{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T14:51:55Z","timestamp":1774882315229,"version":"3.50.1"},"reference-count":69,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,16]],"date-time":"2021-10-16T00:00:00Z","timestamp":1634342400000},"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>Chronic osteoarthritis pain is accompanied by several comorbidities whose treatment has not been completely resolved. The anti-inflammatory, analgesic, and antidepressant effects of slow-releasing hydrogen sulfide (H2S) donors during osteoarthritic pain have been shown, but their actions in the accompanying memory impairment and anxious-like behaviors have not yet been demonstrated. Using female mice with chronic osteoarthritic pain, the effects of natural, diallyl disulfide (DADS) or synthetic, morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137) slow-releasing H2S donors, on associated cognitive and grip strength deficits and anxiodepressive-like behaviors, were assessed. Their effects on specific brain areas implicated in the modulation of pain and emotional responses were also determined. Results demonstrated an improvement in memory and grip strength deficits, as well as in the anxious-like behaviors associated with chronic pain in GYY4137 and\/or DADS treated mice. The painkiller and antidepressant properties of both treatments were also established. Treatment with DADS and\/or GYY4137 inhibited: oxidative stress in the amygdala; phosphoinositide 3-kinase overexpression in the amygdala, periaqueductal gray matter, and anterior cingulate cortex; protein kinase B activation in the amygdala and infralimbic cortex; up-regulation of inducible nitric oxide synthase in the amygdala, periaqueductal gray matter and infralimbic cortex and apoptotic responses in the amygdala. These results might explain the recovery of memory and grip strength and the inhibition of allodynia and associated anxiodepressive-like behaviors by these treatments. In conclusion, this study revealed new properties of slow-releasing H2S donors in cognitive impairment and affective disorders linked with chronic osteoarthritis pain and their effects on the central nervous system.<\/jats:p>","DOI":"10.3390\/antiox10101632","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T23:13:32Z","timestamp":1634512412000},"page":"1632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Recovery of Cognitive and Affective Deficiencies Linked with Chronic Osteoarthritis Pain and Implicated Pathways by Slow-Releasing Hydrogen Sulfide Treatment"],"prefix":"10.3390","volume":"10","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":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7283-3189","authenticated-orcid":false,"given":"Xue","family":"Bai","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":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enric","family":"Pouso-V\u00e1zquez","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":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard","family":"Roch","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":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Rodr\u00edguez","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":"Grup de Neurofarmacologia Molecular, 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":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","article-title":"OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis","volume":"27","author":"Bannuru","year":"2019","journal-title":"Osteoarthr. 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