{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:08:45Z","timestamp":1787069325156,"version":"build-2736575974"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171205 81801107 81571077"],"award-info":[{"award-number":["82171205 81801107 81571077"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Intraoperative remifentanil infusion may paradoxically induce post-surgical hyperalgesia. Dexmedetomidine reportedly reduces opioid-induced hyperalgesia. Nalmefene selectively reverses several side-effects of opioids without impairing analgesia. Herein, this randomized, double-blind controlled trial investigated whether nalmefene, dexmedetomidine, and both drugs combined prevent remifentanil-induced hyperalgesia. One hundred and fifty patients undergoing elective laparoscopic gynecological surgery under desflurane anesthesia randomly received either intraoperative sufentanil 0.20\u00a0\u03bcg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    (Group S), or remifentanil 0.20\u00a0\u03bcg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00a0min\n                    <jats:sup>\u22121<\/jats:sup>\n                    (Group R), or remifentanil and pre-anesthesia nalmefene 0.20\u00a0\u03bcg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    (Group N), or remifentanil and pre-anesthesia dexmedetomidine 0.50\u00a0\u03bcg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    (Group D), or remifentanil and the combination of dexmedetomidine 0.25\u00a0\u03bcg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    and nalmefene 0.10\u00a0\u03bcg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    (Group DN). The threshold of postoperative mechanical hyperalgesia (primary outcome) was measured with von Frey filaments. We also recorded pain intensity, analgesic consumptions, hyperalgesic area, and side-effects for 24\u00a0h postoperatively. Compared with Group S, remifentanil reduced hyperalgesic threshold on the forearm [mean 89.4 (SD 13.7) vs. 62.2 (10.7) g,\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.001] at postoperative 24\u00a0h. Pain threshold on the forearm at postoperative 24\u00a0h was significantly lower in Group R than in Groups N, D and DN [62.2 (10.7) vs. 71.1 (12.3), 72.4 (12.9) and 78.0 (13.8)\u00a0g]. Compared with Group R, Postoperative pain intensity, analgesic consumption and hyperalgesic area were lower likewise in Groups D and DN. However, the incidence of intraoperative bradycardia was lower and post-anesthesia recovery time was shorter in Group DN than Group D. Preoperative therapy of dexmedetomidine and nalmefene combined attenuates postoperative hyperalgesia in patients undergoing laparoscopic gynecological surgery under desflurane-remifentanil anesthesia.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2023.1131812","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T01:12:21Z","timestamp":1674609141000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Nalmefene vs. dexmedetomidine for prevention of postoperative hyperalgesia in patients undergoing laparoscopic gynecological surgery with remifentanil infusion: A randomized double-blind controlled trial"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhen","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yegong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guolin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1097\/ALN.0b013e3182887526","article-title":"Effects of naloxone on opioid-induced hyperalgesia and tolerance to remifentanil under sevoflurane anesthesia in rats","volume":"118","author":"Aguado","year":"2013","journal-title":"Anesthesiology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"12502","DOI":"10.1523\/JNEUROSCI.1673-15.2015","article-title":"Repeated mu-opioid exposure induces a novel form of the hyperalgesic priming model for transition to chronic pain","volume":"35","author":"Araldi","year":"2015","journal-title":"J. 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