{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:03:30Z","timestamp":1787065410636,"version":"build-2736575974"},"reference-count":241,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1072113"],"award-info":[{"award-number":["APP1072113"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Voltage-gated sodium channels (NaVs) are a key determinant of neuronal signalling. Neurotoxins from diverse taxa that selectively activate or inhibit NaV channels have helped unravel the role of NaV channels in diseases, including chronic pain. Spider venoms contain the most diverse array of inhibitor cystine knot (ICK) toxins (knottins). This review provides an overview on how spider knottins modulate NaV channels and describes the structural features and molecular determinants that influence their affinity and subtype selectivity. Genetic and functional evidence support a major involvement of NaV subtypes in various chronic pain conditions. The exquisite inhibitory properties of spider knottins over key NaV subtypes make them the best lead molecules for the development of novel analgesics to treat chronic pain.<\/jats:p>","DOI":"10.3390\/toxins11110626","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T05:18:26Z","timestamp":1572499106000},"page":"626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3114-1167","authenticated-orcid":false,"given":"Yashad","family":"Dongol","sequence":"first","affiliation":[{"name":"Division of Chemistry and Structural Biology\/Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0068-9974","authenticated-orcid":false,"given":"Fernanda","family":"C. Cardoso","sequence":"additional","affiliation":[{"name":"Division of Chemistry and Structural Biology\/Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3470-923X","authenticated-orcid":false,"given":"Richard","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Chemistry and Structural Biology\/Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,29]]},"reference":[{"key":"ref_1","unstructured":"Kastin, A.J. (2013). Spider Peptides. Handbook of Biologically Active Peptides, Academic Press. [2nd ed.]."},{"key":"ref_2","unstructured":"Catalog, W.S. (2019, June 25). World Spider Catalog. 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