Desenvolvimento de um modelo experimental de artrite reumatoide na articulação temporomandibular : uma análise das alterações morfológicas

Abstract

Rheumatoid arthritis (RA) in temporomandibular joint (TMJ) is an autoimmune synovitis characterized by synovial hyperplasia and erosion of cartilage and subchondral bone. Nociceptive, histopathological and immunological alterations of RA in TMJ are poorly reported in experimental models. Therefore, an experimental model of chronic RA in TMJ was developed using male Wistar rats (180-220 g). These received subcutaneous injections on the back of 200 μl of emulsion containing 500 μg of methylated bovine serum albumin (mBSA) diluted in 100 μl phosphate buffered saline (PBS) and 100 μl of Freund's Complete Adjuvant (CFA) on day 0. On days 7 and 14, the animals received 200 μl of emulsion containing 500 μg of mBSA diluted in 100 μl PBS and 100 μl of IFA on the back. Intra-articular injections in the left TMJ (challenges) with solution of mBSA and PBS (10 μg / joint) were performed on days 21, 28 and 35. Hypernociception analysis was performed throughout the induction period of RA through the Von Frey electronic. The animals were euthanized 7 days after the first challenge, and 24 hours and 7 days after the second and third challenges. TMJs and their peri-articular tissues were removed for histopathological and immunohistochemical for TNFα, IL-1β and IL-6 analysis. Synovial fluid was extracted for the total cell count and for quantification of TNF-α and IL-1β. Nociceptive threshold reduction was observed during the entire experimental groups receiving mBSA at TMJ (p <0.05). The groups euthanized 24 hours after 2 and 3 challenges presented an intense inflammatory infiltrate predominantly mononuclear in the synovial membrane and in the periarticular tissue (p <0.05), increase of joint disc thickness and pannus formation. In the immunohistochemical analysis, these same groups had increased IL- 1β immunostaining in synoviocytes and articular cartilage, IL-6 only in the articular cartilage and TNF-α in synoviocytes, cartilage and synovial membrane (p <0.05). There was a significant increase in IL-1β quantification and total cell count only in the group with 3 challenges and 24-hour euthanasia, and TNF-α quantification in the groups euthanized 24 hours after 2 and 3 challenges (p <0.05). Therefore, the results suggest that this model reproduces morphological alterations evidenced in the TMJ of patients with RA.