ArticleThe Journal of biological chemistry2014
The development and maintenance of paclitaxel-induced neuropathic pain require activation of the sphingosine 1-phosphate receptor subtype 1.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 156 citations in OpenAlex.
- Genomewide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy.Clinical pharmacology and therapeutics · 2020Pooled it
- Ketotifen for Preventing Oxaliplatin-Induced Neuropathy in Stage III Colorectal Cancer: a Randomized Controlled Trial.Journal of gastrointestinal cancer · 2026Trial
- Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Trial
- Using an integrated omics approach to uncover the mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN).Communications medicine · 2026Review
- The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Mechanisms and treatment of cancer therapy-induced peripheral and central neurotoxicity.Nature reviews. Cancer · 2025Review
- Sphingosine-1-Phosphate Signaling through Müller Glia Regulates Neuroprotection, Accumulation of Immune Cells, and Neuronal Regeneration in the Rodent Retina.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- S1P receptor 1 antagonist ponesimod alleviates postherpetic neuralgia in rats by normalizing spinal TRPV1 expression and inhibiting MAPK-mediated glial activation.Cytotechnology · 2025Article
- Addressing the Needs of Breast Cancer Survivors.Current oncology reports · 2025Review
- Article
- Investigation of the Effect of Rose Oxide in Animal Models of Paclitaxel-induced Neuropathic Pain in Rats.Current pharmaceutical design · 2025Article
- Innate immunity in chemotherapy-induced peripheral neuropathy: recent advances.Frontiers in pain research (Lausanne, Switzerland) · 2025Review
- Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.Frontiers in pharmacology · 2025Review
- Suppression of Paclitaxel-Induced Neuropathy and Ovarian Tumor Growth by Mn Porphyrin, MnTnBuOE-2-PyPOxidative medicine and cellular longevity · 2025Article
- Dissociation between the anti-allodynic effects of fingolimod (FTY720) and desensitization of S1PNeuropharmacology · 2024Article
- Involvement of sphingosine-1-phosphate receptor 1 in pain insensitivity in a BTBR mouse model of autism spectrum disorder.BMC medicine · 2024Article
- Article
- FTY720/Fingolimod mitigates paclitaxel-induced Sparcl1-driven neuropathic pain and breast cancer progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- HDAC inhibitors as a potential therapy for chemotherapy-induced neuropathic pain.Inflammopharmacology · 2024Review
- The correlation between vitamin D and the occurrence of peripheral neuropathy induced by paclitaxel chemotherapy.Frontiers in medicine · 2024Article
27 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
17 authors at 8 institutions in 2 countries.
Funding
Abstract
The ceramide-sphingosine 1-phosphate (S1P) rheostat is important in regulating cell fate. Several chemotherapeutic agents, including paclitaxel (Taxol), involve pro-apoptotic ceramide in their anticancer effects. The ceramide-to-S1P pathway is also implicated in the development of pain, raising the intriguing possibility that these sphingolipids may contribute to chemotherapy- induced painful peripheral neuropathy, which can be a critical dose-limiting side effect of many widely used chemotherapeutic agents.We demonstrate that the development of paclitaxel-induced neuropathic pain was associated with ceramide and S1P formation in the spinal dorsal horn that corresponded with the engagement of S1P receptor subtype 1 (S1PR(1))- dependent neuroinflammatory processes as follows: activation of redox-sensitive transcription factors (NFκB) and MAPKs (ERK and p38) as well as enhanced formation of pro-inflammatory and neuroexcitatory cytokines (TNF-α and IL-1β). Intrathecal delivery of the S1PR1 antagonist W146 reduced these neuroinflammatory processes but increased IL-10 and IL-4, potent anti-inflammatory/ neuroprotective cytokines. Additionally, spinal W146 reversed established neuropathic pain. Noteworthy, systemic administration of the S1PR1 modulator FTY720 (Food and Drug Administration- approved for multiple sclerosis) attenuated the activation of these neuroinflammatory processes and abrogated neuropathic pain without altering anticancer properties of paclitaxel and with beneficial effects extended to oxaliplatin. Similar effects were observed with other structurally and chemically unrelated S1PR1 modulators (ponesimod and CYM-5442) and S1PR1 antagonists (NIBR-14/15) but not S1PR1 agonists (SEW2871). Our findings identify for the first time the S1P/S1PR1 axis as a promising molecular and therapeutic target in chemotherapy-induced painful peripheral neuropathy, establish a mechanistic insight into the biomolecular signaling pathways, and provide the rationale for the clinical evaluation of FTY720 in chronic pain patients.
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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.