ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Targeting the overproduction of peroxynitrite for the prevention and reversal of paclitaxel-induced neuropathic pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.
- Preclinical research in paclitaxel-induced neuropathic pain: a systematic review.Frontiers in veterinary science · 2023Pooled it
- Trial
- The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Site-specific drug release of monomethyl fumarate to treat oxidative stress disorders.Nature biotechnology · 2025Article
- Astrocytic Inducible Nitric Oxide Synthase Upregulation Contributes to Chronic Below-Level Neuropathic Pain Following Spinal Cord Injury in Male Rats.European journal of pain (London, England) · 2025Article
- Astrocyte elevated gene-1 (AEG-1) in myeloid cells is a key driver for the development of chemotherapy-induced peripheral neuropathy.Brain, behavior, and immunity · 2025Article
- MnTBAP, a peroxynitrite scavenger, attenuates cisplatin-induced apoptosis and cytotoxicity in organ of Corti cells.Toxicology reports · 2025Article
- Nitroxidative Stress, Cell-Signaling Pathways, and Manganese Porphyrins: Therapeutic Potential in Neuropathic Pain.International journal of molecular sciences · 2025Review
- Suppression of Paclitaxel-Induced Neuropathy and Ovarian Tumor Growth by Mn Porphyrin, MnTnBuOE-2-PyPOxidative medicine and cellular longevity · 2025Article
- Mechanisms and Management of Albumin-Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer.Breast cancer (Dove Medical Press) · 2025Review
- Evaluation and application analysis of animal models of PIPNP based on data mining.Open life sciences · 2025Review
- Differential effect of targeting cisplatin-induced nitrative stress using MnTBAP in auditory and cancer cells.Current research in toxicology · 2025Article
- Exploring the Role of Bergamot Polyphenols in Alleviating Morphine-Induced Hyperalgesia and Tolerance through Modulation of Mitochondrial SIRT3.Nutrients · 2024Article
- Manganese- and Platinum-Driven Oxidative and Nitrosative Stress in Oxaliplatin-Associated CIPN with Special Reference to CaInternational journal of molecular sciences · 2024Review
- Molecular and Cellular Involvement in CIPN.Biomedicines · 2024Review
- Role of pattern recognition receptors in chemotherapy-induced neuropathic pain.Brain : a journal of neurology · 2024Article
- αO-Conotoxin GeXIVA[1,2] Reduced Neuropathic Pain and Changed Gene Expression in Chronic Oxaliplatin-Induced Neuropathy Mice Model.Marine drugs · 2024Article
- 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
- Peripheral neurotoxicity induced by albumin-bound paclitaxel: a case report.Frontiers in oncology · 2024Article
- The correlation between vitamin D and the occurrence of peripheral neuropathy induced by paclitaxel chemotherapy.Frontiers in medicine · 2024Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) accompanied by chronic neuropathic pain is a major dose-limiting side effect of a large number of antitumoral agents including paclitaxel (Taxol). Thus, CIPN is one of most common causes of dose reduction and discontinuation of what is otherwise a life-saving therapy. Neuropathological changes in spinal cord are linked to CIPN, but the causative mediators and mechanisms remain poorly understood. We report that formation of peroxynitrite (PN) in response to activation of nitric oxide synthases and NADPH oxidase in spinal cord contributes to neuropathological changes through two mechanisms. The first involves modulation of neuroexcitatory and proinflammatory (TNF-α and IL-1β) and anti-inflammatory (IL-10 and IL-4) cytokines in favor of the former. The second involves post-translational nitration and modification of glia-derived proteins known to be involved in glutamatergic neurotransmission (astrocyte-restricted glutamate transporters and glutamine synthetase). Targeting PN with PN decomposition catalysts (PNDCs) not only blocked the development of paclitaxel-induced neuropathic pain without interfering with antitumor effects, but also reversed it once established. Herein, we describe our mechanistic study on the role(s) of PN and the prevention of neuropathic pain in rats using known PNDCs (FeTMPyP(5+) and MnTE-2-PyP(5+)). We also demonstrate the prevention of CIPN with our two new orally active PNDCs, SRI6 and SRI110. The improved chemical design of SRI6 and SRI110 also affords selectivity for PN over other reactive oxygen species (such as superoxide). Our findings identify PN as a critical determinant of CIPN, while providing the rationale toward development of superoxide-sparing and "PN-targeted" therapeutics.
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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.