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This review evaluates whether current experimental models accurately reflect CIPN, emphasizing recent molecular and cellular findings, especially the role of sensory ion channels. We outline limitations of existing models and propose more translational preclinical approaches to better capture disease complexity and patient variability. Improved models could enhance understanding of chemotherapy effects on peripheral nerves and support the development of interventions to prevent or mitigate CIPN. Prioritizing supportive care that minimizes treatment side effects may ultimately improve outcomes and patient wellbeing.<\/jats:p>","DOI":"10.3389\/fphar.2026.1762734","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T07:30:49Z","timestamp":1782199849000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Decoding chemotherapy-induced peripheral neuropathy: ion channels, disease models, and future directions"],"prefix":"10.3389","volume":"17","author":[{"given":"Angela","family":"Lamberti","sequence":"first","affiliation":[{"name":"IDiBE - Instituto de Investigaci\u00f3n, Desarrollo en Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche, Universidad Miguel Hern\u00e1ndez, Elche","place":["Alicante, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Villalba-Riquelme","sequence":"additional","affiliation":[{"name":"Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division of Medicine, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asia","family":"Fern\u00e1ndez-Carvajal","sequence":"additional","affiliation":[{"name":"IDiBE - Instituto de Investigaci\u00f3n, Desarrollo en Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche, Universidad Miguel Hern\u00e1ndez, Elche","place":["Alicante, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ferrer-Montiel","sequence":"additional","affiliation":[{"name":"IDiBE - Instituto de Investigaci\u00f3n, Desarrollo en Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche, Universidad Miguel Hern\u00e1ndez, Elche","place":["Alicante, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.3390\/ijms22041975","article-title":"The role of nucleotide excision repair in cisplatin-induced peripheral neuropathy: mechanism, prevention, and treatment","volume":"22","author":"Acklin","year":"2021","journal-title":"Int. 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