Objective: To study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes. Methods: OA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA+meloxicam (1.0mg) group was injected intra-articularly in the ACLT knee with 1.0mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA+meloxicam (0.25mg) group was treated similarly with 0.25mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes. Results: OA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA+meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage. Conclusions: Intra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression.
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