Inflammation and Fibrosis Induced by Joint Remobilization, and Relevance to Progression of Arthrogenic Joint...

Joint immobilization is frequently administered after fractures and ligament injuries and can cause joint contracture as a side effect. The structures responsible for immobilization-induced joint contracture can be roughly divided into muscular and articular. During remobilization, although myogenic contracture recovers spontaneously, arthrogenic contracture is irreversible or deteriorates further. Immediately after remobilization, an inflammatory response is observed, characterized by joint swelling, deposit formation in the joint space, edema, inflammatory cell infiltration, and the upregulation of genes encoding proinflammatory cytokines in the joint capsule. Subsequently, fibrosis in the joint capsule develops, in parallel with progressing arthrogenic contracture. The triggers of remobilization-induced joint inflammation are not fully understood, but two potential mechanisms are proposed: 1) micro-damage induced by mechanical stress in the joint capsule, and 2) nitric oxide (NO) production via NO synthase 2. Some interventions can modulate remobilization-induced inflammatory and subsequent fibrotic reactions. Anti-inflammatory treatments, such as steroidal anti-inflammatory drugs and low-level laser therapy, can attenuate joint capsule fibrosis and the progression of arthrogenic contracture in remobilized joints. Antiproliferative treatment using the cell-proliferation inhibitor mitomycin C can also attenuate joint capsule fibrosis by inhibiting fibroblast proliferation without suppressing inflammation. Conversely, aggressive exercise during the early remobilization phases is counterproductive, because it facilitates inflammatory and then fibrotic reactions in the joint. However, the adverse effects of aggressive exercise on remobilization-induced inflammation and fibrosis are offset by anti-inflammatory treatment. To prevent the progression of arthrogenic contracture during remobilization, therefore, care should be taken to control inflammatory and fibrotic reactions in the joints.