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OIPN manifests as acute cold-induced paresthesia and chronic cumulative sensory neuropathy, with complex, incompletely elucidated pathophysiological mechanisms. This review systematically summarizes the core molecular mechanisms of OIPN, focusing on: (1) sensitization of transient receptor potential vanilloid\/ankyrin channels (TRPV1\/TRPA1), (2) dysregulated expression and function of voltage-gated sodium channels (NaV1.7, NaV1.8), and (3) the critical role of p38 mitogen-activated protein kinase (p38-MAPK) pathway activation in neuronal hyperexcitability and pain signal transduction within dorsal root ganglion (DRG) sensory neurons. Additionally, we delve into dynamic alterations of the DRG immune microenvironment (notably macrophages and T cells) during OIPN initiation\/progression, as well as their crosstalk with neurons. To address the clinical dilemma of limited effective preventive\/therapeutic approaches, this review outlines limitations of current strategies and highlights the advantages of nanotechnology-based drug delivery systems in enhancing neuroprotective agent bioavailability and enabling targeted delivery. Finally, we hypothesize the integration of salidroside (a natural product with anti-inflammatory\/antioxidant properties) with nanotechnology, and propose leveraging cutting-edge tools (spatial transcriptomics, single-cell RNA sequencing) to elucidate its potential mechanistic action in OIPN\u2014providing a theoretical hypothesis and exploratory research directions for precision OIPN prevention and treatment, in the absence of any empirical evidence for salidroside\u2019s efficacy in this specific pathological context.<\/jats:p>","DOI":"10.1186\/s43046-026-00355-w","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T23:03:49Z","timestamp":1778454229000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nanomedicine against oxaliplatin-induced peripheral neuropathy: hypotheses and research perspectives on ion channels and immune microenvironment"],"prefix":"10.1186","volume":"38","author":[{"given":"Yuan","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"355_CR1","doi-asserted-by":"publisher","first-page":"116820","DOI":"10.1016\/j.biopha.2024.116820","volume":"176","author":"PCS Rietveld","year":"2024","unstructured":"Rietveld PCS, Guchelaar NAD, van Eerden RAG, et al. 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