leukotriene-b4 and Temporomandibular-Joint-Disorders

Orofacial pain frequently originates from pathologic conditions in the masticatory muscles or temporomandibular joints (TMJs). The mediators and mechanisms that monitor pain and inflammation, centrally or peripherally, are of great interest in the search for new treatment modalities. The neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) have all been found at high levels in the synovial fluid of arthritic TMJs in association with spontaneous pain, while serotonin (5-HT) has been found in association with hyperalgesia/allodynia of the TMJ. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) have been found in arthritic TMJs, but not in healthy TMJs, in association with hyperalgesia/allodynia of the TMJ as well as spontaneous pain. Anterior open bite, which may be a clinical sign of TMJ destruction, has been found in association with high levels of CGRP, NPY, and IL-1 beta in the synovial fluid of the TMJ. Interleukin-1 beta has also been related to radiographic signs of joint destruction. Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are both present in the arthritic TMJ, and PGE2 has been shown to be associated with hyperalgesia/allodynia of the TMJ. Very little is known about pain and inflammatory mediators in muscles. However, we know that 5-HT and PGE2 are involved in the development of pain and hyperalgesia/allodynia of the masseter muscle in patients with fibromyalgia, whereas local myalgia (myofascial pain) seems to be modulated by other, as yet unknown mediators. Interaction between the peripheral nervous system (sensory and sympathetic nerves), the immune system, and local cells is probably of great importance for the modulation of pain and inflammation in the TMJ and orofacial musculature.

Topics: Arthritis; Calcitonin Gene-Related Peptide; Dinoprostone; Facial Pain; Fibromyalgia; Humans; Hyperalgesia; Inflammation Mediators; Interleukin-1; Leukotriene B4; Masseter Muscle; Neuroimmunomodulation; Neuropeptide Y; Neuropeptides; Neurosecretory Systems; Open Bite; Serotonin; Substance P; Synovial Fluid; Temporomandibular Joint Disorders; Tumor Necrosis Factor-alpha

Facial trauma has been suggested as a possible etiologic factor of temporomandibular joint disorder. However, there is little information on the role of macrotrauma. The main purpose of this study was to validate facial trauma as a potential etiologic factor for temporomandibular joint (TMJ) disorder. Multidirectional approaches were applied for the evaluation of the changes of TMJ after TMJ macrotrauma.. Analysis of TMJ status including arthroscopic examination, histomorphologic examination, and synovial fluid biochemical analysis were performed on the patients with mandibular fractures. Additionally, the efficacy of arthrocentesis for the patients of mandibular fracture was evaluated from the functional point of view.. In arthroscopic examinations, evidence of synovitis with variable degrees was found. The representative findings are fibrillation and ecchymosis. On histomorphologic examination, bloody smear, degenerated cells and cartilage, inflammatory cells, and crystal were observed. In biochemical analysis, considerable amounts of prostaglandin E(2) and leukotriene B(4) were detected in the synovial fluid of the patients.. The inflammatory and degenerative changes of TMJ can develop after facial trauma. Trauma can be a possible etiologic factor in cartilage degeneration, and biochemical and intra-articular pathology. Clinicians should recognize the etiologic importance of macrotrauma, and long-term evaluation of the TMJ as well as adequate treatment is required for patients with facial trauma.

Topics: Dinoprostone; Facial Injuries; Humans; Leukotriene B4; Mandibular Fractures; Paracentesis; Synovial Fluid; Synovitis; Temporomandibular Joint; Temporomandibular Joint Disorders

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.

Topics: Animals; Arachidonate 5-Lipoxygenase; Benzopyrans; Carboxylic Acids; Cell Movement; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Indoles; Leukotriene B4; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Temporomandibular Joint; Temporomandibular Joint Disorders; Time Factors; Zymosan

To compare levels of bradykinin (BK), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and substance P (SP) between successful and unsuccessful cases of arthrocentesis of temporomandibular joint disorders (TMDs).. A total of 66 joints in 66 patients with TMDs who underwent arthrocentesis were evaluated in this study. Synovial fluid diluted with saline solution was aspirated from the superior joint compartment before arthrocentesis and their concentrations of BK, LTB4, PGE2, and SP were determined by enzyme-linked immunosorbent assay. The differences in the detection rate and concentration of each mediator between successful cases and unsuccessful cases of arthrocentesis were analyzed statistically.. Arthrocentesis was successful for 77% (51/66) of the joints. The mean detection rate of LTB4 was significantly (P < .05) higher in the unsuccessful cases (47%) than in the successful cases (16%). The mean concentration of BK was significantly (P < .0005) higher in the unsuccessful cases (425 pg/mL) than in the successful cases (144 pg/mL). There was also a statistical correlation between the detection of LTB4 and PGE2 (P < .01).. Increased levels of BK and LTB4 in the synovial fluid of patients with TMDs may indicate that arthrocentesis is less likely to be a successful treatment.

Topics: Adolescent; Adult; Aged; Bradykinin; Dinoprostone; Female; Humans; Joint Dislocations; Leukotriene B4; Male; Middle Aged; Osteoarthritis; Pain; Paracentesis; Prognosis; Statistics, Nonparametric; Substance P; Synovial Fluid; Temporomandibular Joint Disorders

The relation between disease severity and the known mediators of pain, inflammation, and tissue damage-prostaglandin E 2 (PGE 2 ), leukotriene B 4 (LTB 4 ), malondialdehyde (MDA), nitric oxide (NO), and myeloperoxidase (MPO)-was examined in the synovial fluid of patients with internal derangement (ID) of the temporomandibular joint (TMJ).. Thirty-two patients with ID were classified according to Wilkes by clinical and radiological examinations, and TMJ synovial fluid samples were obtained by arthrocentesis. PGE 2 and LTB 4 levels were measured by ELISA kits, MDA levels were determined by a fluorometric method, myeloperoxidase activity was determined by an end-point method, and NO levels were measured by Griess reaction.. The earliest significant increase was observed in NO levels (stage II) and this elevation persisted in the subsequent stages. The first significant elevation in PGE 2 and LTB 4 levels and MPO activity were observed in stage III. Both PGE 2 and LTB 4 levels were increased in stage III and were correlated with each at this stage and in the subsequent stage. Significant increases in MDA levels were observed only in stage IV. At stage IV there was correlation between MDA and PGE 2 , MDA and LTB 4 , and MDA and MPO. The relation between PGE 2 and MDA was the most powerful one.. Results of this cross-sectional study point out the relation between disease severity and levels of some molecular mediators in synovial fluid of TMJ. Longitudinal studies are needed to explore the role of these molecular mediators in the progression of ID.

Topics: Adolescent; Adult; Cross-Sectional Studies; Dinoprostone; Facial Pain; Female; Humans; Inflammation Mediators; Joint Dislocations; Leukotriene B4; Male; Malondialdehyde; Middle Aged; Nitric Oxide; Peroxidase; Synovial Fluid; Temporomandibular Joint Disorders

The purpose of this study was to investigate the correlations between the concentrations of pain-related mediators in synovial fluid and the degree of synovitis and between the concentrations of pain-related mediators and the degree of joint pain in patients with internal derangement and osteoarthritis of the temporomandibular joint.. The concentrations of substance P, serotonin, bradykinin, leukotriene B(4) (LTB(4)), and prostaglandin E(2) in SF and the degree of arthroscopic synovitis of 32 joints with internal derangement and osteoarthritis were assessed. The correlations between the concentration of each mediator and the score of arthroscopic synovitis and between the concentration of each mediator and the score of joint pain were analyzed statistically.. The detection rates of substance P, serotonin, bradykinin, LTB(4), and prostaglandin E(2) were 25%, 25%, 91%, 53%, and 16%, respectively. Positive correlations were found between the concentrations of bradykinin and LTB(4) and the score of synovitis.. Bradykinin in SF might be useful as an index of the degree of synovitis.

Topics: Adolescent; Adult; Aged; Arthralgia; Bradykinin; Dinoprostone; Enzyme-Linked Immunosorbent Assay; Facial Pain; Female; Humans; Inflammation Mediators; Joint Dislocations; Leukotriene B4; Male; Middle Aged; Neurotransmitter Agents; Nociceptors; Osteoarthritis; Serotonin; Statistics, Nonparametric; Substance P; Synovial Fluid; Synovitis; Temporomandibular Joint Disorders