{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:18:54Z","timestamp":1792840734487,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["ICI20\/00146"],"award-info":[{"award-number":["ICI20\/00146"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Opioid use disorder (OUD) is a multifaceted condition influenced by sex, genetic and environmental factors that could be linked with epigenetic changes. Understanding how these factors interact is crucial to understand and address the development and progression of this disorder. Our aim was to elucidate different potential epigenetic and genetic mechanisms between women and men that correlate with OUD under real\u2010world pain unit conditions. Associations between analgesic response and the DNA methylation level of the\n                    <jats:italic>opioid mu receptor<\/jats:italic>\n                    (\n                    <jats:italic>OPRM1<\/jats:italic>\n                    ) gene (CpG sites 1\u20135 selected in the promoter region) were evaluated in 345 long opioid\u2010treated chronic non cancer pain: cases with OUD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200967) and controls (without OUD,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009278). Cases showed younger ages, low employment status and quality of life, but higher morphine equivalent daily dose and psychotropic use, compared to the controls. The patients with OUD showed a significant decrease in\n                    <jats:italic>OPRM1<\/jats:italic>\n                    DNA methylation, which correlated with clinical outcomes like pain relief, depression and different adverse events. Significant differences were found at the five CpG sites studied for men, and exclusively in women for CpG site 3, in relation to OUD diagnosis. These findings support the importance of epigenetics and sex as biological variables to be considered toward efficient OUD understanding and therapy development.\n                  <\/jats:p>","DOI":"10.1111\/adb.13422","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T08:00:46Z","timestamp":1719820846000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Epigenetic and sex differences in opioid use disorder in chronic pain: A real\u2010world study linked with\n                    <i>OPRM1<\/i>\n                    DNA methylation"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8739-0456","authenticated-orcid":false,"given":"Laura","family":"Agull\u00f3","sequence":"first","affiliation":[{"name":"Pharmacogenetic Unit, Clinical Pharmacology Department Alicante Institute for Health and Biomedical Research (ISABIAL)  Alicante Spain"},{"name":"Bioengineering Institute, Department of Pharmacology, Paediatrics and Organic Chemistry Miguel Hern\u00e1ndez University (UMH)  Elche Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Escorial","sequence":"additional","affiliation":[{"name":"Pharmacogenetic Unit, Clinical Pharmacology Department Alicante Institute for Health and Biomedical Research (ISABIAL)  Alicante Spain"},{"name":"Bioengineering Institute, Department of Pharmacology, Paediatrics and Organic Chemistry Miguel Hern\u00e1ndez University (UMH)  Elche Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Orut\u00f1o","sequence":"additional","affiliation":[{"name":"Alicante Institute for Health and Biomedical Research (ISABIAL)  Alicante Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Muriel","sequence":"additional","affiliation":[{"name":"Pharmacogenetic Unit, Clinical Pharmacology Department Alicante Institute for Health and Biomedical Research (ISABIAL)  Alicante Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Sandoval","sequence":"additional","affiliation":[{"name":"Epigenomics Unit La Fe Health Research Institute  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Margarit","sequence":"additional","affiliation":[{"name":"Pain Unit, Department of Health of Alicante Dr. Balmis General Hospital  Alicante Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2385-3749","authenticated-orcid":false,"given":"Ana M.","family":"Peir\u00f3","sequence":"additional","affiliation":[{"name":"Pharmacogenetic Unit, Clinical Pharmacology Department Alicante Institute for Health and Biomedical Research (ISABIAL)  Alicante Spain"},{"name":"Bioengineering Institute, Department of Pharmacology, Paediatrics and Organic Chemistry Miguel Hern\u00e1ndez University (UMH)  Elche Spain"},{"name":"Pain Unit, Department of Health of Alicante Dr. Balmis General Hospital  Alicante 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