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We show that alternative splicing of\n                  <jats:italic>Cadps<\/jats:italic>\n                  , encoding the vesicle-priming factor CAPS1, generates nociceptor-selective Ca\n                  <jats:sub>V<\/jats:sub>\n                  2.2 regulation and underlies inflammatory pain hypersensitivity. Although\n                  <jats:italic>Cadps<\/jats:italic>\n                  is comparably expressed across dorsal root ganglion neurons, exon-resolution analysis identified exon 16a, a conserved 23-amino-acid cassette, as selectively enriched in nociceptors. The e16a-containing CAPS1 isoform, but not CAPS1 lacking e16a, enhanced recombinant Ca\n                  <jats:sub>V<\/jats:sub>\n                  2.2 currents, whereas disruption of the e16a-encoded sequence blocked this effect and reduced endogenous Ca\n                  <jats:sub>V<\/jats:sub>\n                  2.2 currents in nociceptors. Conditional\n                  <jats:italic>Cadps<\/jats:italic>\n                  deletion in Trpv1-lineage nociceptors similarly reduced Ca\n                  <jats:sub>V<\/jats:sub>\n                  2.2 currents and attenuated capsaicin-evoked inflammatory hypersensitivity while sparing baseline sensitivity, an effect replicated by intrathecal delivery of an exon 16a-derived peptide. Alternative splicing of a presynaptic partner protein thus confers cell-type-specific Ca\n                  <jats:sub>V<\/jats:sub>\n                  2.2 coupling and underlies inflammatory pain hypersensitivity.\n                <\/jats:p>","DOI":"10.64898\/2026.05.23.727326","type":"posted-content","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:15:29Z","timestamp":1779920129000},"source":"Crossref","is-referenced-by-count":0,"title":["Nociceptor-enriched CAPS1 isoform couples to Ca\n                  <sub>V<\/sub>\n                  2.2 channels and underlies inflammatory pain hypersensitivity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1302-4001","authenticated-orcid":false,"given":"Melissa","family":"Daeschner","sequence":"first","affiliation":[{"name":"Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio Rom\u00e1n","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andi","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quiana Tyss","family":"Mosley","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3298-8001","authenticated-orcid":false,"given":"Eduardo Javier","family":"L\u00f3pez Soto","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052921001848000_2026.05.23.727326v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.09.005"},{"key":"2026052921001848000_2026.05.23.727326v1.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021113-170338"},{"key":"2026052921001848000_2026.05.23.727326v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.028"},{"key":"2026052921001848000_2026.05.23.727326v1.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0195-21.2021"},{"key":"2026052921001848000_2026.05.23.727326v1.5","doi-asserted-by":"crossref","unstructured":"L. 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