{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T02:59:01Z","timestamp":1793761141610,"version":"4.6.1"},"reference-count":67,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    OnabotulinumtoxinA (onabotA), a Botulinum neurotoxin type A (BoNT\/A), is an effective treatment for chronic migraine, but its direct mechanism of action on human sensory neurons has not been fully elucidated. While rodent studies on dorsal root ganglion (DRG) and trigeminal ganglion (TG) show that BoNT\/A inhibits neurotransmission, including calcitonin gene\u2010related peptide (CGRP\/\n                    <jats:italic>CALCA<\/jats:italic>\n                    ) release, by cleaving synaptosomal\u2010associated protein 25 (SNAP\u201025), only one previous study has assessed its effect on human DRG neurons. The objective of this study was to understand the mechanism of action of BoNT\/A in cultured human sensory neurons and assess, using RNA sequencing, the transcriptomic consequences of BoNT\/A treatment. Using DRGs obtained from organ donors, the expression of key targets, including synaptic vesicle glycoprotein 2C (\n                    <jats:italic>SV2C<\/jats:italic>\n                    ),\n                    <jats:italic>SNAP25<\/jats:italic>\n                    , &amp;\n                    <jats:italic>CALCA<\/jats:italic>\n                    , was validated by mining existing transcriptomic datasets as well as immunohistochemistry. Cultured dissociated human DRG neurons treated with BoNT\/A were used to examine cleavage of SNAP25, release of CGRP, and transcriptomic changes after BoNT\/A treatment. SV2C was found to be widely expressed in human DRG neurons in a pattern that completely overlapped with CGRP expression. Consistent with this finding, BoNT\/A disrupted soluble N\u2010ethylmaleimide\u2010sensitive factor attachment protein receptor (SNARE) protein complexes in human DRG neurons as demonstrated by SNAP\u201025 cleavage in most somatosensory neurons and a reduction in capsaicin\u2010evoked CGRP release, indicating impaired vesicle fusion. Moreover, bulk RNA sequencing experiments revealed downregulated expression of a large subset of genes responsible for neurotransmitter and neuropeptide release from neurons, suggesting a novel mechanism through which BoNT\/A regulates neurotransmission. These results provide new insight into the molecular mechanisms by which BoNT\/A may exert its pain\u2010relieving effects in humans.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70236-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70236","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T12:11:26Z","timestamp":1758024686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Botulinum Neurotoxin A Signaling in Pain Modulation Within Human Sensory Neurons"],"prefix":"10.1111","volume":"169","author":[{"given":"Katherin A.","family":"Gabriel","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Center for Advanced Pain Studies University of Texas at Dallas  Richardson Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kali","family":"Hankerd","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Center for Advanced Pain Studies University of Texas at Dallas  Richardson Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulino","family":"Barragan\u2010Iglesias","sequence":"additional","affiliation":[{"name":"Allergan Aesthetics An AbbVie Company  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy D.","family":"Brideau\u2010Andersen","sequence":"additional","affiliation":[{"name":"Allergan Aesthetics An AbbVie Company  Irvine California 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