{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:38:11Z","timestamp":1761514691857,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicines"],"abstract":"<jats:p>Background: Fentanyl can induce acute opioid tolerance and postoperative hyperalgesia when administered at a single high dose; thus, this study examined the analgesic efficacy of a combination of fentanyl and Yokukansan (YKS). Methods: Rats were divided into control, formalin-injected (FOR), YKS-treated+FOR (YKS), fentanyl-treated+FOR (FEN), and YKS+FEN+FOR (YKS+FEN) groups. Acute pain was induced via subcutaneous injection of formalin into the paw. The time engaged in pain-related behavior was measured. Results: In the early (0\u201310 min) and intermediate (10\u201320 min) phases, pain-related behavior in the YKS+FEN group was significantly inhibited compared with the FOR group. In the late phase (20\u201360 min), pain-related behavior in the FEN group was the longest and significantly increased compared with the YKS group. We explored the influence on the extracellular signal-regulated kinase (ERK) pathway in the spinal cord, and YKS suppressed the phosphorylated ERK expression, which may be related to the analgesic effect of YKS in the late phase. Conclusions: These findings suggest that YKS could reduce the use of fentanyl and combined use of YKS and fentanyl is considered clinically useful.<\/jats:p>","DOI":"10.3390\/medicines7120075","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T10:42:47Z","timestamp":1608201767000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analgesic Efficacy of a Combination of Fentanyl and a Japanese Herbal Medicine \u201cYokukansan\u201d in Rats with Acute Inflammatory Pain"],"prefix":"10.3390","volume":"7","author":[{"given":"Yuko","family":"Akanuma","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan"},{"name":"Department of Anesthesiology, St. Luke\u2019s International Hospital, Tokyo 104-8560, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mami","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasunori","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideshi","family":"Ikemoto","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan"},{"name":"Department of Palliative Medicine, Showa University Yokohama Northern Hospital, Kanagawa 224-8503, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wakako","family":"Yogi","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan"},{"name":"Pharmaceutical Department, Showa University Hospital, Tokyo 142-8666, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-6506","authenticated-orcid":false,"given":"Takayuki","family":"Okumo","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mana","family":"Tsukada","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7621-2024","authenticated-orcid":false,"given":"Masataka","family":"Sunagawa","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"598","DOI":"10.6002\/ect.2019.0014","article-title":"Preconditioning effect of remifentanil versus fentanyl in prevalence of early graft dysfunction in patients after liver transplant: A randomized clinical trial","volume":"18","author":"Jowkar","year":"2020","journal-title":"Exp. 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