{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:21:55Z","timestamp":1782976915342,"version":"3.54.5"},"reference-count":66,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"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)","award":["PI18\/00645"],"award-info":[{"award-number":["PI18\/00645"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades, Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER)","award":["PI21\/00592"],"award-info":[{"award-number":["PI21\/00592"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The pain-relieving properties of opioids in inflammatory and neuropathic pain are heightened by hydrogen sulfide (H2S). However, whether allodynia and functional and\/or emotional impairments related to osteoarthritis (OA) could be reduced by activating \u03b4-opioid receptors (DOR) and the plausible influence of H2S on these actions has not been completely established. In female C57BL\/6J mice with OA pain generated via monosodium acetate (MIA), we analyze: (i) the effects of UFP-512 (a DOR agonist), given alone and co-administered with two H2S donors, on the symptoms of allodynia, loss of grip strength (GS), and anxiodepressive-like comportment; (ii) the reversion of UFP-512 actions with naltrindole (a DOR antagonist), and (iii) the impact of UFP-512 on the expression of phosphorylated NF-kB inhibitor alpha (p-IKB\u03b1) and the antioxidant enzymes superoxide dismutase 1 (SOD-1) and glutathione sulfur transferase M1 (GSTM1); and the effects of H2S on DOR levels in the dorsal root ganglia (DRG), amygdala (AMG), and hippocampus (HIP) of MIA-injected animals. Results showed that systemic and local administration of UFP-512 dose-dependently diminished the allodynia and loss of GS caused by MIA, whose effects were potentiated by H2S and reversed by naltrindole. UFP-512 also inhibited anxiodepressive-like behaviors, normalized the overexpression of p-IKB\u03b1 in DRG and HIP, and enhanced the expression of SOD-1 and GSTM1 in DRG, HIP, and\/or AMG. Moreover, the increased expression of DOR triggered by H2S might support the improved analgesic actions of UFP-512 co-administered with H2S donors. This study proposes the use of DOR agonists, alone or combined with H2S donors, as a new treatment for OA pain.<\/jats:p>","DOI":"10.3390\/antiox12122085","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T03:35:31Z","timestamp":1701920131000},"page":"2085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Impact of UFP-512 in Mice with Osteoarthritis Pain: The Role of Hydrogen Sulfide"],"prefix":"10.3390","volume":"12","author":[{"given":"Gerard","family":"Batall\u00e9","sequence":"first","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut de Recerca Sant Pau, 08041 Barcelona, Spain"},{"name":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7283-3189","authenticated-orcid":false,"given":"Xue","family":"Bai","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut de Recerca Sant Pau, 08041 Barcelona, Spain"},{"name":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4437-6096","authenticated-orcid":false,"given":"Gianfranco","family":"Balboni","sequence":"additional","affiliation":[{"name":"Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, Department of Life and Environmental Sciences, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4621-8457","authenticated-orcid":false,"given":"Olga","family":"Pol","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut de Recerca Sant Pau, 08041 Barcelona, Spain"},{"name":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41584-018-0001-0","article-title":"Mitochondrial DNA variation and the pathogenesis of osteoarthritis phenotypes","volume":"14","author":"Blanco","year":"2018","journal-title":"Nat. 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