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.

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.

Pressure pain thresholds in the craniofacial region of female patients with rheumatoid arthritis.

AIMS: To determine the temporomandibular joint (TMJ) pressure pain threshold (PPT) in female patients with rheumatoid arthritis (RA) and TMJ involvement in comparison with healthy females, in order to determine its clinical usefulness for local pain assessment. METHODS: Forty-two female patients with the diagnosis of RA, 17 of them positive and 25 negative for rheumatoid factor were investigated, as well as 17 healthy females. A pressure algometer was used to assess the PPT over the TMJ and (as a reference) the center of the glabella. The mean of the second and third TMJ PPT was used in the analysis, and the ratio between the TMJ PPT and the PPT of the reference site (PPT ratio) was calculated. Temporomandibular joint resting pain and pain upon maximum voluntary mouth opening was assessed by a visual analog scale on each side. RESULTS: The TMJ PPT (median/10th to 90th percentile) and PPT ratio were significantly lower in the RA patients (148/64 to 220 and 0.63/0.40 to 1.01, respectively) than in the healthy individuals (217/111 to 352 and 0.85/0.51 to 1.25), but the overlap was considerable. CONCLUSION: This study shows that the PPT of the TMJ in RA patients is lower than in healthy individuals and that it can be used for pain assessment. However, the clinical use of the TMJ PPT and PPT ratio measurements alone is limited from a diagnostic point of view.

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.

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.

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.

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.

Blood serotonin and joint pain in seropositive versus seronegative rheumatoid arthritis.

AIM: To investigate whether blood serotonin (5-hydroxytryptamine) (5-HT) modulates musculoskeletal pain differently in seropositive and seronegative rheumatoid arthritis (RA). METHODS: Patients with temporomandibular joint (TMJ) involvement of seropositive RA (33 patients) or seronegative RA (28 patients) and 26 healthy individuals were included. TMJ pain, general musculoskeletal pain, plasma and serum 5-HT, acute phase reactants and thrombocyte count were investigated. RESULTS: The patients with seropositive RA had higher serum (median = 1130 nmol/l) and plasma (55 nmol/l) levels of 5-HT than the healthy individuals (704 nmol/l, p = 0.044 and 23 nmol/l, p < 0.001, respectively), and higher plasma levels of 5-HT than the seronegative patients (14 nmol/l, p < 0.001). There was no significant correlation between serum and plasma levels of 5-HT in any group. In the seropositive RA patients, positive correlations were found between serum levels of 5-HT and the number of painful mandibular movements (r(s) = 0.36, n = 33, p = 0.042), as well as pain on maximum mouth opening (r(s) = 0.41, n = 24, p = 0.047) and tenderness to digital palpation (r(s) = 0.49, n = 33, p = 0.003). In the healthy individuals, there was a negative correlation between plasma level of 5-HT and the TMJ pressure pain threshold (r(s) = -0.47, n = 20, p = 0.037). CONCLUSION: Peripheral serotonergic pain mechanisms seem to be activated by blood 5-HT in patients with seropositive RA, in contrast to seronegative patients.

Ropivacaine for dental anesthesia: a dose-finding study.

PURPOSE: The purpose of this study was to determine the optimal concentration and volumes of ropivacaine for dental anesthesia as regards onset and duration of action. SUBJECTS AND METHODS: Thirty healthy individuals with a mean age of 32 years participated in the study on a voluntary basis. All subjects received a ropivacaine injection in 1 of 3 randomized concentrations (2.0, 5.0, or 7.5 mg/mL) for infiltration anesthesia and mandibular nerve block in a double-blind manner. The onset time and duration of anesthesia were assessed by electric pulp test, pinprick test of the gingiva, and presence of feeling of numbness of the lip. RESULTS: Regardless of dose, only 5 patients received pulpal anesthesia after infiltration, but all 3 concentrations anesthetized the gingiva and upper lip. The onset of pulpal anesthesia occurred less than 5 minutes after injection and lasted for 4 to 58 minutes. Pinprick anesthesia lasted for 8 to 48 minutes, and numbness of the upper lip lasted 1 to 4 hours. The effectiveness of the mandibular nerve block with regard to pulpal anesthesia was dose dependent. Only ropivacaine at 7.5 mg/mL produced sufficient anesthesia. The onset of pulpal anesthesia occurred less than 10 minutes after injection and lasted for 2 to 6 hours. Pinprick anesthesia lasted for 3 to 6 hours and numbness of the lower lip lasted for 5 to 9 hours. CONCLUSION: This study shows that ropivacaine could be useful as a local anesthetic for mandibular nerve block in dentistry and that the very long duration of both pulpal and soft tissue anesthesia may be favorable in reducing postoperative pain.

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.

Effect on prostaglandin E2 and leukotriene B4 levels by local administration of glucocorticoid in human masseter muscle myalgia.

Our aim was to determine whether masseter muscle (M) and plasma (P) levels of prostaglandin E2 (PGE2) or leukotriene B4 (LTB4) are influenced by local glucocorticoid administration and whether such changes would be associated with corresponding changes in local pain or hyperalgesia. Eighteen patients with fibromyalgia and 15 with local masseter myalgia were examined immediately before and 2 weeks after intramuscular administration of glucocorticoid with regard to masseter muscle resting pain and tenderness to palpation, pressure pain threshold, maximum voluntary mouth opening (MVM), and pain on maximum voluntary mouth opening. The primary criteria for inclusion were presence of pain for a period of at least 3 months and tenderness to digital palpation in the masseter muscle region. At both visits microdialysis samples were obtained from the masseter muscle, and venous blood was collected for analysis of PGE2 and LTB4. Dialysate levels of M-PGE2 did not change significantly after glucocorticoid administration, but reduction of masseter resting pain and increase of MVM were associated with decrease of M-PGE2 in the patients with fibromyalgia. Dialysate levels of M-LTB4 increased in both groups. In the patients with local myalgia the plasma level of LTB4 also increased, and this increase was associated with a decrease of pain and masseter tenderness. In conclusion, this study shows that reduction of masseter level of PGE2 after intramuscular glucocorticoid administration is associated with a decrease of resting pain in patients with fibromyalgia. In addition, the masseter muscle level of LTB4 increases in patients with fibromyalgia and local myalgia.

Inflammatory mediators and radiographic changes in temporomandibular joints of patients with rheumatoid arthritis.

The aim of this study was to investigate the relation between the inflammatory mediators tumor necrosis factor alpha (TNFalpha) and serotonin (5-HT), the inflammatory markers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), as well as rheumatoid factor (RF) and thrombocyte particle concentration (TPC) in blood versus temporomandibular joint (TMJ) radiographic changes in patients with clinical TMJ involvement by rheumatoid arthritis (RA). Twenty patients were included. Venous blood was collected for quantification of the mediators, markers, and TPC. The radiographic signs of erosion, flattening, sclerosis, subchondral pseudocyst, and osteophyte as well as radiographic grade were investigated with computed tomography. The median (IQR) plasma levels of TNFalpha and 5-HT were 0 (13) pg/ mL and 13 (22) nmol/L, respectively, while serum level of 5-HT was 1360 874) nmol/L ESR, CRP, and TPC were abnormally high in 53%, 250%, and 15% of the patients, respectively. The most frequent radiographic signs were sclerosis (75%), erosion (50%), and flattening (30%). Erosion was found to be associated with high TPC and flattening with high plasma level of TNFalpha. In conclusion, patients with clinical TMJ involvement by RA show an association between high level of TPC and TNFalpha in plasma versus radiographic signs of joint bone destruction.

Impact of temporomandibular joint pain on activities of daily living in patients with rheumatoid arthritis.

The aim of this study was to investigate the impact of temporomandibular joint (TMJ) pain on daily living in patients with rheumatoid arthritis (RA) involving the TMJ. Nineteen patients (17 F, 2 M) with a median (IQR) age of 44 (23) years were included. A scale for the influence of TMJ pain/discomfort on the activities of daily living was used. TMJ resting pain and pain upon maximum mouth opening according to a visual analog scale as well as pressure pain threshold and tenderness to digital palpation of the TMJ were assessed. Blood samples were collected to measure the level of acute phase proteins. Activities of daily living were influenced in all patients at different levels. The impact on daily living by TMJ pain/discomfort was greatest on the performance of physical exercises and jaw movements, while it was smallest on the performance of hobbies and eating. Pain during maximum mouth opening and tenderness to digital palpation were correlated to difficulties with several activities such as to yawn and open the mouth wide, while pressure pain threshold was correlated with difficulties during eating, which confirms that the pain was located in the TMJ. In conclusion, this study indicates that pain/discomfort from the TMJ in patients with RA has a significant negative impact on activities of daily living.