Temporomandibular joint involvement by systemic inflammatory disease with reference to pain modulation and joint tissue destruction

Abstract: Systemic inflammatory diseases may cause progressive destruction in the temporomandibular joint (TMJ). Involvement of this joint is associated with many clinical signs and symptoms of which pain is a major problem. This thesis investigated the relationship between TMJ pain, radiographic changes of the joint, daily activities as well as the influence on TMJ pain and tissue destruction of inflammatory markers and mediators in the blood. Patients with a diagnosis of rheumatoid arthritis (RA) or psoriatic arthritis (PA) and with TMJ clinical involvement were included. The aim of the first study was to investigate the impact of TMJ pain on daily living. A scale for the influence of TMJ pain on the activities of daily living (ADL) was used. ADL was influenced in all patients at different levels, but the impact of pain was most pronounced on the performance of jaw movements and physical exercise. The results indicate that pain from the TMJ in patients with RA has a significant negative impact on activities of daily living. The aim of the second study was to investigate the relation between inflammatory mediators and markers versus presence of TMJ radiographic changes. The most frequent radiographic signs detected by computed tomography (CT) were sclerosis, erosions and flattening. The inflammatory origin of erosion was indicated by its correlation to the thrombocyte particle concentration, while flattening was correlated to plasma concentration of tumor necrosis factor alpha (TNFá). This study thus showed an association between systemic inflammatory activity and radiographic signs of TMJ tissue destruction in patients with clinical TMJ involvement by RA. The aim of the third study was to investigate the longitudinal radiographic changes in the TMJ and their relation to inflammatory mediators and markers in the blood. Regression of erosions was associated with high serum concentration of serotonin (5-HT) and plasma concentration of interleukin-1 soluble receptor type II (IL-1sRII), while progression of erosions was associated with high plasma concentration of 5-HT. Progression of flattening was associated with high C-reactive protein (CRP). 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, but only minor progression can be expected to occur and with considerable individual variation. The aim of the fourth study was to investigate if the 5-HT3 antagonist granisetron reduces TMJ pain. An intra-articular injection of granisetron (1mg) given in a randomized double-blind manner reduced the resting pain in the TMJ according to a visual analogue scale after 10 and 20 minutes. The pain during maximum mouth opening was decreased and pressure pain threshold over the TMJ was increased after 20 min. The latter finding was associated with low level of P-5-HT. Granisetron has an immediate, short-lasting and specific pain reducing effect in TMJ RA or PA and the 5-HT3 receptor therefore seems to be involved in the mediation of TMJ pain in systemic inflammatory joint disorders. This thesis shows that 5-HT is an important mediator of pain and inflammation of the TMJ involved by systemic inflammatory disease and that TNFá and 5-HT are significant mediators of mineralized tissue destruction. Furthermore TMJ pain in patients with RA has a significant nega