{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:53:12Z","timestamp":1791546792584,"version":"4.3.4"},"reference-count":111,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technology &amp; Innovation, Science Fund Scheme","award":["Grant 5450778"],"award-info":[{"award-number":["Grant 5450778"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Zerumbone, a monocyclic sesquiterpene from the wild ginger plant Zingiber zerumbet (L.) Smith, attenuates allodynia and hyperalgesia. Currently, its mechanisms of action in neuropathic pain conditions remain unclear. This study examines the involvement of potassium channels and opioid receptors in zerumbone-induced analgesia in a chronic constriction injury (CCI) neuropathic pain mice model. Male Institute of Cancer Research (ICR) mice were subjected to CCI and behavioral responses were tested on day 14. Responses toward mechanical allodynia and thermal hyperalgesia were tested with von Frey\u2019s filament and Hargreaves\u2019 tests, respectively. Symptoms of neuropathic pain were significantly alleviated following treatment with zerumbone (10 mg\/kg; intraperitoneal, i.p.). However, when the voltage-dependent K+ channel blocker tetraethylammonium (TEA, 4 mg\/kg; i.p.), ATP-sensitive K+ channel blocker, glibenclamide (GLIB, 10 mg\/kg; i.p.); small-conductance Ca2+-activated K+ channel inhibitor apamin (APA, 0.04 mg\/kg; i.p.), or large-conductance Ca2+-activated K+ channel inhibitor charybdotoxin (CHAR, 0.02 mg\/kg; i.p.) was administered prior to zerumbone (10 mg\/kg; i.p.), the antiallodynic and antihyperalgesic effects of zerumbone were significantly reversed. Additionally, non-specific opioid receptors antagonist, naloxone (NAL, 10 mg\/kg; i.p.), selective \u00b5-, \u03b4- and \u03ba-opioid receptor antagonists; \u03b2-funaltrexamine (\u03b2-FN, 40 mg\/kg; i.p.), naltrindole (20 mg\/kg; s.c.), nor-binaltorphamine (10 mg\/kg; s.c.) respectively attenuated the antiallodynic and antihyperalgesic effects of zerumbone. This outcome clearly demonstrates the participation of potassium channels and opioid receptors in the antineuropathic properties of zerumbone. As various clinically used neuropathic pain drugs also share this similar mechanism, this compound is, therefore, a highly potential substitute to these therapeutic options.<\/jats:p>","DOI":"10.3390\/molecules25173880","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T09:56:58Z","timestamp":1598435818000},"page":"3880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Zerumbone-Induced Analgesia Modulated via Potassium Channels and Opioid Receptors in Chronic Constriction Injury-Induced Neuropathic Pain"],"prefix":"10.3390","volume":"25","author":[{"given":"Banulata","family":"Gopalsamy","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8813-7463","authenticated-orcid":false,"given":"Jasmine Siew Min","family":"Chia","sequence":"additional","affiliation":[{"name":"Centre for Community Health Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Akira Omar","family":"Farouk","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Roslan","family":"Sulaiman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2666-7340","authenticated-orcid":false,"given":"Enoch Kumar","family":"Perimal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"},{"name":"Australian Research Council Centre of Excellence for Nanoscale BioPhotonics, University of Adelaide, Adelaide 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/(SICI)1096-9861(19961209)376:2<241::AID-CNE6>3.0.CO;2-3","article-title":"Sympathetic sprouting in the dorsal root ganglia of the injured peripheral nerve in a rat neuropathic pain model","volume":"376","author":"Chung","year":"1996","journal-title":"J. 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