Corticosteroid injections in the temporomandibular joint temporarily alleviate pain and improve function in rheumatoid arthritis.

OBJECTIVES: To evaluate the effect of corticosteroid injections in the painful temporomandibular joint (TMJ) of patients with rheumatoid arthritis (RA) in relation to systemic inflammatory activity. METHOD: Examination of 35 patients (median age 54 years; 89% female) included maximum mouth opening capacity, degree of anterior open bite (AOB), TMJ pain intensity at rest, and crepitus. Serum levels of rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serotonin, and plasma levels of interleukine-1ß (IL-1ß) were determined. Out of the 70 examined joints, 53 joints received a corticosteroid (methylprednisolone) injection after the clinical examination at baseline (T0). The examination was repeated for all patients at T1 (median 3.1 weeks after T0), and for 21 patients at T2 (median 6.3 weeks after T1), of whom 20 patients received a second injection at T1. RESULTS: Maximum mouth opening capacity significantly increased, and TMJ pain intensity significantly decreased between T0 and T1, but these improvements were no longer present at T2. No differences were found in AOB between the time points. Of the joints that received an injection at T0, 19 joints had pretreatment crepitus, which resolved in eight joints at T1. No correlations were found between the change in mouth opening capacity or TMJ pain intensity and ESR, CRP, serotonin, or IL-1ß. CONCLUSIONS: Methylprednisolone injections in the TMJ alleviate pain and improve mouth opening capacity for approximately 3 weeks, allowing patients to perform jaw exercises during this timeframe of temporary relief. It thus seems useful for the short-term management of TMJ involvement in RA. Key Points • In rheumatoid arthritis, corticosteroid injection in the temporomandibular joint alleviates pain and improves function. • The clinical improvement achieved with methylprednisolone injections lasts for approximately 3 weeks. • Corticosteroid injections could be used to facilitate and support additional noninvasive, conservative treatment options.

TMJ Pain and Crepitus Occur Early Whereas Dysfunction Develops Over Time in Rheumatoid Arthritis.

AIMS: To investigate inflammatory mediator levels in TMJ synovial fluid (SF) and blood and to investigate clinical TMJ symptoms in relation to general and TMJ symptom duration in patients with rheumatoid arthritis (RA). METHODS: Examination of 80 TMJs (68 patients; median age 55 years; 85% women) included the following variables: TMJ pain at rest, maximum mouth opening, and palpation; jaw movement capacity; number of painful movements; crepitus; and degree of anterior open bite. Levels of tumor necrosis factor (TNF), TNF soluble receptor II, interleukin 1ß, IL-1 receptor antagonist, IL-1 soluble receptor II, and serotonin in TMJ SF and blood; systemic disease activity; and duration of general and TMJ symptoms were assessed. General symptom duration ≤ 2 years was considered early RA. RESULTS: TMJ symptoms predominantly developed within 5 years following general symptom onset. Logistic regression analysis showed that number of involved joints, general pain, maximum mouth opening, anterior open bite, and TNF plasma levels combined explained 46% of the distinction between early and established RA. Furthermore, TMJ pain at rest and maximum mouth opening, contralateral laterotrusion, painful movements, crepitus, and SF TNF levels combined explained 35% of the distinction. In these analyses, higher general pain and maximum mouth opening, TMJ pain on maximum mouth opening, and crepitus were associated with early RA. CONCLUSION: This study indicates that TMJ pain and crepitus in RA usually occur within 2 years following general symptom onset. Pain-related dysfunction and structural changes develop with time. TNF in plasma and TMJ SF are associated with this development. This makes early (clinical) recognition of pain and inflammation important, enabling early treatment to minimize later irreversible damage.

Expression of 5-HT3 receptors and TTX resistant sodium channels (Na(V)1.8) on muscle nerve fibers in pain-free humans and patients with chronic myofascial temporomandibular disorders.

BACKGROUND: Previous studies have shown that 5-HT3-antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT3-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (NaV) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT3A-receptors alone and in combination with NaV1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls. METHODS: Three microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT3A-receptors and NaV1.8 sodium-channels. RESULTS: A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT3A-receptors. The expression of NaV1.8 by 5-HT3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P < .001). In the patients, significantly more fibers per section were found with an average of 3.8 ± 3 fibers per section in the masseter muscle compared to 2.7 ± 0.2 in the healthy controls (P = .024). Further, the frequency of nerve fibers that co-expressed NaV1.8 and 5-HT3A receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P < .001). CONCLUSIONS: This study showed that the 5-HT3A-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT3A-receptors in the masseter of women with myofascial TMD compared to healthy women. These findings indicate that 5-HT3-receptors might be up-regulated in myofascial TMD and could serve as potential biomarkers of chronic muscle pain.

Temporomandibular joint bone tissue resorption in patients with early rheumatoid arthritis can be predicted by joint crepitus and plasma glutamate level.

The aim was to investigate whether bone tissue resorption in early RA is related to crepitus of the temporomandibular joint (TMJ) and systemic levels of inflammatory mediators and markers and sex steroid hormones. Twentynine women and 18 men with recently diagnosed RA were examined for TMJ bone erosions with computerized tomography and TMJ crepitus was assessed. Blood samples were analyzed for glutamate, 5-HT, TNF, IL-1beta, IL-6, VEGF, inflammatory markers, and estradiol, progesterone and testosterone. The TMJ erosion score was positively correlated to glutamate, and TMJ crepitus where crepitus, glutamate and ESR explained 40% of the variation in the bone erosion score. In the patients without crepitus, bone erosion score was positively correlated to glutamate, which was not the case in the patients with crepitus. In conclusion, the results of this study show that TMJ bone tissue resorption can be predicted by TMJ crepitus and glutamate in early RA.

Glutamate-induced temporomandibular joint pain in healthy individuals is partially mediated by peripheral NMDA receptors.

AIM: To determine if glutamate injected into the healthy temporomandibular joint (TMJ) evokes pain through peripheral N-methyl-D-aspartate (NMDA) receptors and if such pain is influenced by sex or sex steroid hormones. METHODS: Sixteen healthy men and 36 healthy women were included and subjected to two randomized and double-blind intra-articular injections of the TMJ. Experimental TMJ pain was induced by injection of glutamate (1.0 mol/L) and NMDA block was achieved by co-injection of the NMDA antagonist ketamine (10 mmol/L). The TMJ pain intensity in the joint before and during a 25-minute postinjection period was continuously recorded on an electronic visual analog scale (0 to 10). Estradiol, progesterone, and testosterone levels in serum were analyzed. RESULTS: Glutamate-induced pain showed a median (25/75 percentile) duration of 8.3 (5.2/12.2) minutes. The peak pain intensity was 6.1 (4.2/8.2), the time to peak was 50 (30/95) seconds, and the area under the curve was 59 (29/115) arbitrary units. The women reported higher maximum pain intensity than the men and shorter time to peak. The sex hormone levels were not significantly related to the glutamate-induced TMJ pain. NMDA block significantly reduced the glutamate-induced TMJ pain, mainly in the women. There were no significant correlations between sex hormone levels and the effects of NMDA block for any pain variable. CONCLUSION: Glutamate evokes immediate pain in the healthy human TMJ that is partly mediated by peripheral NMDA receptors in the TMJ.

Endogenous glutamate in association with inflammatory and hormonal factors modulates bone tissue resorption of the temporomandibular joint in patients with early rheumatoid arthritis.

PURPOSE: The aim of this study was to investigate the relation between plasma level of glutamate and extent of radiographic bone erosion of the temporomandibular joint (TMJ) in patients with early rheumatoid arthritis (RA) in relation to inflammatory disease activity as well as estradiol and testosterone. MATERIALS AND METHODS: A total of 47 patients (29 women and 18 men) of whom 24 were seropositive were included shortly after being diagnosed with RA. Radiographic signs of bone tissue resorption (erosions) in the TMJ were recorded by cone-beam CT images, and an erosion score (0 to 24) was calculated for each patient. Venous blood was analyzed for rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, leukocyte particle count, glutamate, estradiol, and testosterone. Nonparametric statistical methods were used in the analysis. RESULTS: Resorptive changes of the TMJ were found in a major part of the patients. There was a significant positive correlation between plasma level of glutamate and extension of radiographic erosions that was strongest in the patients with low levels of C-reactive protein, estradiol, or testosterone. By contrast, erosions were correlated with C-reactive protein in patients with high levels of estradiol. The highest levels of glutamate were found in patients with low levels of C-reactive protein and estradiol. CONCLUSIONS: This study shows that a majority of patients with early RA presents radiographic signs of bone tissue resorption of the TMJ and that circulating glutamate is associated with the extent of these changes. The relationship between glutamate and bone resorption seems to be influenced by systemic inflammatory activity as well as estradiol and testosterone levels.

Gingivitis and periodontitis are related to repeated high levels of circulating tumor necrosis factor-alpha in patients with rheumatoid arthritis.

BACKGROUND: Several studies have indicated a relationship between rheumatoid arthritis and periodontal disease. The aim of this study was to investigate the association between the circulating proinflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, prostaglandin E(2), serotonin, rheumatoid factor, and periodontitis in patients with rheumatoid arthritis. METHODS: Nineteen patients, 17 women and two men, with rheumatoid arthritis were included. These patients had been examined repeatedly (average of three times) with regard to inflammatory markers and mediators from blood samples. Their teeth, excluding third molars, were examined with regard to number, clinical attachment level (CAL), probing depth (PD), and gingival bleeding on probing (BOP). Assessment of furcation involvement and increased tooth mobility was also made. All patients were non-smokers. Thirty healthy individuals, 20 women and 10 men, were included as a reference regarding TNF-alpha. RESULTS: Patients with high levels of time-averaged TNF-alpha from repeated plasma samples had a higher frequency of BOP as well as increased CAL and PD compared to those with low levels. CONCLUSION: Gingivitis and periodontitis are related to high levels of circulating TNF-alpha in patients with rheumatoid arthritis.

Temporomandibular joint pressure pain threshold is systemically modulated in rheumatoid arthritis.

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

Intramuscular injection of granisetron into the masseter muscle increases the pressure pain threshold in healthy participants and patients with localized myalgia.

OBJECTIVES: The aims of this study were to experimentally investigate whether an intramuscular injection of the 5-HT(3) antagonist granisetron into the masseter muscle increases the mechanical pain threshold in healthy participants and reduces masseter muscle pain or allodynia in patients with craniofacial myalgia. METHODS: Eighteen patients with bilateral localized myalgia of the masseter muscle and 24 healthy participants participated in this randomized, double-blind study, in which granisetron was injected on one side and isotonic saline on the other side. Pain (Visual Analog Scale) and pressure pain threshold (PPT) were recorded before and during 30 minutes after injections and the changes from baseline were analyzed with analysis of variance. RESULTS: In both groups, the PPT increased after injection of granisetron whereas it decreased after saline. The difference between substances was significant (patients: P=0.016; healthy participants: P=0.029). In the healthy participants there was also a significant time effect (P<0.001) and an interaction between time and substance (P=0.022). The post-hoc test showed that the difference between substances was significant 0 to 15 minutes after injections (Bonferroni t test; P<0.05). The pain intensity from the masseter muscle did not differ between substances, but there was a significant time effect (P<0.001) and an interaction between time and substance (P<0.001). The post-hoc test showed significantly lower pain intensity on the granisetron side 0 to 2 minutes after injections (Bonferroni t test; P<0.05). CONCLUSIONS: This study indicates that intramuscular injection of granisetron into the masseter muscle increases the PPT in healthy participants and in patients with craniofacial myalgia.

Effects of isometric contraction on intramuscular level of neuropeptide Y and local pain perception.

OBJECTIVE: The release of neuropeptide Y (NPY) is reported to increase in ischemic conditions and may thus be involved in chronic myalgia. The purpose of this study was to investigate the effect of isometric contraction on intramuscular levels of NPY in relation to local pain development. MATERIAL AND METHODS: Intramuscular microdialysis was performed in the masseter and trapezius muscles to determine NPY levels before, during, and after isometric contraction in 16 healthy females. Pain intensity was assessed simultaneously with VAS. Repeated measures ANOVA, t-test, and Pearson correlation analysis were used for statistical analyses. RESULTS: The level of NPY in the trapezius muscle was increased during and after contraction, while there was no change in the masseter muscle. The level of NPY before contraction was higher in the masseter muscle than in the trapezius muscle, and the levels in the two muscles were correlated before and during contraction. Low-level pain in both muscles after probe insertion increased significantly during contraction, but the pain was not correlated to the NPY level. CONCLUSIONS: Pain is developed in the trapezius and masseter muscles during repeated isometric contraction. The NPY level is increased in the trapezius muscle but is not associated with the pain development.

Insufficient endogenous control of tumor necrosis factor-alpha contributes to temporomandibular joint pain and tissue destruction in rheumatoid arthritis.

OBJECTIVE: To investigate whether pain and tissue destruction in the temporomandibular joint (TMJ) of patients with rheumatoid arthritis (RA) are influenced by plasma levels of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) or the soluble receptor TNFsRII. METHODS: Fifty-one patients with RA were included. TMJ resting pain intensity, pain intensity upon mandibular movement, tenderness to palpation, pressure-pain threshold, and presence of anterior open bite were assessed. Venous blood was obtained for analysis of TNF-alpha, TNFsRII, and inflammatory markers. RESULTS: A total of 29 patients had TMJ pain and 22 patients had anterior open bite. In the group of patients with TMJ pain, 12 had anterior open bite and 17 did not. In the patients without TMJ pain 10 patients had anterior open bite and 12 did not. Patients with or without anterior open bite did not differ regarding any investigated variable. Plasma TNF-alpha and TNFsRII were positively correlated in the total patient sample. TNFsRII was negatively correlated with degree of anterior open bite in patients with TMJ pain but positively correlated with TMJ pressure-pain threshold in patients with elevated plasma TNF-alpha. CONCLUSION: Our results indicate that insufficient systemic endogenous control of TNF-alpha seems to contribute to TMJ pain and tissue destruction in RA.

Effects of local serotonin administration on pain and microcirculation in the human masseter muscle.

AIMS: To investigate whether exogenously administered 5-hydroxytryptamine (5-HT) at high or low concentration influences pain and microcirculation in the human masseter muscle. METHODS: In 12 healthy female subjects, 5-HT in 2 concentrations (0.1 micromol/L and 1,000 micromol/L) and isotonic saline were injected into the masseter muscles in a randomized and balanced double-blind manner. The pain intensity after injections was recorded with Borg's rating scale, and intramuscular blood flow was monitored continuously during the experiment with a laser-Doppler technique. Nonparametric statistics were used for analyses. RESULTS: Administration of 5-HT at 1,000 micromol/L induced significantly more pain than saline (Wilcoxon: P < .05), while there was no difference between 5-HT at 0.1 micromol/L and saline. The blood flow did not change significantly after injection of 5-HT at either concentration compared to saline. However, changes in pain intensity and blood flow were positively correlated after injection of 5-HT at 1,000 micromol/L (Spearman: P < .05). CONCLUSION: Intramuscular administration of 5-HT at 1,000 micromol/L into the human masseter muscle induced pain, but 5-HT did not have any effect on local blood flow at either concentration.

Tumor necrosis factor-alpha in temporomandibular joint synovial fluid predicts treatment effects on pain by intra-articular glucocorticoid treatment.

The aim of this study was to investigate the influence of tumor necrosis factor-alpha (TNF-alpha) in temporomandibular joint (TMJ) synovial fluid and blood on the treatment effect on TMJ pain by intra-articular injection of glucocorticoid in patients with chronic inflammatory TMJ disorders. High pretreatment level of TNF-alpha in the synovial fluid was associated with a decrease of TNF-alpha and elimination of pain upon maximal mouth opening. Elimination of this TMJ pain was accordingly associated with decrease in synovial fluid level of TNF-alpha. There was also a significant decrease of C-reactive protein and TMJ resting pain after treatment. In conclusion, this study indicates that presence of TNF-alpha in the synovial fluid predicts a treatment effect of intra-articular injection of glucocorticoid on TMJ movement pain in patients with chronic TMJ inflammatory disorders.

Serotonergic mechanisms influence the response to glucocorticoid treatment in TMJ arthritis.

The aims of this study were to investigate the influence of serotonin (5-HT) on the effects of intra-articular injections of glucocorticoid on pain of the temporomandibular joint (TMJ) in patients with inflammatory disorders of the TMJ. The pretreatment synovial fluid 5-HT was negatively, and plasma 5-HT positively, correlated to change in TMJ pain after treatment. The pretreatment plasma 5-HT was positively correlated to change in pressure-pain threshold after treatment. In conclusion, this study shows that local and systemic serotonergic mechanisms partly determine the effect of intra-articular glucocorticoid treatment on TMJ pain in patients with chronic TMJ arthritis of systemic nature, while change in pressure-pain threshold over the TMJ is influenced by systemic serotonergic mechanisms.

Reduction of temporomandibular joint pain after treatment with a combination of methotrexate and infliximab is associated with changes in synovial fluid and plasma cytokines in rheumatoid arthritis.

The aims were to investigate the effect of intravenous infusions of the tumor necrosis factor-alpha (TNF-alpha) antibody infliximab on symptoms and signs of temporomandibular joint (TMJ) involvement in relation to effects on synovial fluid and plasma proinflammatory TNF-alpha, interleukin-1beta (IL-1beta) and interleukin-6 as well as antiinflam matory soluble TNF receptor II (TNF-sRII), interleukin-1 receptor antagonist (IL-1ra), soluble IL-1 receptor II (IL-1sRII) and interleukin-10 (IL-10) in patients with active rheumatoid arthritis (RA). Nineteen patients with TMJ involvement taking methotrexate were included in the study. TMJ and general joint pain intensity as well as pain on mandibular movements, tenderness to digital palpation, pressure pain threshold and maximum mouth-opening capacity were assessed in a clinical examination. The effect of infliximab was assessed after 2 and 14 or 22 weeks. TMJ synovial fluid and venous blood were collected for cytokine analysis at all occasions while determination of erythrocyte sedimentation rate and C-reactive protein were performed at baseline and at long-term follow-up only. Reduction of TMJ pain was associated with raised levels of synovial fluid TNF-sRII and IL-1sRII as well as raised plasma levels of IL-1ra and IL-10. Decreased erythrocyte sedimentation rate was associated with decreased tenderness to digital palpation. Reduced general joint pain intensity was associated with reduced plasma levels of IL-6 and C-reactive protein. In conclusion, systemic treatment with a combination of infliximab and methotrexate reduces TMJ pain in RA in association with an increase in anti-inflammatory cytokines and receptors in synovial fluid and plasma.

The effect on mechanical pain threshold over human muscles by oral administration of granisetron and diclofenac-sodium.

Previous studies indicate that plasma levels of serotonin (5-HT) and intramuscular prostaglandin E2 (PGE2) participate in determining the mechanical pain threshold and tolerance level to pressure applied on the skin over healthy muscles. Other studies reported gender differences regarding responses to noxious stimuli. The present study aimed to determine whether the mechanical pain threshold of healthy muscles is influenced by oral administration of 5-HT3 or PGE2-inhibitors and if there are any gender differences in this respect. Ten healthy female subjects and 10 age-matched healthy male subjects participated in the study, which was randomized and double blind with crossover design. Granisetron (5-HT3-antagonist), diclofenac-sodium (PGE2-antagonist) and placebo were administered for 3 days. The pressure pain threshold (PPT) was recorded bilaterally with an algometer over certain orofacial, trunk, and limb muscles before and after administration of the antagonists. The PPT over all muscles combined increased after administration of granisetron. There was no change after administration of placebo. The difference between granisetron and placebo was significant for the trapezius and tibialis anterior muscles. Diclofenac-sodium did not influence the PPT and there was no difference compared to placebo. Although the basal PPT values were lower in females, the PPT response to granisetron differed significantly between genders only in the tibialis anterior muscle. In conclusion, the results of this study showed that oral administration of the 5-HT3-antagonist granisetron increased the PPT over healthy trunk and limb muscles but not over orofacial muscles, and that the response in the limb muscles was greater in males.

Topical review: new insights into the pathology and diagnosis of disorders of the temporomandibular joint.

The collection of conditions affecting the temporomandibular joint (TMJ) and masticatory muscles, the so-called temporomandibular disorders, can be classified according to the Research Diagnostic Criteria for Temporomandibular Disorders. Of the 3 subgroups--muscle disorders (Group I); disc displacements (Group II); and arthralgia, arthritis, and arthrosis (Group III)--the muscle disorders are most frequently seen in community samples; Group II and Group III diagnoses are less prevalent. This may explain the relative scarcity of studies involving intracapsular TMJ disorders. In this review, new insights into the functional anatomy, imaging, and pathology of disorders of the TMJ are presented. Studies of TMJ dynamics may provide insight into the functional anatomy of the TMJ and thereby into the consequences of Group II and Group III disorders. The clinical use of imaging modalities such as computed tomography and magnetic resonance imaging for the TMJ and related structures remains controversial. Nevertheless, imaging is regularly used in the diagnosis of some Group II and Group III disorders. Magnetic resonance imaging may be of use not only for the visualization of disc displacements but also for the study of bone mineral density of the condyle. Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) play an important role in TMJ pathology. For example, IL-1beta, which has been associated with TMJ pain, hyperalgesia, and anterior bite opening, is mostly absent in the synovial fluid of healthy joints. Since both IL-1 and TNFalpha are involved in the development of chronic pain and joint destruction, they may be the targets for specific treatments. While the advances reviewed in this paper are significant, multidisciplinary efforts and formation of international research collaborations will be necessary to continue advancement in the understanding of TMJ pathology and diagnosis.

Progression of radiographic changes in the temporomandibular joints of patients with rheumatoid arthritis in relation to inflammatory markers and mediators in the blood.

The aim of this study was to investigate longitudinal radiographic changes in the temporomandibular joint (TMJ) with clinical involvement of rheumatoid arthritis (RA) and its relation to the blood level of inflammatory mediators and markers. Sixteen patients were investigated by computed tomography on two occasions 25-46 months apart. The radiographs were assessed independently for changes in presence of erosions, sclerosis, flattening, osteophytes, and subchondral pseudocysts. The serum (S) or plasma (P) concentrations of C-reactive protein (CRP), thrombocyte particle concentration, scrotonin (S-5-HT and P-5-HT), tumor necrosis factor alpha, interleukin-1 receptor antagonist, tumor necrosis factor soluble receptor type II, interleukin-1 soluble receptor type II (P-IL-1sRII) and interleukin 6 as well as the erythrocyte sedimentation rate (ESR) were measured. The radiographic status showed no consistent or significant change during the observation period, but the individual variation was considerable. The radiographic signs of erosion and sclerosis varied most. Regression of erosions was associated with high S-5-HT and P-IL-1sRII, while progression of erosions was associated with high P-5-HT. Regression of sclerosis was associated with an increase in P-5-HT and high ESR. Progression of flattening was associated with high CRP. In conclusion, this study indicates that the progression of radiographic changes that occurs in the TMJ of patients with well-controlled RA during a period of 25-46 months seems to be related to the blood levels of CRP, 5-HT, and IL-1sRII. However, only minor progression can be expected to occur, and with considerable individual variation.

Influence of serotonin on the analgesic effect of granisetron on temporomandibular joint arthritis.

The influence of circulating serotonin (5-HT) on the effects of intra-articular administration of granisetron on temporomandibular joint (TMJ) pain was investigated in 11 patients with chronic polyarthritides. An analgesic effect superior to placebo has been shown previously. The change in TMJ movement pain intensity was negatively correlated to circulating 5-HT; that is, the higher the 5-HT before injection, the greater the reduction of pain intensity. The resting pain intensity reduction was not related to 5-HT. In conclusion, this study indicates a stronger short-term analgesic effect on TMJ movement pain by intra-articular administration of the 5-HT3 receptor antagonist granisetron in patients with high levels of circulating 5-HT.

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

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