Evaluation of the Antifibrotic and Functional Effects of Pirfenidone in an Experimental Frozen Shoulder Model

This study aimed to investigate the histopathological and functional effects of pirfenidone in a rat model of frozen shoulder (adhesive capsulitis). Thirty-two male Wistar Albino rats were randomly divided into four groups (n = 8 each): control, frozen shoulder (FS), pirfenidone-treated (FS + PFD), and dexamethasone-treated (FS + DEX). The FS model was induced by immobilizing the shoulder joint with plaster for 4 weeks. Treatment groups received oral pirfenidone (30 mg/kg/day) or prednisolone (3 mg/kg/day) for 30 days. Histopathological changes in the synovial membrane and fibrous capsule were evaluated with hematoxylin-eosin and Masson's trichrome staining, while shoulder joint range of motion (ROM) was measured. The FS group showed significant pathological alterations, including synovial epithelial atrophy, loss of synovial folds, hyperemia, edema, and severe capsular fibrosis. Both pirfenidone and dexamethasone treatments reduced these abnormalities. Pirfenidone was more effective in preserving collagen fiber organization and synovial fold integrity. ROM was markedly reduced in the FS group, but partial recovery occurred in both treatment groups. Pirfenidone provided greater functional improvement compared with dexamethasone. Inflammation scores did not differ significantly between groups, consistent with evaluation during the fibrotic phase. Pirfenidone attenuates fibrotic changes and improves joint mobility in an experimental frozen shoulder model. Pirfenidone improved histological fibrosis scores and ROM in this experimental model. Comparative effectiveness versus corticosteroids requires confirmation in larger, appropriately powered studies. These results emphasize the antifibrotic potential of pirfenidone and support further long-term and clinical studies to clarify its role in adhesive capsulitis management.