{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:17:01Z","timestamp":1778253421992,"version":"3.51.4"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The epidermal growth factor receptor (EGFR; ErbB1), a membrane bound receptor tyrosine kinase, is hypothesized to have an inhibitory influence on peripheral nerve regeneration. This study examines the impact of EGFR inhibition on nerve regeneration using the commercially available small molecule inhibitor gefitinib.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>In vitro assays included neurite outgrowth of cultured dorsal root ganglion (DRG) neurons from adult C57Bl\/6 wildtype mice on immobilized chondroitin sulfate proteoglycans (CSPG). Following forelimb median nerve injury, EGFR expression, number of regenerated neurons (using retrograde labeling) and myelination of motor and sensory neurons were compared between mice that received either gefitinib or vehicle. Functional recovery was assessed using grip strength.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EGFR expression on DRG and spinal motor neurons was confirmed. Gefitinib significantly increased neurite outgrowth in medium sized (30\u201350\u2009\u03bcm) DRG neurons, resulting in longer neurites (183\u2009\u00b1\u200936\u2009\u03bcm) compared with CSPG alone (49\u2009\u00b1\u20099\u2009\u03bcm). After median nerve injury, significantly greater numbers of sensory neurons (638\u2009\u00b1\u2009112 vs. 301\u2009\u00b1\u200981), but not motor neurons (31\u2009\u00b1\u200912 vs. 42\u2009\u00b1\u200913) regenerated in animals treated with gefitinib compared with controls. Regenerated axons in gefitinib treated animals displayed significantly greater diameter and increased g\u2010ratio compared with controls. Grip strength recovered more quickly in animals receiving gefitinib compared with controls (27.6 vs. 19.1\u2009g 18\u2009days post\u2010injury).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study provides data supporting the role of EGFR as a negative regulator of sensory but not motor neuron regeneration. Further, it demonstrates versatile potential uses of existing pharmaceuticals.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28291","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T07:31:37Z","timestamp":1731396697000},"page":"113-123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The epidermal growth factor receptor inhibitor gefitinib enhances in vitro and in vivo sensory axon regeneration and functional recovery following transection in a mouse median nerve injury model"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1050-4360","authenticated-orcid":false,"given":"Maxwell","family":"Topley","sequence":"first","affiliation":[{"name":"Department of Surgery Queen's University  Kingston Ontario Canada"},{"name":"Centre for Neuroscience Studies Queen's University  Kingston Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1230-0997","authenticated-orcid":false,"given":"Payton","family":"Sparks","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies Queen's University  Kingston Ontario Canada"},{"name":"Marian University College of Osteopathic Medicine  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Marie","family":"Crotty","sequence":"additional","affiliation":[{"name":"Department of Surgery Queen's University  Kingston Ontario Canada"},{"name":"Centre for Neuroscience Studies Queen's University  Kingston Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Kawaja","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies Queen's University  Kingston Ontario Canada"},{"name":"Department of Biomedical and Molecular Sciences Queen's University  Kingston Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0108-9120","authenticated-orcid":false,"given":"J. 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