Effects of methotrexate on Wnt/β-catenin signaling and glial activation in temporomandibular joint arthritis in rats.

Abstract

Rheumatoid arthritis is a chronic autoimmune disease that can affect the temporomandibular joint (TMJ) and cause pain. Methotrexate is widely used to control disease progression, but its effects on pain mechanisms are not fully understood. This study evaluated the antinociceptive effects of methotrexate on pain behavior, Wnt/β-catenin pathway expression, and glial activation in the trigeminal nociceptive pathway in rats with TMJ arthritis. Eighteen male Wistar rats were assigned to one of three groups: control, arthritic, or arthritic treated with methotrexate. Arthritis was induced by intra-articular injection of methylated bovine serum albumin. Pain behavior, inflammation, and joint damage were assessed. Immunoexpression of Wnt/β-catenin components and c-Fos was analyzed in the trigeminal ganglion and subnucleus caudalis, along with microglial activation. Methotrexate-treated arthritic rats showed increased pain threshold, reduced facial pain behaviors, and decreased inflammatory infiltrates, along with lower levels of tumor necrosis factor-α and interleukin-17 in the joint compared to untreated arthritic rats. Methotrexate also reduced c-Fos, Wnt-10b, β-catenin, and glutamine synthetase expression in the trigeminal ganglion and attenuated microglial activation in the subnucleus caudalis. These results indicate that methotrexate produces antinociceptive effects by modulating Wnt/β-catenin signaling and reducing glial activation in the trigeminal nociceptive pathway in rats with TMJ arthritis.