ArticlePain2017
Targeting the S1P/S1PR1 axis mitigates cancer-induced bone pain and neuroinflammation.
Article in Pain, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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The trial behind it
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- Elevated 18:1 lysophosphatidylcholine contributes to neuropathic pain in peripheral nerve injury.Regional anesthesia and pain medicine · 2026Article
- Mesenchymal stem cell therapy for premature ovarian insufficiency: progress and challenges.Journal of ovarian research · 2026Review
- Mechanism of BMSCs Inhibiting Microglia Activation and Neuroinflammatory Response to Alleviate BCP by Regulating TLR4/ NF-κB Signaling Pathway.Journal of inflammation research · 2026Article
- The protective role of Lactobacillus reuteri in a DSS-induced ulcerative colitis mouse model.PloS one · 2025Article
- Innate immunity in chemotherapy-induced peripheral neuropathy: recent advances.Frontiers in pain research (Lausanne, Switzerland) · 2025Review
- Sphingosine 1-phosphate receptor 1 modulators exert neuroprotective effects in central nervous system disorders.Frontiers in pharmacology · 2025Review
- Dissociation between the anti-allodynic effects of fingolimod (FTY720) and desensitization of S1PNeuropharmacology · 2024Article
- Article
- Dysregulation of sphingolipid metabolism in pain.Frontiers in pharmacology · 2024Review
- Evaluation of pain related behaviors and disease related outcomes in an immunocompetent mouse model of prostate cancer induced bone pain.Journal of bone oncology · 2023Article
- Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells.Cancers · 2023Review
- Crosstalk of Mast Cells and Natural Killer Cells with Neurons in Chemotherapy-Induced Peripheral Neuropathy.International journal of molecular sciences · 2023Review
- Management of cancer pain due to bone metastasis.Journal of bone and mineral metabolism · 2023Review
- Activation of the STING pathway induces peripheral sensitization via neuroinflammation in a rat model of bone cancer pain.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Role of Adenosine Kinase in Sphingosine-1-Phosphate Receptor 1-Induced Mechano-Hypersensitivities.Cellular and molecular neurobiology · 2022Article
- Review
- Lipidomic Profiling Identifies Serum Lipids Associated with Persistent Multisite Musculoskeletal Pain.Metabolites · 2022Article
- Sphingosine-1 phosphate receptor 1 contributes to central sensitization in recurrent nitroglycerin-induced chronic migraine model.The journal of headache and pain · 2022Article
- A Method of Bone-Metastatic Tumor Progression Assessment in Mice Using Longitudinal Radiography.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Metastatic bone pain is the single most common form of cancer pain and persists as a result of peripheral and central inflammatory, as well as neuropathic mechanisms. Here, we provide the first characterization of sphingolipid metabolism alterations in the spinal cord occurring during cancer-induced bone pain (CIBP). Following femoral arthrotomy and syngenic tumor implantation in mice, ceramides decreased with corresponding increases in sphingosine and the bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P). Intriguingly, de novo sphingolipid biosynthesis was increased as shown by the elevations of dihydro-ceramides and dihydro-S1P. We next identified the S1P receptor subtype 1 (S1PR1) as a novel target for therapeutic intervention. Intrathecal or systemic administration of the competitive and functional S1PR1 antagonists, TASP0277308 and FTY720/Fingolimod, respectively, attenuated cancer-induced spontaneous flinching and guarding. Inhibiting CIBP by systemic delivery of FTY720 did not result in antinociceptive tolerance over 7 days. FTY720 administration enhanced IL-10 in the lumbar ipsilateral spinal cord of CIBP animals and intrathecal injection of an IL-10 neutralizing antibody mitigated the ability of systemic FTY720 to reverse CIBP. FTY720 treatment was not associated with alterations in bone metabolism in vivo. Studies here identify a novel mechanism to inhibit bone cancer pain by blocking the actions of the bioactive metabolites S1P and dihydro-S1P in lumbar spinal cord induced by bone cancer and support potential fast-track clinical application of the FDA-approved drug, FTY720, as a therapeutic avenue for CIBP.
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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.