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Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) have been used as adjuncts to temporomandibular joint (TMJ) arthrocentesis but without any high-quality evidence. This systematic review collated data from published randomised controlled trials (RCTs) to provide level-1 evidence on its efficacy. Trials published on the databases of PubMed, Scopus, Embase, CENTRAL, and Web of Science up to 4 August 2023 and comparing intra-articular PRP/PRF with control after TMJ arthrocentesis were eligible. Primary outcomes were pain and maximal mouth opening (MMO). Twelve RCTs were included. Pooled analysis showed that pain scores were significantly reduced with the use of PRP/PRF as compared with control at one month (MD: -0.96 95% CI: -1.58 to -0.35 I 2  = 86%), three months (MD: -1.22 95% CI: -1.86 to -0.59 I 2  = 85%), and ≥six months (MD: -1.61 95% CI: -2.22 to -1.00 I 2  = 88%). Similarly, MMO was significantly improved in the PRP/PRF group at one month (MD: 2.40 95% CI: 1.02 to 3.77 I 2  = 88%), three months (MD: 3.17 95% CI: 1.63 to 4.72 I 2  = 91%), and ≥six months (MD: 2.98 95% CI: 1.86 to 4.10 I 2  = 75%) as compared with the control group. Subgroup analysis for PRP and PRF failed to show any difference in outcomes. Moderate quality evidence suggests that PRP and PRF may significantly improve pain and MMO when used as adjuncts to TMJ arthrocentesis. Due to the small effect size, the clinical significance of the results is questionable. The high heterogeneity in PRP/PRF preparation methods is a significant limitation., (Copyright © 2024 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Hyaluronic acid (HA) is the main component of the temporomandibular joint (TMJ) synovial fluid. Arthritis in temporomandibular disorders (TMDs) disrupts HA metabolism, resulting in shorter polymeric chain predominance and increased friction. Intra-articular injections of HA supplement the larger molecules of this glycosaminoglycan, and the platelet-rich plasma (PRP) delivered in this way releases growth factors, suppressing inflammation. This PRISMA-compliant PROSPERO-registered (CRD42024564382) systematic review aimed to assess the validity of mixing HA with PRP in the injectable treatment of TMJ disorders. We searched the medical literature for eligible randomized clinical trials using BASE, Google Scholar, PubMed and Scopus engines on 9 May 2024, with no time frame limit. Selected reports were assessed for risk of bias using the Cochrane RoB2 tool. Numerical data were collected on articular pain and mandibular mobility. We provided mean differences from baseline and between study and control groups at each observation point. The efficacy of TMD treatment with HA/PRP versus HA or PRP alone was assessed meta-analytically. Of 171 identified records, we selected 6 studies. In the 6-month follow-up, the mean advantage of PRP supplementation with HA was 2.52 (SE = 2.44; d = 0.83) mm and the benefit of adding PRP to HA was 1.47 (SE = 2.68; d = 0.34) mm in mandibular abduction. The pain-improvement scores were -1.33 (SE = 1.02; d = -1.05) and -1.18 (SE = 0.92; d = 0.80), respectively. Presumably, the HA/PRP range of therapeutic efficiency includes cases non-respondent to HA or PRP alone.

Hypertonic dextrose prolotherapy (DPT) has been reported to be effective for temporomandibular disorders (TMDs) in clinical trials but its overall efficacy is uncertain. To conduct a systematic review with meta-analysis of randomized controlled trials (RCTs) to synthesize evidence on the effectiveness of DPT for TMDs. Eleven electronic databases were searched from their inception to October, 2020. The primary outcome of interest was pain intensity. Secondary outcomes included maximum inter-incisal mouth opening (MIO) and disability score. Studies were graded by "Cochrane risk of bias 2" tool; if data could be pooled, a meta-analysis was performed. Ten RCTs (n = 336) with some to high risk of bias were included. In a meta-analysis of 5 RCTs, DPT was significantly superior to placebo injections in reducing TMJ pain at 12 weeks, with moderate effect size and low heterogeneity (Standardized Mean Difference: - 0.76; 95% CI - 1.19 to - 0.32, I 2  = 0%). No statistically significant differences were detected for changes in MIO and functional scores. In this systematic review and meta-analysis, evidence from low to moderate quality studies show that DPT conferred a large positive effect which met criteria for clinical relevance in the treatment of TMJ pain, compared with placebo injections.Protocol registration at PROSPERO: CRD42020214305., (© 2021. The Author(s).)

Local joint inflammation plays an important role in the pathogenesis of temporomandibular joint (TMJ) osteoarthrosis (TMJOA). Yohimbine, an alpha-2 adrenergic receptor antagonist, possesses anti-inflammatory properties; however, the ability of Yohimbine to protect against TMJOA-associated chondrocyte inflammation remains unclear. We conducted in vitro and in vivo analyses to investigate whether Yohimbine could ameliorate TMJOA-induced chondrocyte inflammation and to elucidate the mechanisms involved. Chondrocytes of TMJOA mice were stimulated with interleukin (IL)-1β or noradrenaline (NE), and the resulting production of inflammation-related factors was evaluated in the presence or absence of Yohimbine. Furthermore, two TMJOA mouse models were treated with Yohimbine and the therapeutic effect was quantified. NE (10 -6 M) triggered inflammatory cytokine secretion by TMJ chondrocytes, and Yohimbine suppressed IL-1β- or NE-induced IL-6 upregulation in TMJ chondrocytes with the nuclear factor (NF)-κB pathway inhibition. Yohimbine also ameliorated cartilage destruction in the TMJOA models. Interestingly, αmpT, a tyrosine hydroxylase inhibitor, reversed the effects of Yohimbine by activating the NF-κB pathway. Collectively, these findings show that Yohimbine ameliorated TMJ chondrocyte inflammation and the suppression of NF-κB pathway contributes to this effect.

Painful conditions of the temporomandibular joint (TMJ) are challenging to manage and most attempts often result in unsatisfactory outcomes. In such context, nanocarrier systems, such as polymeric micelles, have been showing encouraging results in solving therapeutic limitations. Poloxamers are widely used, especially PL 407, because of their high biocompatibility and approval by the Food and Drug Administration (FDA) for clinical use. 15-deoxy- Δ12,14 -prostaglandin J 2 (15d-PGJ 2 ) has shown important antinociceptive and anti-inflammatory activity. The present study evaluated the efficacy and viability of the micellar system of PL-15dPGJ 2 in a formalin-induced acute pain model in the temporomandibular joint of rats. The PL-15dPGJ 2 was prepared and characterized. The animals were pretreated with an intra-articular injection of PL-15dPGJ 2 followed by the formalin challenge. The nociceptive response was evaluated at different time-periods and the periarticular tissue and articular wash were collected for analysis. We found that intra-articular injection of PL-15d-PGJ 2 produced pain relief at lower concentrations and in a sustained manner compared with free 15d-PGJ 2 . Moreover, a strong anti-inflammatory effect was observed with decreased levels of key pro-inflammatory cytokines and modulation of the leukocyte migration process. Our findings suggest that 15d-PGJ 2 combined with a poloxamer micellar system provided clinical relevance in terms of bioavailability, long-lasting effect, and safe dosage. The formulation investigated herein is a promising micellar carrier system for managing pain conditions of the TMJ., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors stated explicitly that a patent relating to this study was requested entitled “Pharmaceutical composition of 15-deoxy-delta-(12,14)-prostaglandin J(2) in a poloxamer-based micellar system and its use for treatment of inflammatory conditions” n° WO2016044902-A1., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: The aim of this systematic review was to compile the latest evidence to assess the effectiveness of nonsteroidal anti-inflammatory drug(s) (NSAID) in patients with temporomandibular joint disorders (TMDs) in relieving pain. TMDs are a group of musculoskeletal disorders that affect the temporomandibular joint and/or masticatory muscles., Methods: After a literature review, a comprehensive search was conducted via Pubmed, Scopus, Google Scholar, and Cochrane databases with a systematic search strategy. The inclusion criteria were randomised controlled trials in humans, published in the last 50 years evaluating the effect of NSAIDs on TMDs. Although this duration chosen would potentially identify studies that have utilised outdated treatments, research methodology, and TMDs diagnostic criteria, and this has been considered before making clinical recommendation, it was used to advise future methodological changes necessary. The included studies were subjected to full-text review., Results: Out of 646 studies initially identified through searches, 12 were selected for full-text review of which 11 were included in the data synthesis. All 11 studies were randomised controlled trials. In total, 424 patients were included in this review. The earliest study included was 1996. Diagnostic criteria varied among all studies, and some did not specify enough signs and symptoms to construct a diagnosis. Intervention varied among all studies, as did the control. Nonspecific diagnosis, variable control groups, and heterogenous intervention protocols affected the outcome of this review. Despite the reduction of pain in the joint and/or masticatory muscles as well as improved range of motion, conclusive clinical recommendation could not be made., Conclusion: Heterogeneity did not allow for definitive conclusion; however, there was some evidence to support the use of NSAIDs in patients with TMDs for relief of pain. Further studies with strict, consistent diagnostic criteria and treatment are required., (© 2019 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

The temporomandibular joint (TMJ) is a fibrocartilaginous tissue critical for chewing and speaking. In patients with temporomandibular disorders (TMDs), permanent tissue loss can occur. Recapitulating the complexity of TMDs in animal models is difficult, yet critical for the advent of new therapies. Synovial fluid from diseased human samples revealed elevated levels of tumor necrosis factor alpha (TNF-alpha). Here, we propose to recapitulate these findings in mice by subjecting murine TMJs with TNF-alpha or CFA (Complete Freund's Adjuvant) in mandibular condyle explant cultures and by local delivery in vivo using TMJ intra-articular injections. Both TNF-alpha and CFA delivery to whole mandibular explants and in vivo increased extracellular matrix deposition and increased cartilage thickness, while TNF-alpha treated explants had increased expression of inflammatory cytokines and degradative enzymes. Moreover, the application of TNF-alpha or CFA in both models reduced cell number. CFA delivery in vivo caused soft tissue inflammation, including pannus formation. Our work provides two methods of chemically induced TMJ inflammatory arthritis through a condyle explant model and intra-articular injection model that replicate findings seen in synovial fluid of human patients, which can be used for further studies delineating the mechanisms underlying TMJ pathology., Competing Interests: The authors have declared that no competing interests exists.

Diabetes is a chronic degenerative disease that represent a major threat to public health worldwide. Once the disease is established, one of the major concerns about the diabetes complications is the development of neuropathy. This study established an experimental model that evaluates the effect of type 1 diabetes on nociceptive challenges in the temporomandibular joint (TMJ). Streptozotocin-induced type 1 (STZ 75 mg/Kg) diabetes inhibited the responsiveness of C-fibers nociceptors located in the TMJ of Wistar rats since seventh day after the disease induction. Diabetes-induced hyporesponsiveness of C-fibers nociceptors was associated with significantly reduction of protein level of neuropeptides Substance P and Calcitonin Gene Related Peptide. Diabetic animals pre-treated with Protein Kinase C (PKC)-α and -β inhibitor (GO6976) or PKC-β inhibitor (LY333531) significantly increased capsaicin-induced nociception in the TMJ higher protein levels of Na + /K + -ATPase pump in the trigeminal ganglia. On the other hand, although diabetes inhibits formalin-induced nociception higher protein levels of pro-inflammatory cytokine IL1-β and chemokine CINC-1/CXCL-1 were observed. Overall, the results of the present work suggest that diabetes causes a hyporesponsiveness of C-fiber and a potentialization of the inflammatory response which may result in the degenerative process of periarticular tissues without pain perception., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Introduction: Patients with tinnitus without an identifiable cause may have temporomandibular joint dysfunction and can be treated by an intra-articular injection of steroids., Objectives: The aim of this study was to determine the efficacy of temporomandibular steroids for treating patients with tinnitus, and more specifically, to assess the parameters associated with a long-term benefit in order to improve patient selection., Design: Subjects were 70 consecutive patients who came to our clinic from October 2016 to October 2018 for consultations on their tinnitus that persisted for one month or longer and were treated with an intra-articular injection of the temporomandibular joint with steroids. Patients charts, cervical spine radiographs and audiogram were reviewed retrospectively and data from these patients were recorded. An independent observer conducted a long-term follow-up assessment of the therapy by telephone interview., Results: Relief of tinnitus at seven-week follow-up was achieved in 20% of the patients treated with temporomandibular steroids. At 18 months, 50% of the patients successfully treated with temporomandibular steroids for tinnitus still experienced a benefit. Adverse events of the temporomandibular steroids reported at 7 weeks of follow-up were an increase of the intensity of their tinnitus in 11% of the patients and in 3% of the patient's side-effects of the steroids. Patients with temporomandibular disorders as cause of their tinnitus were identified by the presence of unilateral tinnitus in combination with cervical pain. In patients with unilateral tinnitus together with cervical pain, 53% of them had a reduction of their tinnitus at 7 weeks following treatment with temporomandibular steroids and for 40% of them the reduction of the tinnitus was 50% or more. An increase in the intensity of their tinnitus as adverse effect occurred in 7% of the patients in this group., Conclusions: Temporomandibular steroids can be a useful alternative for patients with tinnitus with a long term effect. However, patient selection is of vital importance, since patients with unilateral tinnitus and cervical pain respond the most to this therapy. Moreover, patient without these symptoms risk worsening the tinnitus. A prospective study should further evaluate these findings.

Introduction: Derangement of the temporomandibular joint complicates everyday life, due to the masticatory malfunction and the continuous pain sensation of the head and facial region. The therapy is multidisciplinary and varying. In case of the inefficiency of conservative therapy, minimally invasive intervention is needed with intraarticular injection., Aim: The aim of our study was to examine whether hyaluronic acid injection is more beneficial compared to corticosteroid in 37 joints. We also examined whether the efficacy of the therapy is influenced by hyaluronic acid molecular weight and the used protocol., Method: Wilkes stage, maximal mouth opening and the Visual Analogue Scale were determined pre-operatively and 6 months later. Corticosteroid application was performed once, hyaluronic acid was injected on a weekly bases 3 times in a row, by use of low (6-10 × 10 5 dalton) or high molecular weight (24-36 × 10 5 dalton) preparations., Results: The medical state of the patients treated with corticosteroid temporarily improved, but the symptoms returned. Due to hyaluronic acid treatment, significant improvement was revealed in all parameters (p wilkes <0.0001; p mouth-opening = 0.0002; p VAS <0.0001). There was no significant relapse (T = 2.05). The third administration of hyaluronic acid resulted in a significant improvement of the Visual Analogue Scale compared to the first and second injection (T 3.-1. = 20.37; T 3.-2. = 9.57)., Conclusions: Comparing the two agents we can state that hyaluronic acid was significantly more effective and its application for three times seems to be the most effective treatment decreasing the symptoms. The high molecular weight solution was more effective in increasing mouth opening. In contrast to hyaluronic acid, corticosteroid had no prolonged effect in higher Wilkes stages. Orv Hetil. 2018; 159(36): 1475-1482.

In the course of temporomandibular joint, dysfunctions very often occur to the excessive increase in tension of masticatory muscles, so the main aim of the treatment is reduction of this hypertension of muscles. For this reason, we use botulinum toxin type A, which is produced by Grampositive Clostridium bacteria. There are six serotypes of the toxin: A, B, C, D, E, F, and G. The botulinum toxin type A was first isolated in 1920s. Today, botulinum toxin type A is used increasingly more often as an efficient and patient-friendly therapy in neurology, ophthalmology, neurology, urology and laryngology. The aim of the article was to review the literature and description of the current knowledge concerned with mechanism of action of botulinum toxin type A, clinical applications and metabolic determinants of muscle contraction and the beneficial effect of this drug on the state of muscle tension., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Introduction: Temporomandibular disorders (TMDs) affect the masticatory muscles and the temporomandibular joints (TMJs). TMDs most often result from occlusal and/or muscular disorders and are then called primary or idiopathic TMDs. Less frequently, TMDs are related to local (trauma, infection) or general (rheumatoid arthritis) causes and are then called secondary TMDs. A little known iatrogenic cause of secondary TDM is the osteoarthritis that may be induced by intra-articular cortisone injections. We report one case of condylar lysis that occurred after one single intra-articular cortisone injection., Observation: A 62-years-old woman consulted for a long-lasting TMD on the left side manifesting itself through pain and noise. She benefited one year before from an intra-articular injection of cortisone by her rheumatologist for repeated closed lock of her left TMJ. Physical examination showed limited mouth opening with deviation on the left side. Lateral movements on the right side were impossible. The panoramic X-ray showed a condylar lysis on the left side that was on the CT scan. MRI additionally showed an anteriorly displaced and severely reshaped disc and an articular inflammation without intra-articular effusion., Discussion: TMJ osteoarthritis secondary to unique or repeated intra-articular steroid injections are little-known. They are clinically expressed as typical TMDs and characterized on X-rays by condylar lysis and inflammation. Intra-articular injections of steroids are not totally harmless and other treatments must be preferred., (Copyright © 2016. Published by Elsevier Masson SAS.)

Intra-articular injections of hyaluronic acid (HA) and corticosteroids have been extensively used in treating temporomandibular disorders. However, rapid clearance from the site of injection is a major concern that is commonly managed by frequent dosing, which is not without complications. This study aimed to determine the suitability of thermosensitive chitosan-based hydrogels for intra-articular controlled release of drugs in the rabbit temporomandibular joint (TMJ). A series of hydrogels were prepared using different chitosan (Ch) to β-glycerophosphate (β-GP) ratios. The gelation time, swelling ratio, the shape, and surface morphology of the prepared gels were investigated to select the formulation with optimum characteristics. The left TMJ in 13 adult male New Zealand white rabbits was injected with 0.2 mL of Chitosan/β-glycerophosphate/HA while the right TMJ was injected with 0.2 mL of control solution of HA. Hyaluronic acid concentrations in experimental and control groups were measured using Hyaluronan Quantikine Enzyme-Linked Immunosorbent Assay Kit. In vitro characterization showed that both the Ch:β-GP ratio and incorporation of HA had a significant effect on gelation time, degree of swelling, and surface morphology of the hydrogels. No morphological changes were observed in the joints in both groups. The mean concentration of HA in the experimental joints after 7 days (1339.79 ± 244.98 μg/g) was significantly higher than that in the control (474.52 ± 79.36 μg/g). In conclusion, the chitosan-based thermosensitive hydrogel can be considered as a promising controlled drug release system to the TMJ in a rabbit model that would potentially overcome many of the current limitations of intra-articular formulations.

Temporomandibular joint osteoarthritis (TMJ-OA) is characterized by progressive degradation of cartilage and changes in subchondral bone. It is also one of the most serious subgroups of temporomandibular disorders. Rebamipide is a gastroprotective agent that is currently used for the treatment of gastritis and gastric ulcers. It scavenges reactive oxygen radicals and has exhibited anti-inflammatory potential. The aim of this study was to investigate the impact of rebamipide both in vivo and in vitro on the development of cartilage degeneration and osteoclast activity in an experimental murine model of TMJ-OA, and to explore its mode of action. Oral administration of rebamipide (0.6 mg/kg and 6 mg/kg) was initiated 24 h after TMJ-OA was induced, and was maintained daily for four weeks. Rebamipide treatment was found to attenuate cartilage degeneration, to reduce the number of apoptotic cells, and to decrease the expression levels of matrix metalloproteinase-13 (MMP-13) and inducible nitric oxide synthase (iNOS) in TMJ-OA cartilage in a dose-dependent manner. Rebamipide also suppressed the activation of transcription factors (e.g., NF-κB, NFATc1) and mitogen-activated protein kinases (MAPK) by receptor activator of nuclear factor kappa-B ligand (RANKL) to inhibit the differentiation of osteoclastic precursors, and disrupted the formation of actin rings in mature osteoclasts. Together, these results demonstrate the inhibitory effects of rebamipide on cartilage degradation in experimentally induced TMJ-OA. Furthermore, suppression of oxidative damage, restoration of extracellular matrix homeostasis of articular chondrocytes, and reduced subchondral bone loss as a result of blocked osteoclast activation suggest that rebamipide is a potential therapeutic strategy for TMJ-OA.

Introduction: Juvenile idiopathic arthritis affecting the temporomandibular joint (TMJ) can cause severe disturbances of the mandibular development. Methotrexate (MTX) is often administered as a common used remission-inducing agent to treat this disease. The aim of this study was to investigate the effect of low dose MTX on the mandibular growth in arthritic rabbits., Subjects and Methods: Eighteen 10-week-old female New Zealand white rabbits were randomly assigned to three groups with six animals in each group. After being sensitized to ovalbumin (OA), the first and the second group received intra-articular injections with OA. The first group remained untreated, the second was treated by weekly injections of MTX. Cephalograms were taken from each animal at 10, 13, 16, 19, and 22 weeks of age and six mandibular distances measured., Results: All distances showed an increase between 10 and 20 per cent, whereas growth was more accentuated in the sagittal dimension. Significant differences in the overall growth could be observed between the arthritic and the control animals and less accentuated between the arthritic and the MTX animals. In contrast, existing differences between the groups were not significant during the intervals, but time had the greatest influence on mandibular growth., Conclusions: MTX seems to have a positive impact on growth in rabbits suffering from experimental arthritis of the TMJ., (© The Author 2014. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Juvenile idiopathic arthritis (JIA) often causes inflammation of the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. In this study, we evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ., Methods: Joint inflammation was initiated by injecting two doses of complete Freund's adjuvant (CFA) at 1-month intervals into the right TMJs of 24 growing Sprague-Dawley male rats (controls on left side). Four additional rats were not manipulated. With the second CFA injection, animals received (1) 5 mg of P-DEX intra-articularly (n = 9), (2) 15 mg of P-DEX into the tail vein (n = 7), or (3) nothing in addition to CFA (n = 8). The rats were killed 28 days later and measured by radiography for ramus height (condylar superior to gonion inferior [CsGoInf]), by micro-computed tomography for condylar width (CW) and bone volume/standardized condylar volume (BV/CV), and by histology for retrodiscal inflammatory cells. Inflammation targeting of systemic P-DEX was confirmed by IVIS infrared dye imaging. Inflammation and bone growth were compared between groups using analysis of variance and Pearson's correlations., Results: CFA caused a significant reduction in CsGoInf (p < 0.05), but neither route of P-DEX administration had an effect on CsGoInf or CW at CFA injection sites. BV/CV was significantly reduced in both inflamed and control condyles as a result of either steroid application (p < 0.05). The inflammatory infiltrate was overwhelmingly lymphocytic, comprising 16.4 ± 1.3 % of the field in CFA alone vs. <0.01 % lymphocytes in contralateral controls (p < 0.0001). Both P-DEX TMJ (10.1 ± 1.2 %) and systemic P-DEX (8.9 ± 1.7 %) reduced lymphocytes (p < 0.002). The total area of inflammatory infiltrate was significantly less in the systemic injection group than in the group that received CFA injections alone (2.6 ± 1.5 mm(2) vs. 8.0 ± 1.3 mm(2); p = 0.009), but not in the group that received intra-articular P-DEX (8.8 ± 1.2 mm(2))., Conclusions: High-dose systemic administration of inflammation-targeting P-DEX is more effective than an intra-articular injection in reducing TMJ inflammation, but both routes may affect TMJ bone density.

Objectives: To investigate whether low-level laser therapy (LLLT) alters the expression and activity of MMP-2 and MMP-9 in the trigeminal ganglion (TG) during different stages of temporomandibular joint (TMJ) inflammation in rats. It also evaluated whether LLLT modifies mechanical allodynia and orofacial hyperalgesia., Materials and Methods: Wistar rats (±250 g) were divided into groups that received saline (SAL) or complete Freund's adjuvant (CFA, 50 μl) in the TMJ, and that later underwent LLLT (20 J cm(-2) ) at their TMJ or not (groups SAL, SAL + LLLT, CFA, and CFA + LLLT). LLLT was applied on days 3, 5, 7, and 9 after SAL or CFA. Mechanical allodynia was evaluated on days 1, 3, 5, 7, and 10; orofacial hyperalgesia was assessed on day 10. Gelatin zymography and in situ zymography aided quantification of MMPs in the TG., Results: Low-level laser therapy abolished the reduction in the mechanical orofacial threshold and the increase in orofacial rubbing during the orofacial formalin test induced by CFA. LLLT also decreased the CFA-induced rise in the levels of MMP-9 and MMP-2 as well as the gelatinolytic activity in the TG., Conclusion: Low-level laser therapy could constitute an adjuvant therapy to treat temporomandibular disorders and prevent inflammation-induced alterations in the levels of MMP-2 and MMP-9 and in the gelatinolytic activity in TGs., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: We have previously demonstrated that blockade of β-adrenoreceptors (β-AR) located in the temporomandibular joint (TMJ) of rats suppresses formalin-induced TMJ nociceptive behaviour in both male and female rats, but female rats are more responsive. In this study, we investigated whether gonadal hormones modulate the responsiveness to local β-blocker-induced antinociception in the TMJ of rats., Methods: Co-administration of each of the selective β1 (atenolol), β2 (ICI 118.551) and β3 (SR59230A)-AR antagonists with equi-nociceptive concentrations of formalin in the TMJ of intact, gonadectomized and hormone-treated gonadectomized male and female rats., Results: Atenolol, ICI 118.551 and SR59230A significantly reduced formalin-induced TMJ nociception in a dose response fashion in all groups tested. However, a lower dose of each β-AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact and testosterone-treated gonadectomized male rats. In the female groups, a lower dose of β1 -AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact or gonadectomized rats treated with progesterone or a high dose of oestradiol; a lower dose of β2 -AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact and gonadectomized rats treated with low or high dose of oestradiol., Conclusion: Gonadal hormones may reduce the responsiveness to local β-blocker-induced antinociception in the TMJ of male and female rats. However, their effect depends upon their plasma level, the subtype of β-AR and the dose of β-blockers used., (© 2014 European Pain Federation - EFIC®)

High molecular weight hyaluronic acid (HMWHA) has been used to treat temporomandibular joint (TMJ) disorders, but controversial results have been described. This study aimed to characterize the morphological and biochemical actions of HMWHA on induced arthritis of the TMJ. Twenty-four male Wistar rats were used, and arthritis of the TMJ was induced through an intra-articular injection of Complete Freund's Adjuvant (CFA) (50 μl). One week after arthritis induction, the animals were treated with HMWHA (once per week for three weeks). Histological analyses were performed using sections stained with hematoxylin-eosin, toluidine blue and Picrosirius. Were also performed histomorphometric analysis and birefringence of collagenous fibers (polarization microscopy). Biochemical analyses of TMJ tissues were carried out through measurements of sulfated glycosaminoglycans and zymography for evaluation of metalloproteinase-2 and -9 (MMP-2 and -9). Data were analyzed using paired t-test and unpaired t-test, with a 5% significance level. HMWHA reduced histologic changes and thickness of the articular disc, led to a greater arrangement of collagenous fibers, lower concentration of sulfated glycosaminoglycans and lower activity in all isoforms of MMP-2 and -9 in TMJs with induced arthritis. These findings suggest that HMWHA may exert a protective effect on the TMJ., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Objective: Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role for female hormones in the disease process. However, little is known about the role of estrogen receptor (ER) signaling in regulating mandibular condylar cartilage growth. Therefore, the goal of this study was to examine the effects of altered estrogen levels on the mandibular condylar cartilage in wild type (WT) and ER beta Knockout (KO) mice., Materials and Methods: 21-day-old female WT (n = 37) and ER beta KO mice (n = 36) were either sham operated or ovariectomized, and treated with either placebo or estradiol. The mandibular condylar cartilage was evaluated by histomorphometry, proliferation was analyzed by double ethynyl-2'-deoxyuridine/bromodeoxyuridine (EdU/BrdU) labeling, and assays on gene and protein expression of chondrocyte maturation markers were performed., Results: In WT mice, ovariectomy caused a significant increase in mandibular condylar cartilage cell numbers, a significant increase in Sox9 expression and a significant increase in proliferation compared with sham operated WT mice. In contrast, ovariectomy did not cause any of these effects in the ER beta KO mice. Estrogen replacement treatment in ovariectomized WT mice caused a significant decrease in ER alpha expression and a significant increase in Sost expression compared with ovariectomized mice treated with placebo. Estrogen replacement treatment in ovariectomized ER beta KO mice caused a significant increase in Col2 expression, no change in ER alpha expression, and a significant increase in Sost expression., Conclusion: Estrogen via ER beta inhibits proliferation and ER alpha expression while estrogen independent of ER beta induces Col2 and Sost expression., (Copyright © 2014 China University of Geosciences (Beijing) and Peking University. Published by Elsevier Ltd. All rights reserved.)

Over the last decade the use of hyaluronic acid has become increasingly important in treatment of degenerative disorders of the temporomandibular joint. Urgency is caused by numerous studies in biology and pharmacology on structure and function of hyaluronic acid and its influence on the processes of repair damaged bone and articular cartilage restoration, as well as the positive long-term results of treatment in this group of patients.

Temporomandibular joint osteoarthritis (TMJOA) is clinically characterized by female preponderance, with a female-to-male ratio of more than 2:1; however, the underlying mechanism remains obscure. We examined the effects of estrogen on TMJOA induced by monosodium iodoacetate. Female rats were randomly and equally divided into 5 groups: control, sham-ovariectomized, and ovariectomized rats treated, respectively, with 17β-estradiol (E2) at doses of 0 µg, 20 µg, and 80 µg/day until the end of the experiment. After induction of TMJOA, TMJs were evaluated by histopathology and microCT, and the expression of Fas, FasL, caspase 3, and caspase 8 was evaluated by real-time polymerase chain-reaction or immunohistochemistry. Another 5 groups of female rats were used to evaluate the effect of estrogen receptor antagonist ICI 182780 on E2 effects on TMJOA, when injected intraperitoneally into the control, sham-ovariectomized, and 80-µg-E2-treated groups. We found that E2 potentiated cartilage degradation and subchondral bone erosion in iodoacetate-induced TMJOA. E2 also potentiated mRNA expression of Fas, FasL, caspase 3, and caspase 8 in the condylar cartilage. Moreover, the estrogen receptor antagonist partially blocked E2 effects on TMJOA. These findings suggest that E2 could aggravate TMJOA, which may be an important mechanism underlying the sexual dimorphism of TMJOA.

Purpose: The purpose of this study was to evaluate the safety and efficacy of intra-articular corticosteroid injections (IACIs) of the temporomandibular joint (TMJ) in children with juvenile idiopathic arthritis (JIA) when administered by an oral and maxillofacial surgeon without imaging guidance., Materials and Methods: This was a retrospective study of children with JIA, seen at a single center, who were selected based on having received IACIs of the TMJ. All subjects received the intervention, which consisted of referral to a single oral and maxillofacial surgeon for TMJ IACI with 5 to 10 mg triamcinolone hexacetonide, under general anesthesia. Primary outcomes assessed in all subjects were the safety of the procedure and efficacy as determined by the change in maximal incisal opening (MIO). In addition, a subset of 31 subjects underwent repeat magnetic resonance imaging of the TMJ, permitting analysis of the change in the acute and chronic findings of arthritis in those patients., Results: Sixty-three patients (68% female) received 137 IACIs. The mean age for diagnosis of JIA was 8.5 years, and the mean age at presentation for TMJ injections was 10 years. The injections were well tolerated: only 1 patient developed the steroid complication of hypopigmentation, and none developed degeneration or ankylosis. In terms of efficacy, the mean MIO increased from 40.8 ± 0.93 to 43.5 ± 0.90 mm (P = .001); in addition, changing the unit of analysis to individual joints, in patients who underwent repeat magnetic resonance imaging examination, 51% of TMJs showed magnetic resonance imaging evidence of improvement of arthritic changes, of whom 18% had complete resolution of TMJ arthritis., Conclusions: The results indicate that IACI of the TMJ can be safely performed by experienced oral and maxillofacial surgeons without a requirement for computed tomographic guidance. In addition, these results show that IACI may be effective in the management of TMJ arthritis, although further studies are required., (Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Temporomandibular joint (TMJ) involvement is common in juvenile idiopathic arthritis (JIA). Dexamethasone iontophoresis (DIP) uses low-grade electric currents for transdermal dexamethasone delivery into deeper anatomic structures. The purpose of this study was to assess the safety and effectiveness of DIP for the treatment of TMJ involvement in JIA, and to delineate variables that are associated with improvement after DIP., Methods: Medical records of all JIA patients who underwent DIP for TMJ involvement at a larger tertiary pediatric rheumatology center from 1997-2011 were reviewed. DIP was performed using a standard protocol. The effectiveness of DIP was assessed by comparing the maximal interincisor opening (MIO(TMJ) ) and the maximal lateral excursion (MLE(TMJ) ) before and after treatment., Results: Twenty-eight patients (ages 2-21 years) who received an average of 8 DIP treatment sessions per involved TMJ were included in the analysis. Statistically significant improvement in the median MIO(TMJ) (P < 0.0001) was observed in 68%. The median MLE(TMJ) (P = 0.03) improved in 69%, and resolution of TMJ pain occurred in 73% of the patients who had TMJ pain at baseline. Side effects of DIP were transient site erythema (86%), skin blister (4%), and metallic taste (4%). Improvement in TMJ range of motion from DIP is associated with lower MIO(TMJ) , lower MLE(TMJ) , and absence of TMJ crepitus at baseline., Conclusion: In this pilot study, DIP appeared to be an effective and safe initial treatment of TMJ involvement in JIA, especially among patients with decreased TMJ measurements. Prospective controlled studies are needed., (Copyright © 2011 by the American College of Rheumatology.)

Endogenous microparticles (MPs) were systematically profiled during the time course of self-limited inflammation. Precursors for specialized proresolving lipid mediators were identified in MPs from inflammatory exudates using liquid chromatography tandem mass spectrometry-based metabolomics. Hence, we postulated that formation of anti-inflammatory and proresolving lipid mediators could underlie beneficial effects attributed to MPs and that this process could serve as a basis for biomimicry. Using human neutrophil-derived MPs, we constructed novel nanoparticles (NPs) containing aspirin-triggered resolvin D1 or a lipoxin A(4) analog. Enriched NPs dramatically reduced polymorphonuclear cell influx in murine peritonitis, shortened resolution intervals, and exhibited proresolving actions accelerating keratinocyte healing. The enriched NPs protected against inflammation in the temporomandibular joint. These findings indicate that humanized NPs, termed nano-proresolving medicines, are mimetics of endogenous resolving mechanisms, possess potent beneficial bioactions, can reduce nanotoxicity, and offer new therapeutic approaches.

Aim: The aim of this study was to evaluate, by light microscopy, the effects of laser phototherapy (LPT) at 780 nm or a combination of 660 and 790 nm, on the inflammatory process of the rat temporomandibular joint (TMJ) induced by carrageen., Background: Temporomandibular disorders (TMDs) are frequent in the population and generally present an inflammatory component. Previous studies have evidenced positive effects of laser phototherapy on TMDs. However, its mechanism of action on the inflammation of the TMJ is not known yet., Materials and Methods: Eighty-five Wistar rats were divided into 9 groups: G1, Saline; G2, Saline + LPT IR; G3, Saline + LPT IR + R; G4, Carrageenan; G5, Carrageenan + LPT IR; G6, Carrageenan + LPT IR + R; G7, previous LPT + Carrageenan; G8, previous LPT + carrageenan + LPT IR; and G9, previous LPT + carrageenan + LPT IR + R, and then subdivided in subgroups of 3 and 7 days. After animal death, specimens were taken, routinely cut and stained with HE, Sirius Red, and Toluidine Blue. Descriptive analysis of components of the TMJ was done. The synovial cell layers were counted., Results: Injection of saline did not produced inflammatory reaction and the irradiated groups did not present differences compared to nonirradiated ones. After carrageenan injection, intense inflammatory infiltration and synovial cell layers proliferation were observed. The infrared irradiated group presented less inflammation and less synovial cell layers number compared to other groups. Previous laser irradiation did not improve the results., Conclusion: It was concluded that the LPT presented positive effects on inflammatory infiltration reduction and accelerated the inflammation process, mainly with IR laser irradiation. The number of synovial cell layers was reduced on irradiated group.

The temporomandibular joint (TMJ) formalin test was used to evaluate the effects of acute restraint stress on the nociceptive behavioral responses of female rats during proestrus and estrus phases of the estrous cycle. Rats were subjected to one session of restraint stress (15, 30 min or 1 h). They were then either immediately killed to allow the collection of blood for hormonal radioimmunoassay determinations or subjected to TMJ formalin test to evaluate nociception. All stress protocols significantly raised the plasma concentrations of corticosterone. The performance of rats subjected to 15 and 30 min of restraint stress was similar to that of control rats, whereas rats that were stressed for 1 h showed a decrease in nociceptive responses, during both proestrus and estrus phases. The stress-induced analgesia (SIA) was greater in the proestrus phase. To evaluate the role of kappa-opioid receptors, the selective receptor kappa-opioid antagonist nor-binaltorphimine (nor-BNI; 200 microg or saline) was injected into the TMJ 24 h prior to the 1 h stress period and the TMJ formalin test. The local administration of nor-BNI partially reversed the SIA during the proestrus phase. These findings suggest that (1) acute stress for 1 h can produce analgesia both during proestrus and estrus phases; this effect is greater during the proestrus phase and (2) kappa-opioid receptor activation is involved in the SIA observed in the proestrus phase.

Objectives: The aim of this study was to compare the effectiveness of using Ping On ointment and using petroleum jelly in the treatment of temporomandibular joint (TMJ) and masticatory muscle pain, in order to establish the true efficacy of Ping On ointment., Methods: In this randomized, double-blinded, placebo-controlled trial, 55 subjects with TMJ and/or masticatory pain (Group I patients according to the Research Diagnostic Criteria for Temporomandibular Disorder (RDC/TMD) received Ping On ointment for 4 weeks, or placebo for 4 weeks. Subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analogue scale and maximal comfortable mandibular opening, at baseline and again after 4 weeks of treatment., Results: Ping On ointment significantly reduced the symptoms of painful TMJs and/or masticatory muscles. Maximal comfortable mandibular opening also improved in the Ping On ointment group compared with the placebo, but was not clinically significant., Conclusions: This preliminary study suggests that topical application of Ping On ointment may be considered for further investigation as a potential first-line treatment modality, before prescribing analgesics, for the management of TMDs. It is topically applied, safe, reversible, and effective in managing TMDs and masticatory muscle pain.

Objective: This study aimed to examine the effect of injection of transforming growth factor beta (TGF-beta) on articular cartilage in osteoarthritic temporomandibular joint (TMJ)., Study Design: Disc perforation was performed bilaterally in 24 rabbits to induce osteoarthritis (OA). The right joint was injected with TGF-beta as experimental groups, and the left joint with physiologic saline as control. Animals were killed at different intervals. Histology and reverse transcriptase polymerase chain reaction was performed for comparison., Results: All joints showed OA-like changes, but the degree in the experimental was significantly less severe than in the control. At 12 weeks a significantly greater expression of aggrecan and collagen type II was found in the experimental compared with the control joints. However, no difference in either anabolic or catabolic genes was found between the two groups at 24 weeks., Conclusions: Transforming growth factor beta may have a potential benefit in protecting articular cartilage during the development of TMJ OA.

Recent studies have hypothesized that peripheral glutamate receptors could be implicated in deep craniofacial pain conditions. In this study 18 temporomandibular joint (TMJ) arthralgia patients received intra-articular injections of the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, or normal saline to study in a cross-over, double-blinded, placebo-controlled manner the effect on TMJ pain and somatosensory function. Spontaneous pain and pain on jaw function was scored by patients on 0-10 cm visual analogue scale (VAS) for up to 24h. Quantitative sensory tests (QST): tactile, pin-prick, pressure pain threshold and pressure pain tolerance were used for assessment of somatosensory function at baseline and up to 15 min after injections. There were no significant effects of intra-articular ketamine over time on spontaneous VAS pain measures (ANOVA: P=0.532), pain on jaw opening (ANOVA: P=0.384), or any of the somatosensory measures (ANOVA: P>0.188). The poor effect of ketamine could be due to involvement of non-NMDA receptors in the pain mechanism and/or ongoing pain and central sensitization independent of peripheral nociceptive input. In conclusion, there appears to be no rationale to use intra-articular ketamine injections in TMJ arthralgia patients, and peripheral NMDA receptors may play a minor role in the pathophysiology of this disorder.

Unlabelled: The aim of this study was to investigate the influence of sex and ovarian hormones on formalin- and glutamate-induced temporomandibular joint (TMJ) nociception in rats. The influence of sex and ovarian hormones on the nociceptive behavior induced by formalin or glutamate was virtually the same. The nociceptive behavior of males was similar to that of females in the proestrus phase of the estrous cycle but was significantly lower than that in the diestrus phase. Since the serum level of estradiol but not of progesterone was significantly higher in the proestrus than in the diestrus phase, these data suggest that females with lower endogenous serum level of estradiol have an exacerbation of TMJ nociception. The nociceptive behavior of ovariectomized rats was similar to that of diestrus females and significantly greater than that of proestrus females. Although the administration of estradiol or progesterone in ovariectomized females significantly reduced TMJ nociception, the combination of both hormones did not increase the antinociceptive effect induced by each of them. These findings suggest that estradiol and progesterone decrease TMJ nociception in an independent way., Perspective: We report that ovarian hormones have an antinociceptive effect on the TMJ formalin and glutamate nociceptive behavior models. Therefore, the greater prevalence and severity of TMJ pain in women of reproductive age may be a consequence of hormonal fluctuation during the reproductive cycle, in that during low endogenous estradiol serum level TMJ pain sensitivity is increased, enhancing the risk of females experiencing TMJ pain.

Purpose: The purpose of this study was to evaluate the effect of estrogen on the synthesis of cytokines of the temporomandibular joint cells., Methods: Mandibular condyles of 10 mice were resected. Twenty of these condylar cartilages were removed and placed in organ culture for 24 hours with media containing different concentrations of 17beta-estradiol. The chondroblasts from the mandibular condyles of 3 mice were cultured with different concentrations of 17beta-estradiol the same as above. Cytokine concentrations were measured by ELISA., Results: The expression and concentration of IL-1 beta, IL-6, and IL-8 were increased with increasing concentration of 17beta-estradiol. The expression and concentration of IL-4 and IL-10 were not different from the control and experimental group., Conclusions: These findings suggest that estrogen has the potential to cause temporomandibular joint disease with induction of the proinflammatory cytokines, IL-1 beta, IL-6, and IL-8.

Septic arthritis of the temporomandibular joint (TMJ) is rare, and is almost exclusively confined to adults; we know of only four cases previously described in children. We present a 6-year-old girl who had septic arthritis of the temporomandibular joint with no obvious cause. We stress the need for prompt diagnosis and intervention to prevent serious consequences.

Leukotriene B4 (LTB4) mediates different inflammatory events such as neutrophil migration and pain. The present study addressed the mechanisms of LTB4-mediated joint inflammation-induced hypernociception. It was observed that zymosan-induced articular hypernociception and neutrophil migration were reduced dose-dependently by the pretreatment with MK886 (1-9 mg/kg; LT synthesis inhibitor) as well as in 5-lypoxygenase-deficient mice (5LO(-/-)) or by the selective antagonist of the LTB(4) receptor (CP105696; 3 mg/kg). Histological analysis showed reduced zymosan-induced articular inflammatory damage in 5LO(-/-) mice. The hypernociceptive role of LTB4 was confirmed further by the demonstration that joint injection of LTB4 induces a dose (8.3, 25, and 75 ng)-dependent articular hypernociception. Furthermore, zymosan induced an increase in joint LTB4 production. Investigating the mechanism underlying LTB4 mediation of zymosan-induced hypernociception, LTB4-induced hypernociception was reduced by indomethacin (5 mg/kg), MK886 (3 mg/kg), celecoxib (10 mg/kg), antineutrophil antibody (100 mug, two doses), and fucoidan (20 mg/kg) treatments as well as in 5LO(-/-) mice. The production of LTB4 induced by zymosan in the joint was reduced by the pretreatment with fucoidan or antineutrophil antibody as well as the production of PGE2 induced by LTB4. Therefore, besides reinforcing the role of endogenous LTB4 as an important mediator of inflamed joint hypernociception, these results also suggested that the mechanism of LTB4-induced articular hypernociception depends on prostanoid and neutrophil recruitment. Furthermore, the results also demonstrated clearly that LTB4-induced hypernociception depends on the additional release of endogenous LTs. Concluding, targeting LTB4 synthesis/action might constitute useful therapeutic approaches to inhibit articular inflammatory hypernociception.

A considerable amount of evidence suggests that temporomandibular joint (TMJ) pain associated with temporomandibular disorder results, at least in part, from an inflammatory episode. Although histamine can cause pain, it is not clear whether this mediator induces nociception in the TMJ. In this study, we investigated the contribution of endogenous histamine to formalin-induced nociception in the TMJ of rats. We also investigated whether the administration of histamine induces nociception in the TMJ and, if so, whether this effect is mediated by an indirect action on primary afferent nociceptors. Local administration of the H1-receptor antagonist pyrilamine prevented formalin-induced nociception in the TMJ in a dose-dependent manner. Local administration of histamine (250 microg) in the TMJ induced nociceptive behavior that was inhibited by co-administration of the lidocaine N-ethyl bromide quaternary salt QX-314 (2%) or the selective H1-receptor antagonist pyrilamine (400 microg). Nociception induced by histamine was also inhibited by pre-treatment with sodium cromoglycate (800 microg) and by co-administration of the 5-HT(3) receptor antagonist tropisetron (400 mug), while pyrilamine (400 mug) did not inhibit nociception induced by 5-hydroxytryptamine (5-HT, 250 microg) in the TMJ. Furthermore, histamine, in a dose that did not induce nociception by itself, strongly enhanced 5-HT-induced nociception. Finally, the administration of a sub-threshold dose of 5-HT (100 microg), but not of histamine (100 microg), elicited nociception in the TMJ previously challenged with the inflammatory agent carrageenan (100 microg). In conclusion, these data suggest that histamine induces TMJ nociception by an indirect mechanism involving endogenous release of 5-HT and activation of 5-HT(3) receptors on sensory afferents. It is proposed that histamine activates the H1 receptor to induce the release of 5-HT which depolarizes the nociceptor by activating 5-HT(3) receptor.

Objective: To assess the effects of computed tomography (CT)-guided injection of corticosteroid into the temporomandibular joint (TMJ) in children with juvenile idiopathic arthritis (JIA) and clinical and magnetic resonance imaging (MRI) evidence of TMJ inflammation., Methods: Twenty-three children ages 4-16 years with JIA and MRI evidence of TMJ inflammation received CT-guided TMJ injections of corticosteroid (triamcinolone acetonide [n = 16] or triamcinolone hexacetonide [n = 7]). Jaw pain or dysfunction and maximal incisal opening (MIO) distance were assessed before and after injection. Fourteen patients had followup MRI studies of the TMJ 6-12 months after injection., Results: Of the 13 patients with symptoms of jaw pain prior to corticosteroid treatment, 10 (77%) had complete resolution of pain (P < 0.05). Prior to corticosteroid injection, MIO in all 23 patients was below age-matched normal values. After injection, the MIO was improved by at least 0.5 cm in 10 patients (43%) (P = 0.0017). Patients under 6 years of age at the time of injection showed the best response, with a postinjection MIO similar to that in age-matched controls (P = 0.2267). There was involvement of 23 TMJs in the 14 patients who had followup MRI studies; resolution of effusions was observed in 11 (48%) of the TMJs. Other than short-term facial swelling in 2 patients, there were no side effects., Conclusion: The majority of children with symptomatic TMJ arthritis improved after intraarticular corticosteroid injection. Approximately half the patients experienced significant improvement in MIO and TMJ effusion. These data suggest that corticosteroid injection may be a useful procedure for the prevention and treatment of morbidities associated with TMJ arthritis in JIA.

Objective: To evaluate influence of mitomycin C on fibrosis in temporomandibular joints of rabbits with mandibular traction., Study Design: Twenty rabbits (8 control, 12 mitomycin C group) were included. Titanium screws were placed in the anterior edge of the right masseter tuberosity and the posterior part of the right zygoma. Elastic bands were placed between 2 screws to initiate posterio-superior displacement of the mandible to the right. Animals in the control group (CG) received intraarticular NaCl (0.9%) on the nondrawing (left) side, and animals in the study group (SG) received mitomycin C weekly (0.4 mg/mL) for 6 weeks. Rabbits were decapitated, temporomandibular joints were removed, and histopathological investigation was performed., Results: Microscopically, 4 of 6 rabbits in the CG had fibrosis in the temporomandibular joint, whereas only 1 of 11 rabbits in the SG had fibrosis (P < 0.05)., Conclusion: Application of mitomycin C to the temporomandibular joint of rabbits significantly reduces formation of intraarticular fibrous adhesions., Significance: This is the first study in the literature investigating the use of mitomycin C in the joints., Ebm Rating: B-2.

Aims: To evaluate how the frictional coefficient of the porcine temporomandibular joint (TMJ) is affected by an impairment of the synovial lubrication produced by an experimental abrasion of the articular cartilage and the application of hyaluronic acid (HA) with different molecular weights to the abraded cartilage surfaces., Methods: Erosion of the articular cartilage was produced by scouring it with sandpaper. Impairment and restoration of synovial lubrication were modeled by washing the joint space with phosphate-buffered saline (PBS) and by the application of HA with different molecular weights. After measuring the frictional coefficients in the intact TMJs (n = 10), the effects of washing with PBS, sandpaper scouring, and the application of HA were subsequently examined., Results: The mean frictional coefficient in the intact joint was 0.0154 (SD 0.0043). After PBS washing and sandpaper scouring, it increased significantly to 0.0235 (SD 0.0052) and 0.0520 (SD 0.0088), respectively. Subsequent application of HA resulted in a significant decrease (43% to 56%) of the frictional coefficient. Observations by scanning electron microscopy showed that after sandpaper scouring, the superficial cartilage layer was disrupted and inner layer was exposed, creating an irregular surface., Conclusion: Joint friction may increase by approximately 350% following an experimental scouring of the cartilage surface and impairment of synovial lubrication. Lubrication by means of HA decreased joint friction by approximately 50%.

This article investigates the anti-inflammatory effects of erythromycin (EM) on aseptic inflammation of temporomandibular joint (TMJ) space using by Tc-99 m HIG scintigraphy and histopathology. In this experimental study, 33 adult male New Zealand White rabbits were divided into three groups. The animals in the first group were treated with EM 25 mg kg(-1); the animals in the second group were treated with methylprednisolone (MP) 2 mg kg(-1) and the animals in the third group were given saline solution (control group). Each drug was given by intraperitoneal injection twice a day for 7 days. Two hours after the last injection, carrageenan was injected into right TMJ of rabbits for aseptic inflammation. After carrageenan injection, each rabbit was given an intravenous injection of 111 Mbq (3 mCi) Tc-99 m human HIG, and scanning was performed 4 h later. Later, all animals were killed and TMJ and periarticular tissues were resected. Histopathologically, the distance between synovial surface epithelium (SSE) and muscle layer (ML) in each section was measured by using SAMBA 200 Cell image processor with software. Scintigraphically, when lesion activity/adjacent region activity (L/N) was evaluated there was a significant difference between the control group and the other two groups (P < 0.05 for EM and MP). However, no significant difference was found between the EM and MP groups. Histopathologically, the mean distance between SSE and ML in the sections was found longer in the control group (78.6 +/- 10.7 microm) than in the EM (44.38 +/- 18.26 microm) and MP (44.05. +/- 18.25 microm) groups. We think that administration of EM, which is a well-known macrolid antibiotic, might be very effective in the treatment of aseptic inflammation of TMJ space. Because corticosteroid administration has many side effects, EM may be a preferable drug in the treatment of inflammation of TMJ.

The aim of this study was to evaluate the effects of the injection of two phlogistic agents, carrageenan and formalin, in the rat TMJ, and the inflammatory process induced by these substances. In this study, a total of 45 adult rats were distributed in two experimental groups and a control group. The animals were sacrificed after three hours, 24 hours, three days, seven days, and 15 days after a single injection of each substance. Histological data initially demonstrated an inflammatory process represented by acute infiltration, which later became mixed, and finally chronic in both experimental groups. Hyperplasia of the synovial membrane was observed after three days, being intense at seven days, and present after 15 days only in the formalin group. Local saline injection in the control group caused no inflammatory reaction. It was concluded that a single local injection of carrageenan or formalin was enough to induce inflammatory reaction in the TMJ and periarticular soft tissues, and that the resulting processes were similar, but more persistent in the formalin group.

Aims: To study the neurogenic effects of a cyclooxygenase-2 (COX-2) inhibitor, rofecoxib, in an animal model of persistent inflammation., Methods: Arthritis was induced within the temporomandibular joint (TMJ) by placing complete Freund's adjuvant (CFA) within the superior joint space of the TMJ in adult male rats. The CFA animals were divided into 2 groups, with 1 group given the COX-2 inhibitor, rofecoxib, on days 21 through 28. Tissues were taken from experimental and control animals 4 weeks post-injection and analyzed by radioimmunoassay. The inflammatory-related neuropeptide, immunoreactive calcitonin gene-related peptide (CGRPi), was assayed from both the TMJ tissues and the trigeminal brain stem subnucleus caudalis., Results: CGRPi content was significantly increased in TMJ tissues within the untreated CFA group (72%) and was found to be effectively no different between the CFA/COX-2 group and controls. Trigeminal brain stem subnucleus caudalis CGRPi levels were not different between the groups., Conclusion: These results suggest that use of an inhibitor selective for the inducible form of cyclooxygenase enzyme, COX-2, may significantly attenuate the neurogenic component in an inflammatory TMJ animal model.

Botulinum toxin (BTX) has been used successfully to treat various movement disorders, and is increasingly used for many other medical conditions. Sialorrhoea is a disabling symptom in many neurological patients including those with Parkinson's disease, stroke and amyotrophic lateral sclerosis (ALS). BTX has recently been shown to be effective for treating sialorrhoea. We report an ALS patient who developed recurrent jaw dislocation following BTX treatment for sialorrhoea to highlight the observation that intraparotid BTX may be complicated by jaw dislocations in some at-risk ALS patients. Clinicians using BTX to treat sialorrhoea in ALS need to be aware of this potentially serious complication.

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.

To study the interaction between human recombinant interleukin-1 alpha and the nervous system, substance P-, neurokinin A-, calcitonin gene-related peptide-, and neuropeptide Y-like immunoreactivity in the cerebrospinal fluid, plasma, and temporomandibular joint (TMJ) perfusates of rats during acute experimental monarthritis were examined. The right TMJs of the experimental rats were injected with 0.01 mL of human recombinant interleukin-1 alpha. The right TMJs of control rats were injected with 0.01 mL of saline. Cerebrospinal fluid, plasma, and perfusates from the right TMJs were obtained at 2, 6, and 24 hours following injection, and neuropeptide-like immunoreactivity was analyzed by specific radioimmunoassays. Values of neuropeptide-like immunoreactivity for the experimental rats were compared with those of the control rats. In the experimental group, substance P-, neurokinin A-, and calcitonin gene-related peptide-like immunoreactivities were increased in cerebrospinal fluid compared to those of the control group. In plasma, no changes in neuropeptide-like immunoreactivities rose significantly in the TMJ perfusates. Most pronounced changes in neuropeptide Y-like immunoreactivity occurred intra-articularly in the TMJ perfusates. The results indicate that the contribution of the nervous system to human recombinant interleukin-1 alpha-induced monarthritis is most pronounced in the affected joint.

This is a study of neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)- like immunoreactivity(-LI) in the cerebrospinal fluid (CSF), plasma and perfusates (PF) from the temporomandibular joints (TMJs) of the rat during acute inflammation. Substance P (10(-5) M, 0.01 ml) was injected into the right TMJ of the rat. The TMJs of the control rats, were injected with 0.01 ml saline. CSF, plasma and PF from TMJs were taken at 2, 6 and 24 hrs following injection. The neuropeptide-LI level was analysed by specific radioimmunoassays and compared with control values. Unilateral injection of SP into the rat TMJ resulted in a general increase in the concentration of NKA-, CGRP- and NPY-LI in the TMJ PF at 2, 6 and 24 hrs following injection. In the CSF NKA- and CGRP-LI was increased leaving the NPY-LI unaffected. In general no changes in peptide concentrations were seen in plasma. The results indicate that SP directly or indirectly induces a local release of peptides through an action at sensory and sympathetic neurons.

The surgical treatment of internal derangements of the temporomandibular joint (TMJ) often involves disc removal. Alloplastic interpositional implants for disc replacement have been widely used to avoid the development of osteoarthritic changes in the TMJ. This study reports the in vivo wear characteristics of Proplast-Teflon (Vitek Inc, Houston, TX) interpositional implants (PTIPI) in 12 patients who had their implants for 13 to 71 (mean 54.6 +/- 5.8 SEM) months. In all cases, changes in the condyle and fossa were found resulting from resorption and replacement of the articulating bone by granulomatous tissue. All implants showed significant signs of wear, such as thinning, cracks, and tears, and overt perforations were seen in five cases. Scanning electron microscopy (SEM) combined with energy-dispersive x-ray microanalysis (EDAX) showed numerous microfragments of the PTIPI in the peri-implant soft tissues. Microfragments were demonstrated by their aluminum content. In addition to the inflammatory foreign-body reaction, it is suggested that there also were toxic and hypersensitivity reactions to aluminum involved in the pathogenesis of the bone destruction.