Inflammatory and degenerative effects of induced osteoarthritis/rheumatoid arthritis models on temporomandibular joint of rats.

OBJECTIVE: The present study compared three models of induction of osteoarthritis (OA) and rheumatoid arthritis (RA) in the temporomandibular joint (TMJ) of rats. DESIGN: The induction method was by injection of complete Freund's adjuvant (CFA) + type II bovine collagen (CII). Twenty-four adult male rats were divided into four groups (n = 6): G1: Sham, 50 µL of 0.9% sodium chloride at the base of the tail and in each TMJ; G2: OA, 50 µL CFA+CII in each TMJ; G3: RA+OA, 100 µL of CFA+CII at the base of the tail and 50 µL CFA+CII in each TMJ; G4: RA, 100 µL of CFA+CII at the base of the tail. All injections were repeated 5 days later. Twenty-three days after the first injection, the animals were sacrificed and the TMJs were submitted to histomorphometric analysis and measurement of cytokines. The Kruskal-Wallis and Dunn tests were used (alpha=0.05). RESULTS: The total thickness of the condylar cartilage increased in G2 in relation to the other groups, G3 and G4 reduced in relation to G1; and G2 and G4 reduced in relation to G2 and G3. The levels of IL-1ß, IL-6 and TNF-α increased in the three induction models compared to G1. The level of IL-10 increased in G2 compared to the other groups and reduced in G3 and G4 compared to G1. CONCLUSION: CFA+CII induced inflammation and degeneration compatible with RA (advanced chronic stage) when injected in the tail, and compatible with OA (acute stage or early disease) when injected only in the TMJ.

[Mechanism of microRNA-100-5p on mammalian target of rapamycin in temporomandibular arthritis].

PURPOSE: To investigate the mechanism of microRNA-100-5p (miR-100-5p) on mammalian target (mTOR) of rapamycin in temporomandibular arthritis. METHODS: Sixty SD rats were randomly divided into group A, group B, group C, group D, and group E, with 12 rats in each group. Rat models of temporomandibular arthritis were prepared by injecting sodium iodoacetate solution into the bilateral spaces of temporomandibular joint. After establishment, group C was injected pcDNA3.1-miR-100-5p recombinant plasmid, group D was injected mTOR inhibitor rapamycin, group E was injected with pcDNA3.1-miR-100-5p recombinant plasmid and rapamycin, and group A was injected same amount of normal saline in the same way. Various indexes were observed in each group, including morphological changes of temporomandibular joint tissues, matrix metalloproteinase-3 (MMP-3), MMP-1, MMP-13, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), miR-100-5p, mTOR expression. The data were processed using SPSS 22.0 software package. RESULTS: In group B, the structure of temporomandibular joint was fuzzy, with synovial hyperplasia, vascular dilatation, clustered cells and a large amount of inflammatory infiltration. Histopathological changes of temporomandibular joint in each interventional group were improved to different degrees compared with group B, among which group E showed the most obvious improvement. The levels of MMP-3, MMP-1, MMP-13, IL-6, IL-1ß and TNF-α in group B were significantly higher than those in group A(P＜0.05). The levels of MMP-3, MMP-1, MMP-13, IL-6, IL-1ß and TNF-α in group C, group D and group E were significantly lower than those in group B(P＜0.05). The levels of MMP-3, MMP-1, MMP-13, IL-6, IL-1ß and TNF-α in group D were not significantly different from those in group C (P＜0.05). The levels of MMP-3, MMP-1, MMP-13, IL-6, IL-1ß and TNF-α in group E were significantly lower than those in group D (P＜0.05). The expression level of miR-100-5p in group E was significantly higher than that in group B (P＜0.05). The expression level of mTOR protein in group E was significantly lower than that in group B (P＜0.05). CONCLUSIONS: MicroRNA-100-5p may alleviate temporomandibular arthritis by down-regulating the expression of mTOR.

Bilateral temporomandibular joint dislocations post-bronchoscopy in a case of paclitaxel-induced pneumonitis.

This case report presents the unusual complication of bilateral temporomandibular joint dislocation following bronchoscopy, highlighting the importance of recognising it as a differential diagnosis in patients having jaw symptoms. The delayed diagnosis in this case resulted in multiple unsuccessful reduction attempts under sedation, which added to the distress of the patient. Notably, the procedure yielded a rare diagnosis for the patient that intrinsically changed the management of her breast cancer.

P2X7-induced nociception in the temporomandibular joint of rats depends on inflammatory mechanisms and C-fibres sensitization.

BACKGROUND: P2X7 receptors are responsible for triggering inflammatory responses contributing to processes of pain in articular tissues. This study aimed to investigate whether the activation of the P2X7 receptor located in the temporomandibular joint (TMJ) tissues induces nociception through an inflammatory mechanisms and/or the activation of C-fibres (small-diameter primary afferents) of rats' TMJ. METHODS: The TMJ hypernociception induced by the activation of P2X7 receptor was assessed by measuring the behavioural nociceptive responses. After behavioural experiments, the animals were terminally anaesthetized and periarticular tissues were removed and homogenate for enzyme-linked immunosorbent assay, leukocyte infiltration and western blotting analysis. RESULTS: The nonselective P2X7 receptor agonist BzATP induced a dose-dependent TMJ nociception, which was blocked by the selective P2X7 receptor antagonist A-438079. The co-administration of the selective ß2-adrenoceptor antagonist (ICI-118,551) and the pre-treatment with cyclooxygenase inhibitor indomethacin or with the nonspecific selectin inhibitor Fucoidan significantly reduced BzATP-induced TMJ nociception. BzATP also induced an increase of pro-inflammatory cytokines TNFα, IL-1ß and CINC-1 levels, as well as leukocyte recruitment in TMJ tissue, effects that were reduced by A-438079. Moreover BzATP-induced TMJ nociception was inhibited in rats neonatal-treated with Capsaicin (depleting C-fibers). Finally, BzATP-induced an increase in TRPV1 expression in TMJ tissue. CONCLUSIONS: These findings suggest that P2X7 receptor activation in TMJ of rats induces nociceptive responses mediated by sympathomimetic amines, prostaglandins, leukocyte migration and increased levels of pro-inflammatory cytokines. Furthermore, the P2X7 receptor activation induces nociceptive responses dependent on the activation of the primary afferent nociceptors of rats' TMJ. SIGNIFICANCE: The activation of P2X7 receptors has an essential role in TMJ nociception and could be an interesting target to control the inflammatory pain in temporomandibular disorders.

Xanthan gum protects temporomandibular chondrocytes from IL­1ß through Pin1/NF­κB signaling pathway.

Temporomandibular disorder (TMD) is a complicated and multi­factorial disease related to inflammation and cartilage destruction. Intra­articular injection of xanthan gum (XG) has been demonstrated to protect the joint cartilage and reduce osteoarthritis progression. However, the role and mechanism of XG in TMD is still unclear. In the present study, chondrocytes were isolated from rats and identified by immunofluorescence. Cells were stimulated by XG or interleukin (IL)­1ß. Cell viability was analyzed by MTT assay. Tumor necrosis factor α (TNF­α) and IL­6 levels were determined by ELISA. The expression of monocyte chemoattractive protein­1 (MCP­1), inducible nitric oxide synthase (iNOS), collagens, matrix metalloproteinases (MMPs), peptidyl­prolyl isomerase 1 (Pin1) and phosphorylated nuclear factor κB (NF­κB) p65 (p­p65) was analyzed by quantitative PCR or western blotting. MMP activity was assessed by gelatin zymography. Compared with the control, XG treatment partially reversed the IL­1ß­reduced cell viability. In addition, IL­1ß stimulation increased inflammatory cytokine expression, including TNF­α, IL­6 secretion, MCP­1 and iNOS expression, whereas XG treatment reduced the expression of these inflammatory cytokines compared with that of the IL­1ß­stimulated cells. Additionally, XG increased the expression of collagen, but reduced MMP expression and activity as compared with that in the IL­1ß group. In addition, XG treatment prevented the IL­1ß­increased Pin1 and p­p65 expression. These data suggested that XG reduced the expression of inflammatory cytokines and may maintain the balance between collagens and MMPs partially through the Pin1/NF­κB signaling pathway in IL­1ß­stimulated temporomandibular chondrocytes. Therefore, XG may be useful in the treatment of TMD.

Poloxamer micellar system for intra-articular injection of 15-deoxy-Δ12,14-prostaglandin J2 with improved bioavailability and anti-inflammatory properties in the temporomandibular joint of rats.

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 J2 (15d-PGJ2) has shown important antinociceptive and anti-inflammatory activity. The present study evaluated the efficacy and viability of the micellar system of PL-15dPGJ2 in a formalin-induced acute pain model in the temporomandibular joint of rats. The PL-15dPGJ2 was prepared and characterized. The animals were pretreated with an intra-articular injection of PL-15dPGJ2 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-PGJ2 produced pain relief at lower concentrations and in a sustained manner compared with free 15d-PGJ2. 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-PGJ2 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.

IL-37 inhibits M1-like macrophage activation to ameliorate temporomandibular joint inflammation through the NLRP3 pathway.

OBJECTIVES: IL-37 has been identified as an important anti-inflammatory and immunosuppressive factor. This study was undertaken to explore how IL-37 affects M1/M2-like macrophage polarization and thus contributes to anti-inflammatory processes in the temporomandibular joint. METHODS: Western blotting, quantitative real-time PCR (qRT-PCR) and immunofluorescence were used to verify the IL-37-induced polarization shift from the M1 phenotype to the M2 phenotype, and the related key pathways were analysed by western blotting. Human chondrocytes were stimulated with M1-conditioned medium (CM) or IL-37-pretreated M1-CM, and inflammatory cytokines were detected. siRNA-IL-1R8 and MCC-950 were used to investigate the mechanism underlying the anti-inflammatory effects of IL-37. Complete Freund's adjuvant-induced and disc perforation-induced inflammation models were used for in vivo studies. Haematoxylin and eosin, immunohistochemical and safranin-O staining protocols were used to analyse histological changes in the synovium and condyle. RESULTS: Western blotting, qRT-PCR and immunofluorescence showed that IL-37 inhibited M1 marker expression and upregulated M2 marker expression. Western blotting and qRT-PCR showed that pretreatment with IL-37 suppressed inflammatory cytokine expression in chondrocytes. IL-37 inhibited the expression of NLRP3 and upregulated the expression of IL-1R8. Si-IL-1R8 and MCC-950 further confirmed that the anti-inflammatory properties of IL-37 were dependent on the presence of IL-1R8 and NLRP3. In vivo, IL-37 reduced synovial M1 marker expression and cartilage degeneration and increased M2 marker expression. CONCLUSION: IL-37 shifting of the polarization of macrophages from the pro-inflammatory M1 phenotype to the beneficial anti-inflammatory M2 phenotype seems to be a promising therapeutic strategy for treating temporomandibular joint inflammation.

Dioclea violacea lectin ameliorates inflammation in the temporomandibular joint of rats by suppressing intercellular adhesion molecule-1 expression.

Inflammation of temporomandibular joint (TMJ) tissues are the most common cause of pain conditions associated with temporomandibular disorders (TMDs). After a tissue and/or neural damage, the inflammatory response is characterized by plasma extravasation and leukocytes infiltration in the TMJ tissues, which in turn, release inflammatory cytokines cascades responsible for inflammatory pain. Lectins are glycoproteins widely distributed in nature that may exhibit anti-inflammatory properties. This study demonstrated by molecular docking and MM/PBSA that the lectin from Dioclea violacea (DVL) interacts favorably with α-methyl-D-mannoside, N-acetyl-D-glucosamine, and core1-sialyl-Lewis X which are associated with leukocytes migration during an inflammatory response. Wistar rats pretreated with intravenously injection of DVL demonstrated a significant inhibition of plasma extravasation induced by carrageenan (a non-neurogenic inflammatory inductor) and mustard oil (a neurogenic inflammatory inductor) in the TMJ periarticular tissues (p < 0.05; ANOVA, Tukey's test). In addition, DVL significantly reduced carrageenan-induced leukocyte migration in the TMJ periarticular tissues mediated by down-regulation of ICAM-1 expression. These results suggest a potential anti-inflammatory effect of DVL in inflammatory conditions of TMJ.

Heme oxygenase-1/biliverdin/carbon monoxide pathway downregulates hypernociception in rats by a mechanism dependent on cGMP/ATP-sensitive K+ channels.

OBJECTIVE AND DESIGN: To investigate the role of heme oxygenase-1 (HO-1), carbon monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats. MATERIALS AND METHODS: Mechanical threshold was assessed before and 4 h after TMJ arthritis induction in rats. Cell influx, myeloperoxidase activity, and histological changes were measured in the TMJ lavages and tissues. Trigeminal ganglion and periarticular tissues were used for HO-1, TNF-α, and IL-1ß mRNA time course expression and immunohistochemical analyses. Hemin (0.1, 0.3, or 1 mg kg-1), DMDC (0.025, 0.25, or 2.5 µmol kg-1), biliverdin (1, 3, or 10 mg kg-1), or ZnPP-IX (1, 3 or 9 mg kg-1) were injected (s.c.) 60 min before zymosan. ODQ (12.5 µmol kg-1; s.c.) or glibenclamide (10 mg kg-1; i.p.) was administered 1 h and 30 min prior to DMDC (2.5 µmol kg-1; s.c), respectively. RESULTS: Hemin (1 mg kg-1), DMDC (2.5 µmol kg-1), and BVD (10 mg kg-1) reduced hypernociception and leukocyte migration, which ZnPP (3 mg kg-1) enhanced. The effects of DMDC were counteracted by ODQ and glibenclamide. The HO-1, TNF-α, and IL-1ß mRNA expression and immunolabelling increased. CONCLUSIONS: HO-1/BVD/CO pathway activation provides anti-nociceptive and anti-inflammatory effects on the zymosan-induced TMJ hypernociception in rats.

Khat (Catha edulis) and its oral health effects: An updated review.

Khat or qat (Catha edulis) is a plant that grows in East Africa and southern Arabia. The leaves and twigs of this small tree are chewed by several millions of people worldwide for their stimulating amphetamine-like effects. The reported prevalence of khat chewing in Europe and the USA is on the rise, especially with global migration. Long-term khat chewing has several detrimental general and oral health effects. The aim of the present study was to review the current literature regarding khat use and its association with oral and dental diseases, with particular emphasis on its link with oral keratotic white lesions and oral cancer. We searched the literature to identify all relevant articles. Studies showed that khat is associated with several oral and dental conditions, including keratotic white lesions, mucosal pigmentation, periodontal disease, tooth loss, plasma cell stomatitis, and xerostomia. There are limited data on the incidence of dental caries among khat chewers. The evidence that khat chewing is a risk factor for oral cancer is still weak, and is mainly based on anecdotal case reports and uncontrolled studies.

Low-intensity pulsed ultrasound stimulation for mandibular condyle osteoarthritis lesions in rats.

OBJECTIVE: This study evaluated low-intensity pulsed ultrasound effects for temporomandibular joint osteoarthritis in adult rats. MATERIAL AND METHODS: Osteoarthritis-like lesions were induced in 24 adult rats' temporomandibular joints with low-dose mono-iodoacetate injections. The rats were divided into four groups: control and mono-iodoacetate groups, injected with contrast media and mono-iodoacetate, respectively, at 12 weeks and observed until 20 weeks; and low-intensity pulsed ultrasound and mono-iodoacetate + low-intensity pulsed ultrasound groups, injected with contrast media and mono-iodoacetate, respectively, at 12 weeks with low-intensity pulsed ultrasound performed from 16 to 20 weeks. Condylar bone mineral density, bone mineral content and bone volume were evaluated weekly with microcomputed tomography. Histological and immunohistochemical staining for matrix metalloproteinases-13 was performed at 20 weeks. RESULTS: At 20 weeks, the mono-iodoacetate + low-intensity pulsed ultrasound group showed significantly higher bone mineral density, bone mineral content and bone volume than the mono-iodoacetate group; however, these values remained lower than those in the other two groups. On histological and immunohistochemical analysis, the chondrocytes were increased, and fewer matrix metalloproteinases-13 immunopositive cells were identified in the mono-iodoacetate + low-intensity pulsed ultrasound group than mono-iodoacetate group. CONCLUSIONS: Low-intensity pulsed ultrasound for 2 weeks may have therapeutic potential for treating temporomandibular joint osteoarthritis lesions.

Tumor Necrosis Factor Alpha Signaling in Trigeminal Ganglion Contributes to Mechanical Hypersensitivity in Masseter Muscle During Temporomandibular Joint Inflammation.

AIMS: To determine the involvement of tumor necrosis factor alpha (TNFα) signaling in the trigeminal ganglion (TG) in the mechanical hypersensitivity of the masseter muscle during temporomandibular joint (TMJ) inflammation. METHODS: A total of 55 male Sprague-Dawley rats were used. Following injection of Complete Freund's Adjuvant into the TMJ, the mechanical sensitivities of the masseter muscle and the overlying facial skin were measured. Satellite glial cell (SGC) activation and TNFα expression in the TG were investigated immunohistochemically, and the effects of their inhibition on the mechanical hypersensitivity of the masseter muscle were also examined. Student t test or two-way repeated-measures analysis of variance followed by Bonferroni multiple comparisons test were used for statistical analyses. P < .05 was considered to reflect statistical significance. RESULTS: Mechanical allodynia in the masseter muscle was induced without any inflammatory cell infiltration in the muscle after TMJ inflammation. SGC activation and an increased number of TNFα-immunoreactive cells were induced in the TG following TMJ inflammation. Intra-TG administration of an inhibitor of SGC activity or of TNFα-neutralizing antibody depressed both the increased number of TG cells encircled by activated SGCs and the mechanical hypersensitivity of the masseter following TMJ inflammation. CONCLUSION: These findings suggest that persistent masseter hypersensitivity associated with TMJ inflammation was mediated by SGC-TG neuron interactions via TNFα signaling in the TG.

Inflammatory pain assessment in the arthritis of the temporomandibular joint in rats: A comparison between two phlogistic agents.

Temporomandibular joint (TMJ) disorders are a group of conditions that result in TMJ pain, which frequently limits basic daily activities. Experimental models that allow the study of the mechanisms underlying these inflammatory and pain conditions are of great clinical relevance. The aim of this study was to evaluate nociception, inflammation and participation of the macrophage/microglia cells in the arthritis of the TMJ induced by two phlogistic agents. 84 rats were divided into 2 groups: Zy, which received zymosan intra-articularly, or Cg, which received carrageenan intra-articularly. Mechanical nociception, total leukocyte influx to the synovial fluid and histopathological analyses were evaluated in the TMJ. The participation of macrophage/microglia located in trigeminal ganglia (TG) and in the subnucleus caudalis (V-SnC) was assessed immunohistochemically. Both agents induced mechanical hyperalgesia 6h after the induction, but a more persistent algesic state was perceived in the Cg group, which lasted for 120h. Even though both groups presented increased leukocyte influx, the Zy-group presented a more intense influx. Zymosan recruited resident macrophage in the trigeminal ganglia 24h after the injection. In the V-SnC, the group Cg presented a more prolonged immunolabeling pattern in comparison with the group Zy. It can be concluded that zymosan induced a more intense infiltrate and peripheral nervous changes, while Cg lead to a moderate TMJ inflammation with prominent changes in the V-SnC.

[Temporomandibular joint arthropathy in situ steroid injection]. / Arthropathie temporomandibulaire après infiltration cortisonique in situ.

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.

The effect of acute unilateral inflammation of the equine temporomandibular joint on the kinematics of mastication.

REASONS FOR PERFORMING STUDY: Diseases of the temporomandibular joint (TMJ) are well reported in man and some domestic animals other than the horse. The pathophysiology of equine TMJ disease and the effects of disease on the kinematics of mastication are unknown. OBJECTIVES: To determine whether transient unilateral inflammation of the equine TMJ results in alterations in the masticatory cycle. STUDY DESIGN: An experimental controlled study utilising 6 horses of various ages with normal dentition. METHODS: Each horse was equipped with an optical motion tracking (kinematic) system. Horses were observed chewing grass hay over 3 min intervals. Regardless of the initial side of the power stroke in the masticatory cycle, lipopolysaccharide (LPS) was injected in the left TMJ in each horse and the horses were reassessed after 6 h. RESULTS: Four horses developed effusion of the injected TMJs; 2 of these also began quidding. All horses injected on the original side of the power stroke switched sides while the 2 injected on the contralateral side did not. All horses developed reduced vertical pitch (vertical opening) of the mandible. Overall, rostrocaudal movement of the mandible did not change; however, the timing of this movement relative to the phase of the masticatory cycle did. Injection with LPS did not affect the amount of lateral movement of the mandible. CONCLUSIONS: Injection of LPS into the TMJ significantly altered the masticatory cycle compared with baseline values representing avoidance behaviour due to inflammation of the joint, despite which the horses continued to eat using the contralateral mandible. Lipopolysaccharide administration also led to quidding and a loss of feed efficiency (in some individuals).

Infliximab partially alleviates the bite force reduction in a mouse model of temporomandibular joint pain.

Temporomandibular joint (TMJ) disorder is clinically important because of its prevalence, chronicity, and therapy-refractoriness of the pain. In this study, we investigated the effect of infliximab in a mouse model of TMJ pain using a specially-engineered transducer for evaluating the changes in bite force (BF). The mice were randomly divided into three groups (7 mice per group): the control group, the complete Freund's adjuvant (CFA) group, and the infliximab group. BF was measured at day 0 (baseline BF). After measuring the baseline BF, CFA or incomplete Freund's adjuvant was injected into both TMJs and then the changes in BF were measured at days 1, 3, 5, 7, 9, and 13 after the TMJ injection. For measuring the BF, we used a custom-built BF transducer. Control, CFA, and infliximab groups showed similar baseline BF at day 0. From day 1, a significant reduction in BF was observed in the CFA group, and this reduction in BF was statistically significant compared to that in the control group (P < 0.05). This reduction in BF was maintained until day 7, and BF started to recover gradually from day 9. In the infliximab group also, the reduction in BF was observed on day 1, and this reduction was maintained until day 7. However, the degree of reduction in BF was less remarkable compared to that in the CFA group. The reduction in BF caused by injection of CFA into the TMJ could be partially alleviated by the injection of anti-tumor necrosis factor alpha, infliximab.

Can experimentally evoked pain in the jaw muscles or temporomandibular joint affect anterior bite force in humans?

AIMS: To test the hypothesis that experimental pain in the masseter muscle or temporomandibular joint (TMJ) will decrease the anterior maximum voluntary bite force (MVBF) and jaw muscle activity in relation to the perceived effort. METHODS: Sixteen volunteers participated in two experimental sessions. Participants were injected with 0.2 mL of monosodium glutamate (1.0 M) into either the masseter muscle or TMJ. The MVBF and corresponding electromyographic (EMG) activity of the masseter, anterior temporalis, and digastric muscles were recorded 10 times at an interval of 2 minutes before and after injection. Pain was measured using a visual analog scale and McGill Pain Questionnaire. In addition, participants were asked how they perceived the interference of pain on their biting performance. The data analysis included a two-way analysis of variance model and t test. RESULTS: There was no significant difference in peak pain intensity (P = .066) and duration of pain (P = .608) between painful muscle and TMJ injections, but TMJ injection produced a significantly larger area under the curve (P = .005) and a significantly higher pain rating index (P = .030). Pain in the muscle (P = .421) and TMJ (P = .057) did not significantly change the MVBF from baseline levels. The EMG activity also did not differ significantly from baseline levels during muscle pain. However, there was a significant increase (P = .028) in the EMG activity of the anterior temporalis and a significant decrease (P = .010) in the EMG activity of the anterior digastric muscle compared to baseline during TMJ pain. Subject-based reports also revealed that in the majority of cases (62.5%), pain did not interfere with the MVBF task. CONCLUSION: Experimental pain from either masseter muscle or TMJ did not affect the MVBF, in accordance with the subject-based reports. Jaw muscle activity, except for EMG activity of the anterior temporalis and anterior digastric muscles during TMJ pain, also remained unaffected by pain. The findings suggest that it is not pain in itself but rather how pain is perceived that may lead to adaptation of motor function, supporting an integrated pain adaptation model.

Infliximab Partially Alleviates the Bite Force Reduction in a Mouse Model of Temporomandibular Joint Pain

Temporomandibular joint (TMJ) disorder is clinically important because of its prevalence, chronicity, and therapy-refractoriness of the pain. In this study, we investigated the effect of infliximab in a mouse model of TMJ pain using a specially-engineered transducer for evaluating the changes in bite force (BF). The mice were randomly divided into three groups (7 mice per group): the control group, the complete Freund's adjuvant (CFA) group, and the infliximab group. BF was measured at day 0 (baseline BF). After measuring the baseline BF, CFA or incomplete Freund's adjuvant was injected into both TMJs and then the changes in BF were measured at days 1, 3, 5, 7, 9, and 13 after the TMJ injection. For measuring the BF, we used a custom-built BF transducer. Control, CFA, and infliximab groups showed similar baseline BF at day 0. From day 1, a significant reduction in BF was observed in the CFA group, and this reduction in BF was statistically significant compared to that in the control group (P < 0.05). This reduction in BF was maintained until day 7, and BF started to recover gradually from day 9. In the infliximab group also, the reduction in BF was observed on day 1, and this reduction was maintained until day 7. However, the degree of reduction in BF was less remarkable compared to that in the CFA group. The reduction in BF caused by injection of CFA into the TMJ could be partially alleviated by the injection of anti-tumor necrosis factor alpha, infliximab.

Tephrosia toxicaria†Pers. reduces temporomandibular joint inflammatory hypernociception: the involvement of the HO-1 pathway.

BACKGROUND: We investigated both the efficacy and the sub-chronic toxicity of Tephrosia toxicaria Pers. in the zymosan-induced temporomandibular joint (TMJ) inflammatory hypernociception in rats evaluating the possible role of heme oxygenase-1 (HO-1). METHODS: Rats were pretreated with T. toxicaria (0.2, 2.0 or 20 mg/kg) 60 min before the intra-articular injection of zymosan (2 mg, 40 µL) in the left TMJ. In another series of experiments, rats were treated with ZnPP-IX (3 mg/kg), a specific HO-1 inhibitor, before T. toxicaria (20 mg/kg). Von Frey test was used to evaluate inflammatory hypernociception (g) 4 h after zymosan injection. Six hours after zymosan injection, the synovial lavage was collected for total cell count and myeloperoxidase (MPO) activity, and joint tissue for histopathological analysis and immunohistochemistry for HO-1. To evaluate the sub-chronic toxicity, mice received T. toxicaria (20 mg/kg) or saline once a day for 14 days to analyse body mass, organ weight and biochemical parameters. RESULTS: T. toxicaria partially reversed the zymosan-induced head withdrawal threshold, the number of cells and the MPO activity. T. toxicaria reduced the inflammatory cell influx in the synovial membrane. TMJ immunohistochemical analyses treated with T. toxicaria showed increased HO-1 expression. These effects of T. toxicaria were not observed in the presence of ZnPP-IX. T. toxicaria treatment for 14 days did not show significant signs of toxicity when administrated to mice. CONCLUSIONS: T. toxicaria did not produce any signs of toxicity and effectively decreased zymosan-induced TMJ inflammatory hypernociception dependent, at least in part, upon the HO-1 pathway integrity.