{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:23:35Z","timestamp":1786116215138,"version":"build-2736575974"},"reference-count":76,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"postgraduate programme Doctorado en Ciencias Silvoagropecuarias y Veterinarias from the Universidad de Chile and ANID programa Beca Doctorado Nacional N","doi-asserted-by":"publisher","award":["21230257\/2023"],"award-info":[{"award-number":["21230257\/2023"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"award":["21230257\/2023"],"award-info":[{"award-number":["21230257\/2023"]}],"id":[{"id":"https:\/\/ror.org\/047gc3g35","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chronic synovial inflammation is a hallmark of osteoarthritis progression and is tightly regulated by synovial macrophages. Recently, voltage-gated sodium channels (NaV) have emerged as potent modulators of macrophage-driven inflammation, positioning them as novel therapeutic targets. Among selective NaV channel blockers, neosaxitoxin exerts remarkable anesthetic and immunomodulatory effects; however, its effects on joint inflammation upon intra-articular delivery remain unexplored. Using an equine model of bilateral carpal osteoarthritis, this study evaluated the immunomodulatory and tissue-preserving effects of intra-articular neosaxitoxin. Sixteen horses were randomized into two experimental groups (n = 8\/each): Neosaxitoxin in one joint and triamcinolone (+control) in the contralateral joint; or neosaxitoxin in one joint and saline (\u2212control) in the contralateral joint. Clinical parameters, synovial fluid cytology and cytokine profiles, and histological changes in synovium and cartilage were assessed over 30 days. Neosaxitoxin reduced synovial inflammation, evidenced by decreased synovial effusion and surface temperature, along with improved joint flexion. Furthermore, synovial fluid from neosaxitoxin-treated joints exhibited lower counts of erythrocytes, neutrophils, total protein, and key pro-inflammatory mediators (IL-1\u03b2 and IL-6) compared to saline-treated controls. Histologically, neosaxitoxin-treated joints exhibited modest synovial inflammatory cell infiltration and minor cartilage abnormalities. In contrast, control joints exhibited synovial hyperplasia, fibrovascular proliferation, and cartilage degeneration. Our data suggests that intra-articular neosaxitoxin better preserved joint homeostasis by limiting synovial inflammation and cartilage damage. These results warrant further investigation on Neosaxitoxin as a candidate treatment for inflammatory arthropathies.<\/jats:p>","DOI":"10.3390\/biom16081142","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T08:08:02Z","timestamp":1786003682000},"page":"1142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neosaxitoxin Downregulates Inflammation in an Equine In Vivo Model of Osteoarthritis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3755-9740","authenticated-orcid":false,"given":"Crist\u00f3bal","family":"D\u00f6rner","sequence":"first","affiliation":[{"name":"Escuela de Medicina Veterinaria, Sede Vi\u00f1a del Mar, Facultad de Ciencias de la Vida, Universidad Andres Bello, Quillota 980, Vi\u00f1a del Mar 2520000, Chile"},{"name":"Programa de Doctorado en Ciencias Silvoagropecuarias y Veterinarias, Campus Sur, Universidad de Chile, Santa Rosa 11315, Santiago 8820808, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00e9stor","family":"Lagos","sequence":"additional","affiliation":[{"name":"Membrane Biochemistry Laboratory, Department of Physiology and Biophysics, Faculty of Medicine, University of Chile, Independencia 1027, Santiago 8380000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lissette","family":"Oyaneder","sequence":"additional","affiliation":[{"name":"Equestria Equine Medical Center, Quillota 2260000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7639-0434","authenticated-orcid":false,"given":"Carlos","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Veterinaria, Sede Santiago, Facultad de Ciencias de la Vida, Universidad Andres Bello, Rep\u00fablica 440, Santiago 8320000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8415-7918","authenticated-orcid":false,"given":"Galia","family":"Ram\u00edrez-Toloza","sequence":"additional","affiliation":[{"name":"Department of Animal Preventive Medicine, Faculty of Veterinary Medicine, University of Chile, Santa Rosa 11735, Santiago 6640022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-4978","authenticated-orcid":false,"given":"Bruno C.","family":"Menarim","sequence":"additional","affiliation":[{"name":"Gluck Equine Research Center, Department of Veterinary Sciences, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40546, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/acr.22721","article-title":"Alternative Methods for Defining Osteoarthritis and the Impact on Estimating Prevalence in a US Population-Based Survey","volume":"68","author":"Cisternas","year":"2016","journal-title":"Arthritis Care Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.15585\/mmwr.mm6620a2","article-title":"Morbidity and Mortality Weekly Report Prevalence of Arthritis and Arthritis-Attributable Activity Limitation by Urban-Rural County Classification-United States, 2015","volume":"66","author":"Boring","year":"2017","journal-title":"MMWR Morb. 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