{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:24:21Z","timestamp":1788449061772,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nonsteroidal anti\u2010inflammatory drugs (NSAIDs) provide effective analgesia but may paradoxically delay tissue recovery, pain resolution and contribute to chronic pain. Erdosteine, a thiol\u2010based prodrug with antioxidant and anti\u2010inflammatory properties, is a mucolytic used for treatment of respiratory diseases but has recently been suggested to possess analgesic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined the analgesic efficacy of erdosteine and its metabolite, Met\u20101, in experimental models of inflammatory and neuropathic pain and compared its effects with diclofenac and gabapentin. Male mice received complete Freund's adjuvant (CFA) or chronic constriction injury (CCI) to induce inflammatory or neuropathic pain, respectively. Erdosteine (100 or 300\u2009mg\/kg, per os), its metabolite MET\u20101 (intravenous), diclofenac (per os), gabapentin (per os), or vehicle (per os or intravenous as appropriate) were administered for 7\u2009days following CFA or CCI. In separate experiments, treatments were initiated prior to CFA. Mechanical allodynia was quantified by von Frey testing. Plasma levels of CXCL1, S100A8\/S100A9, IL\u20101Ra, and 8\u2010isoprostane were measured by ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Erdosteine significantly reduced CFA\u2010induced allodynia, with efficacy comparable to diclofenac and gabapentin. Unlike diclofenac, erdosteine did not delay pain recovery in post\u2010CFA or pre\u2010CFA experimental settings and did not elevate plasma CXCL1 or 8\u2010isoprostane levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Erdosteine provides robust analgesia in an experimental model of inflammatory pain without disrupting inflammation\u2010resolution pathways or increasing oxidative stress, supporting its potential as a safe, non\u2010opioid analgesic. These findings support further investigation of erdosteine as a potential, non\u2010opioid analgesic drug that does not produce the adverse events associated with NSAIDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Perspective<\/jats:title>\n                    <jats:p>Erdosteine produced NSAID\u2010comparable analgesia in inflammatory pain without delaying recovery or increasing oxidative and inflammatory markers. Given concerns that NSAIDs may prolong pain resolution, these findings identify erdosteine as a potential non\u2010opioid alternative that relieves inflammatory pain while preserving physiological healing processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Effective and well\u2010tolerated treatments for chronic pain remain limited. Erdosteine is a clinically approved mucolytic with antioxidant and anti\u2010inflammatory properties whose analgesic potential is largely unexplored. We show that oral erdosteine reduces inflammatory pain and allodynia without delaying recovery, unlike the NSAID diclofenac, which increased systemic markers of inflammation and prolonged pain duration. These findings identify erdosteine as a promising candidate for drug repurposing and support further investigation of its potential utility in pain management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70334","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T10:12:53Z","timestamp":1783764773000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Erdosteine Provides Effective Analgesia in Inflammatory Pain Without Impairing Pain Resolution: A Preclinical Comparison With Non\u2010Steroidal Anti\u2010Inflammatory Drugs"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9662-6865","authenticated-orcid":false,"given":"Lucas","family":"Vasconcelos Lima","sequence":"first","affiliation":[{"name":"Alan Edwards Centre for Research on Pain McGill University  Montreal Quebec Canada"},{"name":"Department of Anesthesia, Faculty of Dentistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Karaky","sequence":"additional","affiliation":[{"name":"Alan Edwards Centre for Research on Pain McGill University  Montreal Quebec Canada"},{"name":"Department of Anesthesia, Faculty of Dentistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Faculty of Dentistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Allegri","sequence":"additional","affiliation":[{"name":"Centre L\u00e9manique de Neuromodulation et Th\u00e9rapie de la Douleur, Ensemble Hospitalier de la C\u00f4te  Morges Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Marchesi","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Govoni","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive","family":"Page","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Science King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luda","family":"Diatchenko","sequence":"additional","affiliation":[{"name":"Alan Edwards Centre for Research on Pain McGill University  Montreal Quebec Canada"},{"name":"Department of Anesthesia, Faculty of Dentistry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/s101650300000"},{"key":"e_1_2_11_3_1","article-title":"Chronic Constriction of the Sciatic Nerve and Pain Hypersensitivity Testing in Rats","volume":"61","author":"Austin P. 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