Dissociation Between Functional Performance and Structural Joint Damage Following Sertraline Treatment in Collagen-Induced Arthritis

Rheumatoid arthritis is a chronic inflammatory joint disease often accompanied by depressive symptoms, in which functional impairment does not always reflect the extent of structural joint damage. Sertraline, a selective serotonin reuptake inhibitor, may influence behavioural and neuroimmune pathways, but its effects on the relationship between joint pathology and functional performance remain unclear. This study evaluated whether sertraline affects functional performance independently of histopathological joint damage in collagen-induced arthritis. Male Wistar rats with collagen-induced arthritis were assigned to untreated or treatment groups receiving sertraline, methotrexate, combined methotrexate and sertraline, infliximab, or tocilizumab. Functional performance was assessed by spontaneous wheel-running activity, body weight, and joint swelling. At week 12, ankle joints underwent histopathological evaluation, and haematological parameters and serum cytokines were analysed. Sertraline did not reduce synovial inflammation, cartilage damage, or bone erosion, although sertraline-treated rats showed a smaller numerical decline in spontaneous wheel-running activity than rats with untreated collagen-induced arthritis. In contrast, methotrexate and biologic therapies improved both structural damage and functional outcomes. Functional performance did not consistently correlate with histopathological severity or circulating cytokine levels. Sertraline did not produce a significant improvement in histopathological outcomes compared with untreated collagen-induced arthritis, while the smaller numerical decline in exploratory wheel-running activity should be interpreted cautiously.