{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T01:06:48Z","timestamp":1790557608323,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"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":["IJMS"],"abstract":"<jats:p>Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia\u2014a locus for craniofacial sensory nerves\u2014were used to examine how NGF affects the Ca2+-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca2+-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT\/A) or a chimera of\/E and\/A (\/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca2+-independent enhancement of the neuropeptide release evoked by low concentrations (&lt;100 nM) of CAP, but only marginally increased the peak response to \u2265100 nM. Notably, BoNT\/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas\/EA effectively reduced responses up to 1 \u00b5M CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181\u2013197 and 198\u2013206) to support CAP-evoked Ca2+-dependent exocytosis at different intensities of stimulation.<\/jats:p>","DOI":"10.3390\/ijms23020892","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T12:34:04Z","timestamp":1642163644000},"page":"892","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1326-4948","authenticated-orcid":false,"given":"Mariia","family":"Belinskaia","sequence":"first","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4285-8956","authenticated-orcid":false,"given":"Caren","family":"Antoniazzi","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":[[2022,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41583-021-00523-y","article-title":"The sympathetic nervous system in development and disease","volume":"22","author":"Boehm","year":"2021","journal-title":"Nat. Rev. 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