Intra-articular magnesium sulfate (MgSO₄) reduces experimental osteoarthritis and nociception: association with attenuation of N-methyl-d-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes

Objective: To study the effects of intra-articular injection of magnesium sulfate (MgSO₄) on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. Methods: OA was induced in Wistar rats with intra-articular injection of collagenase (500 U) in the right knee; the left knee was left untreated. In the OA + MgSO₄ group (n = 7), the treated knee was injected with 500-μg (0.1-ml) MgSO₄ twice a week for 5 consecutive weeks starting at 1 week after collagenase injection; in the OA group (n = 7), the same knee was injected with the same amount of physiological normal saline. In the MgSO₄ group (n = 6), naïve rats received only MgSO₄ injections; in the control group (n = 6), naïve rats received only physiological normal saline injections. Nociceptive behavior (mechanical allodynia and thermal hyperalgesia) on OA development was measured before and at 1, 2, 4, 6, and 8 weeks after collagenase injection, following which the animals were sacrificed. Gross morphology and histopathology were examined in the femoral condyles, tibial plateau, and synovia. Immunohistochemical analysis was performed to examine the effect of MgSO₄ on N-methyl-d-aspartate (NMDA) receptor subunit 1 phosphorylation (p-NR1) and apoptosis in the articular cartilage chondrocytes. Results: OA rats receiving intra-articular MgSO₄ injections showed a significantly lower degree of cartilage degeneration than the rats receiving saline injections. MgSO₄ treatment also suppressed synovitis. Mechanical allodynia and thermal hyperalgesia showed significant improvement in the OA + MgSO₄ group as compared to the OA group. Moreover, MgSO₄ attenuated p-NR1 and chondrocyte apoptosis in OA-affected cartilage. Conclusions: Our results indicate that local intra-articular administration of MgSO₄ following collagenase injection in an experimental rat OA model (1) modulates chondrocyte metabolism through inhibition of cell NMDA receptor phosphorylation and apoptosis, (2) attenuates the development of OA, and (3) concomitantly reduces nociception. Crown