{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:01:51Z","timestamp":1793235711084,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia I.P.","doi-asserted-by":"publisher","award":["2023.00543.BD"],"award-info":[{"award-number":["2023.00543.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Current research reported that the number of clinical studies found for botulinum toxin (BoNT) key effects on biochemical biomarkers in head and neck chronic conditions linked to inflammation was very low. There are no systematic reviews of animal studies on this topic, and hence our review aimed to evaluate the quality of the preclinical evidence. We searched PubMed, Scopus, and Web of Science databases, and registries up to 29 January 2024. There were 22 eligible records, and data were available for 11 randomised controlled trials. There were concerns about the risk of bias and great variations of data obtained regarding chronic conditions, which included mostly trigeminal neuralgia. The leading biomarkers were proinflammatory cytokines (IL-1\u03b2, TNF-\u03b1) and synaptosomal-associated protein-25 (SNAP25), followed by neuron activation marker c-Fos and calcitonin gene-related peptide (CGRP). Overall, data found that BoNT significantly altered the under\/over-expression of biomarkers evoked by the investigated disease models and had no effect when the levels of these biomarkers were not changed by the induced chronic conditions in animals. However, there were some mixed results and exceptions, and the certainty evidence found was very low to low. Although the sample sizes detected significant effect size (p &lt; 0.05), most studies are based on male inferior animals, which may limit the recommendations for clinical trials. This study is registered on PROSPERO (CRD42023432411).<\/jats:p>","DOI":"10.3390\/toxins17080377","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T12:39:29Z","timestamp":1753792769000},"page":"377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Botulinum Toxin Effects on Biochemical Biomarkers Related to Inflammation-Associated Head and Neck Chronic Conditions: A Systematic Review of Preclinical Research"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8806-3863","authenticated-orcid":false,"given":"Ines","family":"Novo Pereira","sequence":"first","affiliation":[{"name":"Faculty of Dental Medicine, University of Porto (FMDUP), Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"},{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health & Science, 2829-511 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0921-342X","authenticated-orcid":false,"given":"Giancarlo","family":"De la Torre Canales","sequence":"additional","affiliation":[{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health & Science, 2829-511 Almada, Portugal"},{"name":"Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, SE-14104 Huddinge, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5881-4021","authenticated-orcid":false,"given":"Sara","family":"Dur\u00e3o","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, University of Porto (FMDUP), Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8157-2292","authenticated-orcid":false,"given":"Rawand","family":"Shado","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, Royal London Dental Hospital, Faculty of Medicine & Dentistry, Queen Mary University, Turner Street, London E1 2AD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1991-9418","authenticated-orcid":false,"given":"Ana Cristina","family":"Braga","sequence":"additional","affiliation":[{"name":"School of Engineering (EEUM) ALGORITMI Research Centre, The Intelligent Systems Associate Laboratory (LASI), Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-2825","authenticated-orcid":false,"given":"Andr\u00e9 Mariz","family":"Almeida","sequence":"additional","affiliation":[{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health & Science, 2829-511 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8192-9916","authenticated-orcid":false,"given":"Haidar","family":"Hassan","sequence":"additional","affiliation":[{"name":"Centre for Cutaneous Research, Blizard Institute of Cell and Molecular Science, Faculty of Medicine & Dentistry, Queen Mary University of London (QMUL), 4 Newark Street, Whitechapel, London E1 2AT, UK"},{"name":"Department of Dental Implantology, Rey Juan Carlos University (URJC), Av. de Atenas, S\/N, 28922 Alcorc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9881-3338","authenticated-orcid":false,"given":"Ana Cristina","family":"Manso","sequence":"additional","affiliation":[{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health & Science, 2829-511 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9265-0913","authenticated-orcid":false,"given":"Ricardo","family":"Faria-Almeida","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Periodontology and Oral Surgery Department, Faculty of Dental Medicine, University of Porto (FMDUP), Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3844\/crdsp.2021.62.70","article-title":"The Anti-Nociceptive\/Anti-Inflammatory Actions of Botulinum Toxin A for the Treatment of Chronic Pain: A Literature Review","volume":"12","author":"Hajj","year":"2021","journal-title":"Curr. 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