Synovial Fluid Biomarker Profile After Intra-Articular Administration of Neosaxitoxin in Horses: A Feasibility Study

Osteoarthritis (OA) is an inflammatory joint disease and the leading cause of musculoskeletal disability affecting human and veterinary patients. New therapeutics halting inflammation while preserving joint homeostasis remain a critical need. Voltage-gated sodium (NaV) channels regulate the pro-inflammatory response of macrophages in the synovium, the central driver of joint homeostasis. Neosaxitoxin (NeoSTX) is a phycotoxin that blocks NaV channels, conferring a unique potential to regulate joint inflammation. This study evaluated the safety of intra-articular administration of NeoSTX in horses. Sixteen horses were allocated into two groups (n = 8/each). One group received one intraarticular dose (20 µg/2 mL of saline) of NeoSTX into one tarsocrural joint, while the control group received 2 mL of saline (0.9% NaCl). No differences were observed between groups for systemic or local signs of inflammation, including objective measures of surface temperature and joint effusion. Concentrations of synovial fluid total nucleated and differential cell counts, total protein, glucose, calcium, and 23 cytokines/chemokines measured throughout this study did not differ between treatment groups. In this short-term study, intra-articular NeoSTX injection was shown to be well tolerated and likely safe. Ongoing studies should elucidate the role of NeoSTX in modulating synovial mechanisms of inflammation and its endogenous resolution.