{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:29:46Z","timestamp":1784917786170,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T00:00:00Z","timestamp":1754092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merz Therapeutics GmbH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The use of Botulinum Neurotoxin A (BoNT\/A) to treat peripheral neuropathic pain from nerve injury has garnered interest for its long-lasting effects and safety. This study examined the effects of IncobotulinumtoxinA (Inco\/A), a BoNT\/A variant without accessory proteins, on nerve regeneration in rats using the chronic constriction injury (CCI) model. Inco\/A was administered perineurally at two time points: on days 0 and 21 post CCI. Functional and histological assessments were conducted to evaluate the effect of Inco\/A on nerve regeneration. Sciatic Functional Index (SFI) measurements and Compound Muscle Action Potential (CMAP) recordings were conducted at different time points following CCI. Inco\/A-treated animals exhibited a 65% improved SFI and 22% reduction in CMAP onset latencies compared to the vehicle-treated group, suggesting accelerated functional nerve recovery. Tissue analysis revealed enhanced remyelination in Inco\/A-treated animals and 60% reduction in CGRP and double S100\u03b2 signal expression compared to controls. Strikingly, 30% reduced immune cell influx into the injury site was observed following Inco\/A treatment, suggesting that its anti-inflammatory effect contributes to nerve regeneration. These findings show that two injections of Inco\/A promote functional recovery by enhancing neuroregeneration and modulating inflammatory processes, supporting the hypothesis that Inco\/A has a neuroprotective and restorative role in nerve injury conditions.<\/jats:p>","DOI":"10.3390\/ijms26157482","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T07:45:11Z","timestamp":1754466311000},"page":"7482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Neuroregenerative Effects of IncobotulinumtoxinA (Inco\/A) in a Nerve Lesion Model of the Rat"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8745-5176","authenticated-orcid":false,"given":"Oscar","family":"S\u00e1nchez-Carranza","sequence":"first","affiliation":[{"name":"Nonclinical Sciences & Operations, Merz Therapeutics GmbH, Eckenheimer Landstra\u00dfe 100, D-60318 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Danysz","sequence":"additional","affiliation":[{"name":"Nonclinical Sciences & Operations, Merz Therapeutics GmbH, Eckenheimer Landstra\u00dfe 100, D-60318 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Fink","sequence":"additional","affiliation":[{"name":"Neurotoxin Biotechnology Development, Merz Therapeutics GmbH, Eckenheimer Landstra\u00dfe 100, D-60318 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Ruitenberg","sequence":"additional","affiliation":[{"name":"Nonclinical Sciences & Operations, Merz Therapeutics GmbH, Eckenheimer Landstra\u00dfe 100, D-60318 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Gravius","sequence":"additional","affiliation":[{"name":"Nonclinical Sciences & Operations, Merz Therapeutics GmbH, Eckenheimer Landstra\u00dfe 100, D-60318 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9044-3638","authenticated-orcid":false,"given":"Jens","family":"Nagel","sequence":"additional","affiliation":[{"name":"Nonclinical Sciences & Operations, Merz Therapeutics GmbH, Eckenheimer Landstra\u00dfe 100, D-60318 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S1474-4422(16)00017-X","article-title":"Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): A randomised, double-blind, placebo-controlled trial","volume":"15","author":"Attal","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.pain.2013.11.013","article-title":"Neuropathic pain in the general population: A systematic review of epidemiological studies","volume":"155","author":"Austin","year":"2014","journal-title":"Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/j.pain.0000000000001365","article-title":"The IASP classification of chronic pain for ICD-11: Chronic neuropathic pain","volume":"160","author":"Scholz","year":"2019","journal-title":"Pain"},{"key":"ref_4","first-page":"964","article-title":"Motor nerve sprouting in human orbicularis muscle after botulinum A injection","volume":"31","author":"Holds","year":"1990","journal-title":"Investig. 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