{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:01:17Z","timestamp":1792807277484,"version":"4.5.0"},"reference-count":94,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:00:00Z","timestamp":1626048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002878","name":"Consejer\u00eda de Econom\u00eda, Innovaci\u00f3n, Ciencia y Empleo, Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["grant CTS 109"],"award-info":[{"award-number":["grant CTS 109"]}],"id":[{"id":"10.13039\/501100002878","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biosanitary Research Institute ibs.GRANADA","award":["INTRAIBS-2020-09"],"award-info":[{"award-number":["INTRAIBS-2020-09"]}],"id":[{"id":"https:\/\/ror.org\/026yy9j15","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006393","name":"Universidad de Granada","doi-asserted-by":"publisher","award":["PPJIA2020-06"],"award-info":[{"award-number":["PPJIA2020-06"]}],"id":[{"id":"10.13039\/501100006393","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Tetrodotoxin (TTX) is a potent neurotoxin found mainly in puffer fish and other marine and terrestrial animals. TTX blocks voltage-gated sodium channels (VGSCs) which are typically classified as TTX-sensitive or TTX-resistant channels. VGSCs play a key role in pain signaling and some TTX-sensitive VGSCs are highly expressed by adult primary sensory neurons. During pathological pain conditions, such as neuropathic pain, upregulation of some TTX-sensitive VGSCs, including the massive re-expression of the embryonic VGSC subtype NaV1.3 in adult primary sensory neurons, contribute to painful hypersensitization. In addition, people with loss-of-function mutations in the VGSC subtype NaV1.7 present congenital insensitive to pain. TTX displays a prominent analgesic effect in several models of neuropathic pain in rodents. According to this promising preclinical evidence, TTX is currently under clinical development for chemo-therapy-induced neuropathic pain and cancer-related pain. This review focuses primarily on the preclinical and clinical evidence that support a potential analgesic role for TTX in these pain states. In addition, we also analyze the main toxic effects that this neurotoxin produces when it is administered at therapeutic doses, and the therapeutic potential to alleviate neuropathic pain of other natural toxins that selectively block TTX-sensitive VGSCs.<\/jats:p>","DOI":"10.3390\/toxins13070483","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T21:56:52Z","timestamp":1626127012000},"page":"483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Tetrodotoxin, a Potential Drug for Neuropathic and Cancer Pain Relief?"],"prefix":"10.3390","volume":"13","author":[{"given":"Rafael","family":"Gonz\u00e1lez-Cano","sequence":"first","affiliation":[{"name":"Department of Pharmacology, and Neurosciences Institute (Biomedical Research Center), University of Granada, 18016 Granada, Spain"},{"name":"Biosanitary Research Institute ibs.GRANADA, 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Carmen","family":"Ruiz-Cantero","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, and Neurosciences Institute (Biomedical Research Center), University of Granada, 18016 Granada, Spain"},{"name":"Biosanitary Research Institute ibs.GRANADA, 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Santos-Caballero","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, and Neurosciences Institute (Biomedical Research Center), University of Granada, 18016 Granada, Spain"},{"name":"Biosanitary Research Institute ibs.GRANADA, 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"G\u00f3mez-Navas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, and Neurosciences Institute (Biomedical Research Center), University of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9323-7626","authenticated-orcid":false,"given":"Miguel \u00c1.","family":"Tejada","sequence":"additional","affiliation":[{"name":"INCLIVA Health Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9555-0651","authenticated-orcid":false,"given":"Francisco R.","family":"Nieto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, and Neurosciences Institute (Biomedical Research Center), University of Granada, 18016 Granada, Spain"},{"name":"Biosanitary Research Institute ibs.GRANADA, 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e779","DOI":"10.1097\/PR9.0000000000000779","article-title":"Prevalence of chronic pain in developing countries: Systematic review and meta-analysis","volume":"4","author":"Moreira","year":"2019","journal-title":"Pain Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.pain.2011.06.017","article-title":"A new definition of neuropathic pain","volume":"152","author":"Jensen","year":"2011","journal-title":"Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17002","DOI":"10.1038\/nrdp.2017.2","article-title":"Neuropathic pain","volume":"3","author":"Colloca","year":"2017","journal-title":"Nat. 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