{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:10:25Z","timestamp":1781154625632,"version":"3.54.1"},"reference-count":39,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2017,12,4]],"date-time":"2017-12-04T00:00:00Z","timestamp":1512345600000},"content-version":"vor","delay-in-days":1068,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"crossref","award":["2010_A31"],"award-info":[{"award-number":["2010_A31"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bjanaesthesia.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["British Journal of Anaesthesia"],"published-print":{"date-parts":[[2015,1]]},"DOI":"10.1093\/bja\/aeu206","type":"journal-article","created":{"date-parts":[[2014,7,10]],"date-time":"2014-07-10T20:20:57Z","timestamp":1405023657000},"page":"110-120","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":25,"title":["Methadone is a local anaesthetic-like inhibitor of neuronal Na+ channels and blocks excitability of mouse peripheral nerves"],"prefix":"10.1016","volume":"114","author":[{"given":"C.","family":"Stoetzer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Kistner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"St\u00fcber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Wirths","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Doll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Foadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Wegner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Ahrens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Leffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1093\/bja\/aeu206_bib1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fphar.2011.00068","article-title":"The sodium channel as a target for local anaesthetic drugs","volume":"2","author":"Fozzard","year":"2011","journal-title":"Front Pharmacol"},{"key":"10.1093\/bja\/aeu206_bib2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1097\/ACO.0b013e32832ee847","article-title":"Local anaesthetic adjuvants: neuraxial versus peripheral nerve block","volume":"22","author":"Axelsson","year":"2009","journal-title":"Curr Opin Anaesthesiol"},{"key":"10.1093\/bja\/aeu206_bib3","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.pain.2011.11.028","article-title":"Opioids added to local anaesthetics for single-shot intrathecal anaesthesia in patients undergoing minor surgery: a meta-analysis of randomized trials","volume":"153","author":"Popping","year":"2012","journal-title":"Pain"},{"key":"10.1093\/bja\/aeu206_bib4","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/j.pain.2013.04.023","article-title":"Combination of a reduced dose of an intrathecal local anaesthetic with a small dose of an opioid: a meta-analysis of randomized trials","volume":"154","author":"Popping","year":"2013","journal-title":"Pain"},{"key":"10.1093\/bja\/aeu206_bib5","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/ALN.0b013e3182557917","article-title":"Local anaesthetic-like inhibition of voltage-gated Na(+) channels by the partial mu-opioid receptor agonist buprenorphine","volume":"116","author":"Leffler","year":"2012","journal-title":"Anesthesiology"},{"key":"10.1093\/bja\/aeu206_bib6","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.pain.2006.07.003","article-title":"Tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium channels","volume":"126","author":"Haeseler","year":"2006","journal-title":"Pain"},{"key":"10.1093\/bja\/aeu206_bib7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.5055\/jom.2012.0114","article-title":"A review of epidural and intrathecal opioids used in the management of postoperative pain","volume":"8","author":"Bujedo","year":"2012","journal-title":"J Opioid Manag"},{"key":"10.1093\/bja\/aeu206_bib8","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/bja\/aet234","article-title":"Enhanced antinociceptive efficacy of epidural compared with i.v. methadone in a rat model of thermal nociception","volume":"1","author":"Haroutiunian","year":"2014","journal-title":"Br J Anaesth"},{"key":"10.1093\/bja\/aeu206_bib9","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ejphar.2010.04.020","article-title":"Topical methadone and meperidine analgesic synergy in the mouse","volume":"638","author":"Kolesnikov","year":"2010","journal-title":"Eur J Pharmacol"},{"key":"10.1093\/bja\/aeu206_bib10","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/FJC.0b013e3181f1d21b","article-title":"Increased cardiac risk in concomitant methadone and diazepam treatment: pharmacodynamic interactions in cardiac ion channels","volume":"56","author":"Kuryshev","year":"2010","journal-title":"J Cardiovasc Pharmacol"},{"key":"10.1093\/bja\/aeu206_bib11","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/bph.12465","article-title":"The opioid methadone induces a local anaesthetic like inhibition of the cardiac Na+ channel Nav1.5","volume":"171","author":"Schulze","year":"2014","journal-title":"Br J Pharmacol"},{"key":"10.1093\/bja\/aeu206_bib12","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/sj.clpt.6100120","article-title":"Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers","volume":"81","author":"Eap","year":"2007","journal-title":"Clin Pharmacol Ther"},{"key":"10.1093\/bja\/aeu206_bib13","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1213\/01.ANE.0000099723.75548.DF","article-title":"Functional inhibition by methadone of N-methyl-d-aspartate receptors expressed in Xenopus oocytes: stereospecific and subunit effects","volume":"98","author":"Callahan","year":"2004","journal-title":"Anesth Analg"},{"key":"10.1093\/bja\/aeu206_bib14","doi-asserted-by":"crossref","first-page":"PL45","DOI":"10.1016\/0024-3205(94)00937-6","article-title":"The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine","volume":"56","author":"Kristensen","year":"1995","journal-title":"Life Sci"},{"key":"10.1093\/bja\/aeu206_bib15","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1124\/mol.108.053322","article-title":"Direct subunit-dependent multimodal 5-hydroxytryptamine3 receptor antagonism by methadone","volume":"75","author":"Deeb","year":"2009","journal-title":"Mol Pharmacol"},{"key":"10.1093\/bja\/aeu206_bib16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00232-004-0702-y","article-title":"Interactions of local anaesthetics with voltage-gated Na+ channels","volume":"201","author":"Nau","year":"2004","journal-title":"J Membr Biol"},{"key":"10.1093\/bja\/aeu206_bib17","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1124\/jpet.106.109025","article-title":"Use-dependent block by lidocaine but not amitriptyline is more pronounced in tetrodotoxin (TTX)-Resistant Nav1.8 than in TTX-sensitive Na+ channels","volume":"320","author":"Leffler","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1093\/bja\/aeu206_bib18","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1523\/JNEUROSCI.2804-12.2013","article-title":"Phenotyping the function of TRPV1-expressing sensory neurons by targeted axonal silencing","volume":"33","author":"Brenneis","year":"2013","journal-title":"J Neurosci"},{"key":"10.1093\/bja\/aeu206_bib19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ejphar.2009.12.027","article-title":"Block of sensory neuronal Na+ channels by the secreolytic ambroxol is associated with an interaction with local anaesthetic binding sites","volume":"630","author":"Leffler","year":"2010","journal-title":"Eur J Pharmacol"},{"key":"10.1093\/bja\/aeu206_bib20","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/cne.21786","article-title":"Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons","volume":"510","author":"Fukuoka","year":"2008","journal-title":"J Comp Neurol"},{"key":"10.1093\/bja\/aeu206_bib21","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00424-009-0779-3","article-title":"Sodium channelopathies and pain","volume":"460","author":"Lampert","year":"2010","journal-title":"Pflugers Arch"},{"key":"10.1093\/bja\/aeu206_bib22","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/1744-8069-7-67","article-title":"Identification of sodium channel isoforms that mediate action potential firing in lamina I\/II spinal cord neurons","volume":"7","author":"Hildebrand","year":"2011","journal-title":"Mol Pain"},{"key":"10.1093\/bja\/aeu206_bib23","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1097\/ALN.0b013e318221fcc9","article-title":"Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the duration of analgesia by blocking the hyperpolarization-activated cation current","volume":"115","author":"Brummett","year":"2011","journal-title":"Anesthesiology"},{"key":"10.1093\/bja\/aeu206_bib24","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1097\/ALN.0b013e3181bbcc26","article-title":"Perineural dexmedetomidine added to ropivacaine causes a dose-dependent increase in the duration of thermal antinociception in sciatic nerve block in rat","volume":"111","author":"Brummett","year":"2009","journal-title":"Anesthesiology"},{"key":"10.1093\/bja\/aeu206_bib25","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1124\/mol.110.070227","article-title":"Local anaesthetic inhibits hyperpolarization-activated cationic currents","volume":"79","author":"Meng","year":"2011","journal-title":"Mol Pharmacol"},{"key":"10.1093\/bja\/aeu206_bib26","doi-asserted-by":"crossref","first-page":"3713","DOI":"10.1152\/jn.00841.2006","article-title":"Direct inhibition of Ih by analgesic loperamide in rat DRG neurons","volume":"97","author":"Vasilyev","year":"2007","journal-title":"J Neurophysiol"},{"key":"10.1093\/bja\/aeu206_bib27","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1126\/science.1206243","article-title":"HCN2 ion channels play a central role in inflammatory and neuropathic pain","volume":"333","author":"Emery","year":"2011","journal-title":"Science"},{"key":"10.1093\/bja\/aeu206_bib28","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S1521-6896(02)00113-1","article-title":"Neurotoxicity of intrathecal local anaesthetics and transient neurological symptoms","volume":"17","author":"Pollock","year":"2003","journal-title":"Best Pract Res Clin Anaesthesiol"},{"key":"10.1093\/bja\/aeu206_bib29","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1097\/00000542-199911000-00042","article-title":"Meperidine and lidocaine block of recombinant voltage-dependent Na+ channels: evidence that meperidine is a local anaesthetic","volume":"91","author":"Wagner","year":"1999","journal-title":"Anesthesiology"},{"key":"10.1093\/bja\/aeu206_bib30","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S0304-3959(03)00205-7","article-title":"QTc interval prolongation associated with intravenous methadone","volume":"105","author":"Kornick","year":"2003","journal-title":"Pain"},{"key":"10.1093\/bja\/aeu206_bib31","first-page":"182","article-title":"Postoperative analgesia with epidural methadone in patients operated for hernia of the lumbar disc","volume":"44","author":"Hernandez-Palazon","year":"1997","journal-title":"Rev Esp Anestesiol Reanim"},{"key":"10.1093\/bja\/aeu206_bib32","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/S0022-3565(25)03418-4","article-title":"Pharmacologic comparison of the optical isomers of methadon","volume":"93","author":"Scott","year":"1948","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1093\/bja\/aeu206_bib33","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.pain.2005.06.030","article-title":"Different profiles of buprenorphine-induced analgesia and antihyperalgesia in a human pain model","volume":"118","author":"Koppert","year":"2005","journal-title":"Pain"},{"key":"10.1093\/bja\/aeu206_bib34","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3109\/15360288.2011.589490","article-title":"Pharmacological treatment of opioid-induced hyperalgesia: a review of the evidence","volume":"25","author":"Ramasubbu","year":"2011","journal-title":"J Pain Palliat Care Pharmacother"},{"key":"10.1093\/bja\/aeu206_bib35","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1213\/ane.0b013e31819385e1","article-title":"Cytotoxicity of local anaesthetics in human neuronal cells","volume":"108","author":"Perez-Castro","year":"2009","journal-title":"Anesth Analg"},{"key":"10.1093\/bja\/aeu206_bib36","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1097\/AAP.0b013e318226ba62","article-title":"The influence of adjuvants used in regional anaesthesia on lidocaine-induced neurotoxicity in vitro","volume":"36","author":"Werdehausen","year":"2011","journal-title":"Reg Anesth Pain Med"},{"key":"10.1093\/bja\/aeu206_bib37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/AAP.0b013e3182176f70","article-title":"Neurotoxicity of adjuvants used in perineural anaesthesia and analgesia in comparison with ropivacaine","volume":"36","author":"Williams","year":"2011","journal-title":"Reg Anesth Pain Med"},{"key":"10.1093\/bja\/aeu206_bib38","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1097\/ALN.0b013e31816c902a","article-title":"Toxicology profile of N-methyl-d-aspartate antagonists delivered by intrathecal infusion in the canine model","volume":"108","author":"Yaksh","year":"2008","journal-title":"Anesthesiology"},{"key":"10.1093\/bja\/aeu206_bib39","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1093\/bja\/aep236","article-title":"Apoptosis induction by different local anaesthetics in a neuroblastoma cell line","volume":"103","author":"Werdehausen","year":"2009","journal-title":"Br J Anaesth"}],"container-title":["British Journal of Anaesthesia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0007091217305767?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0007091217305767?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/academic.oup.com\/bja\/article-pdf\/114\/1\/110\/9590311\/aeu206.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T18:30:26Z","timestamp":1757788226000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0007091217305767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["S0007091217305767"],"URL":"https:\/\/doi.org\/10.1093\/bja\/aeu206","relation":{},"ISSN":["0007-0912"],"issn-type":[{"value":"0007-0912","type":"print"}],"subject":[],"published":{"date-parts":[[2015,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Methadone is a local anaesthetic-like inhibitor of neuronal Na+ channels and blocks excitability of mouse peripheral nerves","name":"articletitle","label":"Article Title"},{"value":"British Journal of Anaesthesia","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1093\/bja\/aeu206","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2015 The Author(s). Published by Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}