{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:04:40Z","timestamp":1780491880245,"version":"3.54.1"},"reference-count":84,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["15\/IA\/3026"],"award-info":[{"award-number":["15\/IA\/3026"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Chimeras of botulinum neurotoxin (BoNT) serotype A (\/A) combined with \/E protease might possess improved analgesic properties relative to either parent, due to inheriting the sensory neurotropism of the former with more extensive disabling of SNAP-25 from the latter. Hence, fusions of \/E protease light chain (LC) to whole BoNT\/A (LC\/E-BoNT\/A), and of the LC plus translocation domain (HN) of \/E with the neuronal acceptor binding moiety (HC) of \/A (BoNT\/EA), created previously by gene recombination and expression in E. coli., were used. LC\/E-BoNT\/A (75 units\/kg) injected into the whisker pad of rats seemed devoid of systemic toxicity, as reflected by an absence of weight loss, but inhibited the nocifensive behavior (grooming, freezing, and reduced mobility) induced by activating TRPV1 with capsaicin, injected at various days thereafter. No sex-related differences were observed. c-Fos expression was increased five-fold in the trigeminal nucleus caudalis ipsi-lateral to capsaicin injection, relative to the contra-lateral side and vehicle-treated controls, and this increase was virtually prevented by LC\/E-BoNT\/A. In vitro, LC\/E-BoNT\/A or \/EA diminished CGRP exocytosis from rat neonate trigeminal ganglionic neurons stimulated with up to 1 \u00b5M capsaicin, whereas BoNT\/A only substantially reduced the release in response to 0.1 \u00b5M or less of the stimulant, in accordance with the \/E protease being known to prevent fusion of exocytotic vesicles.<\/jats:p>","DOI":"10.3390\/toxins14020116","type":"journal-article","created":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T20:40:18Z","timestamp":1644180018000},"page":"116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Botulinum Neurotoxin Chimeras Suppress Stimulation by Capsaicin of Rat Trigeminal Sensory Neurons In Vivo and In Vitro"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4285-8956","authenticated-orcid":false,"given":"Caren","family":"Antoniazzi","sequence":"first","affiliation":[{"name":"International Centre for Neurotherapeutics, Dublin City University, Collins Avenue, D09 V209 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1326-4948","authenticated-orcid":false,"given":"Mariia","family":"Belinskaia","sequence":"additional","affiliation":[{"name":"International Centre for Neurotherapeutics, Dublin City University, Collins Avenue, D09 V209 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Zurawski","sequence":"additional","affiliation":[{"name":"International Centre for Neurotherapeutics, Dublin City University, Collins Avenue, D09 V209 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seshu Kumar","family":"Kaza","sequence":"additional","affiliation":[{"name":"International Centre for Neurotherapeutics, Dublin City University, Collins Avenue, D09 V209 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Oliver","family":"Dolly","sequence":"additional","affiliation":[{"name":"International Centre for Neurotherapeutics, Dublin City University, Collins Avenue, D09 V209 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary W.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"International Centre for Neurotherapeutics, Dublin City University, Collins Avenue, D09 V209 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"ref_1","unstructured":"Atassi, M.Z. (2009). Multiple Steps in the Blockade of Exocytosis by Botulinum Neurotoxins. Botulinum Toxin: Therapeutic Clinical Practice and Science, Saunders Elsevier. 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