaptive growth. Because local regulatory events taking place during growth processes are not well understood, investigation of extracellular matrix composition could provide new information about which matrix molecules are involved in the regulation of growth processes in this avascular tissue. The large chondroitin sulphate-rich proteoglycans in the mandibular condyle were compared to the proteoglycans in the weight-bearing femoral condyle of juvenile domestic pigs with respect to their buoyant density, chemical composition and immunological identity after isolation by dissociative extraction and CsCl density-gradient centrifugation. The distribution of these proteoglycans was studied in cryosections of mandibular condyle by immunohistochemistry using polyclonal antibodies produced against pig large proteoglycans. In the mandibular condyle, predominantly in the articular zone, the relative amount of proteoglycans with a low glycosaminoglycan content was greater than in femoral cartilage. The large proteoglycan immunologically related to aggrecan gave a protein core of 450 kDa after enzymatic deglycosylation and clearly possessed less keratan sulphate than in femoral aggrecan. Furthermore, the mandibular tissue contained another large proteoglycan with a protein core of 550 kDa after enzymatic deglycosylation, which was immunologically related to the fibroblast-like versican. Immunohistochemistry showed aggrecan increasing in amount inferiorly. In contrast, "versican' was exclusively found in the fibrous and differentiation layers. Aggrecan is mainly responsible for shock absorption and versican and its homologues may be involved in the control of cell proliferation and differentiation. Thus the matrix components of the mandibular condyle seem to be adapted to its special functional needs including parallel articulation and growth.

Morphologic, microscopic, and immunohistochemical investigations into the function of the primate TMJ disc.

The distribution and arrangement of extracellular matrix proteins were examined in the primate temporomandibular joint disc and posterior attachment using a combination of light microscopic, immunohistochemical, and biochemical techniques. The band areas of the disc contain a complex collagenous (type I) fiber network consisting of a mediolaterally directed fiber bundle system that interlaces or becomes continuous with an anteroposteriorly directed collagenous fiber array that runs through the intermediate zone. Thin, branching, elastic fibers are a significant component of the disc and are generally oriented parallel to the collagenous fiber network. Interfibrillar spaces in band areas contain numerous chondrocytes encased within a matrix that is rich in a high molecular weight, predominantly chondroitin-sulfate proteoglycan and type II collagen. The intermediate zone appears tendinous in its construction and is composed of anteroposteriorly oriented elastic and collagenous fibers, scattered chondrocytes, and reduced amounts of chondroitin-sulfate proteoglycan and type II collagen. The posterior attachment is composed of fibrocytes, larger caliber elastic fibers, loosely organized type I collagenous fibers, and low molecular weight dermatan-sulfate proteoglycan. These results indicate that the primate temporomandibular joint disc is a microheterogenous tissue with distinct regional specializations.

Neural structures within the sheep temporomandibular joint.

To better understand pathologic processes associated with arthritis of the temporomandibular joint (TMJ), detailed information on the innervation of TMJ tissues in normal as well as arthritic joints is needed. The aim of this study was to describe the normal innervation of the sheep TMJ in preparation for using this animal as a model for the study of the effects of arthritis on joint innervation. The macroscopic and microscopic appearance plus the distribution of neural structures within the TMJ were examined using fluorescence histochemistry (glyoxylic acid), immunohistochemistry (calcitonin gene-related peptide), silver, and gold chloride techniques. Joints from 10 mature merino sheep were studied. Calcitonin gene-related peptide-immunoreactive nerve fibers were found in the capsule and the synovial membrane, but not in the disc. Nerve bundles and single nerve fibers in the capsule, synovial membrane, and the peripheral 2 to 3 mm of the disc were stained by glyoxylic acid. Ruffini, paciniform-type, and Golgi organ nerve endings plus free nerve endings were located in the capsule, with the highest density of nerve endings occurring at the site of attachment of the disc to the capsule. The highest density of neural structures (using gold chloride) was in the posterior part of the joint. The highest density of autonomic fibers (using glyoxylic acid) was in the anterior capsule. The highest density of sensory fibers (using calcitonin gene-related peptide) was in the synovial and subsynovial tissues of the anterior capsule. These results confirm the existence of autonomic and sensory nerves in the capsule, synovial membrane, and peripheral disc in healthy adult sheep.

Effects of adjuvant on neuropeptide-like immunoreactivity in the temporomandibular joint and trigeminal ganglia.

To study the role of the nervous system in temporomandibular joint arthritis, substance P-, calcitonin gene-related peptide-, and neuropeptide Y-like immunoreactivity in the trigeminal ganglia and temporomandibular joint of rats was examined. Arthritis was induced in female Lewis rats through bilateral injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil into the temporomandibular joint. Control rats received paraffin oil via the same route. Tissues were collected for neuropeptide extraction 28 days after injection and analyzed by radioimmunoassay and reverse-phase high-performance liquid chromatography. Calcitonin gene-related peptide was significantly increased in the arthritic trigeminal ganglia. Substance P, calcitonin gene-related peptide, and neuropeptide Y in the arthritic temporomandibular joint were significantly increased as compared to controls. The results of this study show that sensory and sympathetic neuropeptides may possibly be associated with the development of arthritis in the temporomandibular joint of rats.

Concentrations of neuropeptides substance P, neurokinin A, calcitonin gene-related peptide, neuropeptide Y and vasoactive intestinal polypeptide in synovial fluid of the human temporomandibular joint. A correlation with symptoms, signs and arthroscopic findings.

Arthroscopy was performed on 18 patients (19 joints) with temporomandibular joint arthropathy. Arthroscopic investigation revealed that 12 patients had disk derangement, including 3 patients with rheumatoid arthritis. Six patients had osteoarthrosis, including one patient with rheumatoid arthritis. Synovial fluid content of substance P-like immunoreactivity (SP-LI), neurokinin A (NKA-LI), calcitonin gene-related peptide (CGRP-LI), neuropeptide Y (NPY-LI) and vasoactive intestinal polypeptide (VIP-LI) were analysed using radioimmunoassay technique. All peptides analysed were found, although in various concentrations, in the different joints. There were no significant differences in concentrations of the peptides in the synovial fluid between patients in the various groups. No significant correlation was found between clinical symptoms and signs, arthroscopic findings, or use of analgesic/anti-inflammatory medication versus concentrations of peptides in the synovial fluid. In comparison with earlier findings in the knee joint significantly higher concentrations of SP-LI, CGRP-LI and NPY-LI were found in the TMJ.