{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T14:51:29Z","timestamp":1774882289836,"version":"3.50.1"},"reference-count":85,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia","award":["PI18\/00645"],"award-info":[{"award-number":["PI18\/00645"]}]},{"name":"Ministerio de Ciencia","award":["PI21\/00592"],"award-info":[{"award-number":["PI21\/00592"]}]},{"name":"Innovaci\u00f3n y Universidades","award":["PI18\/00645"],"award-info":[{"award-number":["PI18\/00645"]}]},{"name":"Innovaci\u00f3n y Universidades","award":["PI21\/00592"],"award-info":[{"award-number":["PI21\/00592"]}]},{"name":"Instituto de Salud Carlos III","award":["PI18\/00645"],"award-info":[{"award-number":["PI18\/00645"]}]},{"name":"Instituto de Salud Carlos III","award":["PI21\/00592"],"award-info":[{"award-number":["PI21\/00592"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["PI18\/00645"],"award-info":[{"award-number":["PI18\/00645"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["PI21\/00592"],"award-info":[{"award-number":["PI21\/00592"]}]},{"name":"Uni\u00f3n Europea","award":["PI18\/00645"],"award-info":[{"award-number":["PI18\/00645"]}]},{"name":"Uni\u00f3n Europea","award":["PI21\/00592"],"award-info":[{"award-number":["PI21\/00592"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Hydrogen sulfide (H2S) donors make opioids more effective in inhibiting nociception during inflammatory and neuropathic pain. We examined whether the analgesic, anxiolytic and\/or antidepressant actions of the cannabinoid 2 receptor (CB2R) agonist, JWH-133, might be improved by pretreatment with H2S donors, DADS and GYY4137 in mice with sciatic nerve injury-provoked neuropathy (CCI). The reversion of the antinociceptive effects of these treatments with the CB2R antagonist, AM630, and the regulatory actions of H2S in the phosphorylation of NF-\u03baB inhibitor alpha (IKB\u03b1) and in the brain-derived neurotrophic factor (BDNF), CB2R, Nrf2 and heme oxygenase 1 (HO-1) levels in prefrontal cortex (PFC), ventral hippocampus (vHIP) and periaqueductal gray matter (PAG), were examined. Data showed that the analgesic effects of JWH-133, systemically and locally administered, were improved by the DADS or GYY4137 pretreatment. The co-treatment of GYY4137 with JWH-133 also stopped anxiodepressive-like activities that concur with neuropathy. Our data likewise showed that both H2S donors normalized the inflammatory (p-IKB\u03b1), neurotrophic (BDNF) variations caused by CCI, increased the expression of CB2R and activated the Nrf2\/HO-1 antioxidant pathway in PFC, v-HIP and\/or PAG of animals with neuropathic pain. In addition, the blockade of the analgesia produced by high doses of DADS and GYY4137 with AM630 indicated the contribution of the endocannabinoid system in the effects of H2S during neuropathic pain, thus supporting the positive interaction between H2S and CB2R. Therefore, this study demonstrates the potential use of CB2R agonists combined with H2S donors as a possible treatment for peripheral nerve injury-caused neuropathic pain and the associated emotional disturbances.<\/jats:p>","DOI":"10.3390\/antiox12061179","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T03:02:23Z","timestamp":1685415743000},"page":"1179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hydrogen Sulfide Interacting with Cannabinoid 2 Receptors during Sciatic Nerve Injury-Induced Neuropathic Pain"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7283-3189","authenticated-orcid":false,"given":"Xue","family":"Bai","sequence":"first","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB 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":"Batall\u00e9","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB 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":"Ignacio","family":"Mart\u00ednez-Martel","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB 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 (IIB 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":[[2023,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3109\/00207454.2012.746335","article-title":"Neuropathic pain, depressive symptoms, and C-reactive protein in sciatica patients","volume":"123","author":"Uher","year":"2013","journal-title":"Int. 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