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Home / Equine Research Bank / Animals (Basel) / Synovial Fluid Biomarker Profile After Intra-Articular Admin...
Animals : an open access journal from MDPI2025; 15(16); 2453; doi: 10.3390/ani15162453

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

Abstract: 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.
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Publication Date: 2025-08-21 PubMed ID: 40867781PubMed Central: PMC12382866DOI: 10.3390/ani15162453Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study investigated whether injecting neosaxitoxin (NeoSTX), a sodium channel blocker, into horse joints is safe and how it affects inflammation-related markers in joint fluid.
  • The results suggest that NeoSTX injections are well tolerated without causing adverse inflammation in the short term.

Background and Purpose

  • Osteoarthritis (OA) is a common inflammatory joint disease that leads to disability in both humans and animals.
  • A major challenge in OA treatment is finding therapies that reduce inflammation without disrupting the natural balance (homeostasis) of the joint.
  • Voltage-gated sodium (NaV) channels on immune cells called macrophages help regulate inflammation in the synovial membrane of joints.
  • Neosaxitoxin (NeoSTX) is a toxin that blocks NaV channels, potentially controlling inflammation by modulating macrophage activity.
  • The study aimed to evaluate if injecting NeoSTX directly into horse joints is safe and to observe any changes in inflammatory biomarkers in joint fluid.

Study Design and Methods

  • Sixteen healthy horses were divided into two groups of eight animals each.
  • One group received a single injection of 20 μg NeoSTX dissolved in 2 mL saline into one tarsocrural (ankle) joint.
  • The control group received an injection of 2 mL saline only.
  • The horses were monitored for systemic and local signs of inflammation after injection, such as swelling, heat, and joint effusion (fluid buildup).
  • Synovial fluid was sampled and analyzed repeatedly to measure:
    • Cell counts: total nucleated cells and specific immune cell types
    • Biochemical markers: total protein, glucose, calcium levels
    • Concentrations of 23 cytokines and chemokines, which are signaling molecules involved in inflammation

Key Findings

  • No significant differences were found between the NeoSTX and control groups regarding clinical signs such as surface temperature or joint swelling.
  • Synovial fluid analysis showed no differences in cell counts or biochemical markers between treatment groups over the study period.
  • Levels of all measured cytokines and chemokines were similar between NeoSTX-treated and saline-treated joints.
  • These results indicate that intra-articular injection of NeoSTX did not provoke detectable inflammation or toxicity in the short term.

Conclusions and Future Directions

  • NeoSTX appears to be well tolerated when injected into horse joints, with no adverse inflammatory effects observed shortly after administration.
  • The findings support feasibility and safety for using NeoSTX as a potential intra-articular therapy targeting sodium channels to modulate joint inflammation.
  • Further research is needed to:
    • Explore the longer-term effects of NeoSTX on joint health and inflammation control.
    • Understand how NeoSTX influences synovial macrophages and endogenous pathways that resolve inflammation.
    • Evaluate its therapeutic efficacy in models of joint disease such as osteoarthritis.

Cite This Article

APA
Dörner C, Lagos N, Oyaneder L, Menarim BC, Ramírez-Toloza G. (2025). Synovial Fluid Biomarker Profile After Intra-Articular Administration of Neosaxitoxin in Horses: A Feasibility Study. Animals (Basel), 15(16), 2453. https://doi.org/10.3390/ani15162453

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 15
Issue: 16
PII: 2453

Researcher Affiliations

Dörner, Cristóbal
  • Escuela de Medicina Veterinaria, Sede Viña del Mar, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Quillota 980, Viña del Mar 2520000, Chile.
  • Programa de Doctorado en Ciencias Silvoagropecuarias y Veterinarias, Campus Sur Universidad de Chile, Santa Rosa 11315, Santiago 8820808, Chile.
Lagos, Néstor
  • Membrane Biochemistry Laboratory, Department of Physiology and Biophysics, Faculty of Medicine, University of Chile, Independencia 1027, Santiago 8380000, Chile.
Oyaneder, Lissette
  • Equestria Centro Médico Equino, Quillota 2260000, Chile.
Menarim, Bruno C
  • Gluck Equine Research Center, Department of Veterinary Sciences, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Agricultural Science Center North, 1100 S Limestone S107, Lexington, KY 40508, USA.
Ramírez-Toloza, Galia
  • Department of Animal Preventive Medicine, Faculty of Veterinary Medicine, University of Chile, Santa Rosa 11735, Santiago 6640022, Chile.

Grant Funding

  • 21230257/2023 / ANID programa Beca Doctorado Nacional

Conflict of Interest Statement

The authors declare no conflicts of interest.

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