ArticlePain2015
Prevention of chemotherapy-induced peripheral neuropathy by the small-molecule inhibitor pifithrin-μ.
Article in Pain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 82 citations in OpenAlex.
- Neural-tumor interactions: bidirectional regulatory mechanisms and nervous system-targeted tumor therapeutic strategies.Biomarker research · 2026Review
- ILP4 and InR regulate paclitaxel-induced hypersensitivity differently inMolecular biology of the cell · 2026Article
- Emerging targets and translational challenges in treating paclitaxel-induced peripheral neuropathy.Molecular biology reports · 2025Review
- RNA splicing modulator for Huntington's disease treatment induces peripheral neuropathy.iScience · 2025Article
- Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases.Current issues in molecular biology · 2025Review
- Identification and Validation of Antidepressant Small Molecules Using Bioinformatics and Mouse Depression Models.Drug design, development and therapy · 2025Article
- Pifithrin-µ Induces Stress Granule Formation, Regulates Cell Survival, and Rewires Cellular Signaling.Cells · 2024Article
- Upregulation of NGF/TrkA-Related Proteins in Dorsal Root Ganglion of Paclitaxel-Induced Peripheral Neuropathy Animal Model.Journal of pain research · 2024Article
- Targeting the Main Sources of Reactive Oxygen Species Production: Possible Therapeutic Implications in Chronic Pain.Current neuropharmacology · 2024Review
- Intranasally Administered MSC-Derived Extracellular Vesicles Reverse Cisplatin-Induced Cognitive Impairment.International journal of molecular sciences · 2023Article
- Oxaliplatin-induced peripheral neurotoxicity in colorectal cancer patients: mechanisms, pharmacokinetics and strategies.Frontiers in pharmacology · 2023Review
- PGC1α: an emerging therapeutic target for chemotherapy-induced peripheral neuropathy.Therapeutic advances in neurological disorders · 2023Review
- Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials.Nature medicine · 2023Article
- Sensory neuron dysfunction in orthotopic mouse models of colon cancer.Journal of neuroinflammation · 2022Article
- Targeting the Meningeal Compartment to Resolve Chemobrain and Neuropathy via Nasal Delivery of Functionalized Mitochondria.Advanced healthcare materials · 2022Article
- A mechanistic understanding of the relationship between skin innervation and chemotherapy-induced neuropathic pain.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Alleviation of cisplatin-induced neuropathic pain, neuronal apoptosis, and systemic inflammation in mice by rapamycin.Frontiers in aging neuroscience · 2022Article
- Cutaneous pain in disorders affecting peripheral nerves.Neuroscience letters · 2021Review
- Nasal administration of mesenchymal stem cells reverses chemotherapy-induced peripheral neuropathy in mice.Brain, behavior, and immunity · 2021Article
- Development of a novel in vitro assay to screen for neuroprotective drugs against iatrogenic neurite shortening.PloS one · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. It is the most frequent cause of dose reduction or treatment discontinuation in patients treated for cancer with commonly used drugs including taxanes and platinum-based compounds. No FDA-approved treatments for CIPN are available. In rodents, CIPN is represented by peripheral mechanical allodynia in association with retraction of intraepidermal nerve fibers. The mechanism of chemotherapy-induced neurotoxicity is unclear, but it has been established that mitochondrial dysfunction is an important component of the dysregulation in peripheral sensory neurons. We have shown earlier that inhibition of mitochondrial p53 accumulation with the small compound pifithrin-μ (PFT-μ) prevents cerebral neuronal death in a rodent model of hypoxic-ischemic brain damage. We now explore whether PFT-μ is capable of preventing neuronal mitochondrial damage and CIPN in mice. We demonstrate for the first time that PFT-μ prevents both paclitaxel- and cisplatin-induced mechanical allodynia. Electron microscopic analysis of peripheral sensory nerves revealed that PFT-μ secured mitochondrial integrity in paclitaxel-treated mice. In addition, PFT-μ administration protects against chemotherapy-induced loss of intraepidermal nerve fibers in the paw. To determine whether neuroprotective treatment with PFT-μ would interfere with the antitumor effects of chemotherapy, ovarian tumor cells were cultured in vitro with PFT-μ and paclitaxel. Pifithrin-μ does not inhibit tumor cell death but even enhances paclitaxel-induced tumor cell death. These data are the first to identify PFT-μ as a potential therapeutic strategy for prevention of CIPN to combat one of the most devastating side effects of chemotherapy.
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Registered trials
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.