{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T14:51:28Z","timestamp":1774882288083,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,29]],"date-time":"2019-12-29T00:00:00Z","timestamp":1577577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades, Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER), Uni\u00f3n Europea","award":["PI1800645"],"award-info":[{"award-number":["PI1800645"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Osteoarthritis and its associated comorbidities are important clinical problems that have a negative impact on the quality of life, and its treatment remains unresolved. We investigated whether the systemic administration of slow-releasing hydrogen sulfide (H2S) donors, allyl isothiocyanate (A-ITC) and phenyl isothiocyanate (P-ITC), alleviates chronic osteoarthritis pain and the associated emotional disorders. In C57BL\/6 female mice with osteoarthritis pain induced by the intra-articular injection of monosodium iodoacetate, we evaluated the effects of repeated administration of A-ITC and P-ITC on the (i) mechanical allodynia and grip strength deficits; (ii) emotional conducts; and (iii) glial activity and expression of inducible nitric oxide synthase (NOS2), phosphatidylinositol 3-kinase (PI3K)\/protein kinase B (Akt), and antioxidant enzymes (heme oxygenase 1, NAD(P)H:quinone oxidoreductase-1, glutathione S-transferase mu 1 and alpha 1) in the hippocampus. The administration of A-ITC and P-ITC inhibited the mechanical allodynia, the grip strength deficits, and the depressive-like behaviors accompanying osteoarthritis. Both treatments inhibited microglial activation, normalized the upregulation of NOS2 and PI3K\/p-Akt, and maintained high levels of antioxidant\/detoxificant enzymes in the hippocampus. Data suggest that treatment with low doses of slow-releasing H2S donors might be an interesting strategy for the treatment of nociception, functional disability, and emotional disorders associated with osteoarthritis pain.<\/jats:p>","DOI":"10.3390\/antiox9010031","type":"journal-article","created":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T05:49:41Z","timestamp":1577684981000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The Inhibitory Effects of Slow-Releasing Hydrogen Sulfide Donors in the Mechanical Allodynia, Grip Strength Deficits, and Depressive-Like Behaviors Associated with Chronic Osteoarthritis Pain"],"prefix":"10.3390","volume":"9","author":[{"given":"Gerard","family":"Batall\u00e9","sequence":"first","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Cabarga","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4621-8457","authenticated-orcid":false,"given":"Olga","family":"Pol","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.bcp.2010.02.017","article-title":"New molecular targets for the treatment of osteoarthritis","volume":"80","author":"Alcaraz","year":"2010","journal-title":"Biochem. 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