EXPERIMENTAL MODEL OF RHEUMATOID ARTHRITIS IN TEMPOROMANDIBULAR JOINT: AN UPDATE
Authors: da Silveira Helson Freitas , de Sousa Luane Macêdo , dos Santos Alves Joana Maria , de Melo Nunes Rodolfo , da Silva Martins Conceição , Goes Paula , Gondim Delane Viana 
Published: June 2021

Rheumatoid arthritis (RA) is a systemic and progressive inflammatory disease characterized by synovial inflammation and hyperplasia, production of autoantibodies and destruction of cartilage and bone. The etiology of RA has yet to be elucidated and numerous joints have shown limited functions. It is estimated that 65% of patients with this disease have symptoms in the temporomandibular joint (TMJ), but the nociceptive, histopathological and immunological alterations of RA in this joint are poorly reported. Experimental models are essential in order to better understand the pathological mechanisms underlying the tissue breakdown and the development of new therapeutic approaches. Actually, the experimental model of RA in TMJ is induced by one injection of methylated bovine serum albumin (mBSA) to reproduced acute phase of RA. Thus, the aim of this study was to update an experimental model of chronic RA with booster injections of mBSA and evalute the morphological alterations in TMJ. 24 male Wistar rats (180 – 220g), originating from the Central Animal Facility of the Federal University of Ceará – Brazil, kept at 22°C, by day/night cicle – 12/12 h, with water and food ad libitum. Initially, the animals were sensitized with an emulsion containing methylated mBSA and Complete Freund Adjuvant (CFA), subcutaneously administered. Booster injections of mBSA dissolved in Incomplete Freund Adjuvant (IFA) were administered 7 and 14 days after the first immunization. 21 days after initial injections, arthritis in the left TMJ was induced in immunized animals by an intra‐articular injection of mBSA (10 μg/i.art.). Booster injections of mBSA were given on days 28 and 35. The animals were euthanized 24 h after each mBSA injection in the left TMJ. The Control group did not receive intra‐articular mBSA injections. The animals that received 1, 2 or 3 mBSA injections in the left TMJ, received saline (0,9%; 10 μl; i.art) in the right TMJ. The animals were divided in 4 groups (n=6): control, mBSA (1), mBSA (2), mBSA (3). Nociceptive threshold was performed during the whole experiment using an analgesymeter. After 24h of mBSA injections, synovial fluid was extracted for a total cell count and TMJs were removed for histopathological and immunohistochemical analysis for IL‐1β, IL‐6 and TNF‐α. The mechanical allodynia evaluation in the left TMJ showed that, during the subcutaneous administration of mBSA, there was no alteration on the nociceptive threshold in the TMJ (FIGURE 1A). But, during mBSA intra‐articular injection, a significant reduction of nociceptive threshold was observed (p =0.000) (FIGURE 1B). The saline administered in the right TMJ of rats that received 1, 2 or 3 injections of mBSA in the left TMJ showed no statistical difference compared to the control group. The mBSA (2) and mBSA (3) groups showed an intense mononuclear inflammatory infiltrate, thickening of the articular disc, but only the group that received 3 mBSA injections showed extensive joint destruction and an increase of cellular influx (FIGURE 1C AND 1D). In the immunohistochemistry, IL‐1β, IL‐6 and TNF‐α expression were increased in the synoviocytes layer, joint cartilage and synovial membrane in the groups that received 2 and 3 mBSA injections in TMJ (p <0.05) (FIGURE 2A, 2B AND 2C). In conclusion, this new experimental approach simulates the chronic RA in TMJ because shows nociceptive, histopathological and immunological clinical findings similar to human RA.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.