ArticleProceedings of the National Academy of Sciences of the United States of America2012
Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype Na(V)1.6-resurgent and persistent current.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 205 citations in OpenAlex.
- Traditional Chinese Medicine syndrome analysis on oxaliplatin-induced peripheral neuropathy and clinical efficacy of Bushen Yiqi formula: a prospective randomized controlled study.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2023Trial
- Characterization of Patients With and Without Painful Peripheral Neuropathy After Receiving Neurotoxic Chemotherapy: Traditional Quantitative Sensory Testing vs C-Fiber and Aδ-Fiber Selective Diode Laser Stimulation.The journal of pain · 2022Trial
- Trial
- Neu-horizons: neuroprotection and therapeutic use of riluzole for the prevention of oxaliplatin-induced neuropathy-a randomised controlled trial.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2021Trial
- Cold aggravates abnormal excitability of motor axons in oxaliplatin-treated patients.Muscle & nerve · 2020Trial
- Sea-anemone toxin ATX-II elicits A-fiber-dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons.Molecular pain · 2012Trial
- Cancer-related pain: A bidirectional modulator of cancer progression.Clinical and translational medicine · 2026Review
- Circular RNA circNrip1 Interacts with SYNCRIP to Promote Neuropathic Pain by Stabilizing Tlr2 mRNA in Primary Sensory Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Association between voltage-gated sodium channel gene polymorphisms and chronic oxaliplatin-induced peripheral neuropathy in Japanese patients with colorectal cancer.Journal of pharmaceutical health care and sciences · 2026Article
- Peripheral Nerve Surgery and Chemotherapy: A Review, Index, and Decision Tree for Nerve Surgeons Considering Neurotization After Oncological Nerve Injuries.Neurosurgery practice · 2026Review
- Contribution of proneurotrophin-3 to nerve trauma-induced neuropathic pain through promoting TrkC-mediated increase of CCL2 in primary sensory neurons.Brain, behavior, and immunity · 2026Article
- The Kv4.3 channel on c-low threshold mechanoreceptors in DRG is a key mediator transforming tactile stimuli into nociceptive signals in chemotherapy-induced neuropathy.Acta pharmaceutica Sinica. B · 2026Article
- Artificial intelligence applications in oxaliplatin-based chemotherapy for colon cancer: advancing prognosis, toxicity prediction, and dose personalization.Frontiers in pharmacology · 2026Review
- Ergothioneine Attenuates Oxaliplatin-Induced Peripheral Neuropathy Without Compromising Antitumor Efficacy.International journal of molecular sciences · 2025Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Small-molecule natural product sophoricoside reduces peripheral neuropathic pain via directly blocking of NaV1.6 in dorsal root ganglion nociceptive neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Identification of a signature gene set for oxaliplatin sensitivity prediction in colorectal cancer.Frontiers in oncology · 2025Article
- Resurgent current in context: Insights from the structure and function of Na and K channels.Biophysical journal · 2024Review
- Article
- Targeting therapy-induced senescence as a novel strategy to combat chemotherapy-induced peripheral neuropathy.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Review
58 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Infusion of the chemotherapeutic agent oxaliplatin leads to an acute and a chronic form of peripheral neuropathy. Acute oxaliplatin neuropathy is characterized by sensory paresthesias and muscle cramps that are notably exacerbated by cooling. Painful dysesthesias are rarely reported for acute oxaliplatin neuropathy, whereas a common symptom of chronic oxaliplatin neuropathy is pain. Here we examine the role of the sodium channel isoform Na(V)1.6 in mediating the symptoms of acute oxaliplatin neuropathy. Compound and single-action potential recordings from human and mouse peripheral axons showed that cooling in the presence of oxaliplatin (30-100 μM; 90 min) induced bursts of action potentials in myelinated A, but not unmyelinated C-fibers. Whole-cell patch-clamp recordings from dissociated dorsal root ganglion (DRG) neurons revealed enhanced tetrodotoxin-sensitive resurgent and persistent current amplitudes in large, but not small, diameter DRG neurons when cooled (22 °C) in the presence of oxaliplatin. In DRG neurons and peripheral myelinated axons from Scn8a(med/med) mice, which lack functional Na(V)1.6, no effect of oxaliplatin and cooling was observed. Oxaliplatin significantly slows the rate of fast inactivation at negative potentials in heterologously expressed mNa(V)1.6r in ND7 cells, an effect consistent with prolonged Na(V) open times and increased resurgent and persistent current in native DRG neurons. This finding suggests that Na(V)1.6 plays a central role in mediating acute cooling-exacerbated symptoms following oxaliplatin, and that enhanced resurgent and persistent sodium currents may provide a general mechanistic basis for cold-aggravated symptoms of neuropathy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.