ArticleProceedings of the National Academy of Sciences of the United States of America2019
Sphingosine-1-phosphate receptor 1 activation in astrocytes contributes to neuropathic pain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.
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Who cites it
74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 128 citations in OpenAlex.
- Individual participant data meta-analysis of metabolomics on sustained knee pain in primary osteoarthritis patients.Rheumatology (Oxford, England) · 2023Pooled it
- Genomewide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy.Clinical pharmacology and therapeutics · 2020Pooled it
- Effects of Selective Sphingosine-1-Phosphate Receptor 1 Agonist, TRV045, on Evoked Pain Tests: An Exploratory, Four-Way Cross-Over Study in Healthy Volunteers.European journal of pain (London, England) · 2026Trial
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Inflammatory neuropathy in mouse and primate models of colorectal cancer.Nature communications · 2026Article
- Article
- Treatment effects on sphingosine-1-phosphate and its receptors in major depressive disorder: implications for biomarkers.BMC psychiatry · 2026Article
- Glial cells in chronic inflammation: diversity, dysfunction and therapeutic targeting.Nature reviews. Immunology · 2026Review
- Spinal Cord Stimulation Alleviates Neuropathic Pain Involves Regulation of the CaCellular and molecular neurobiology · 2026Article
- Sphingosine-1-Phosphate Receptor 1 regulates competition dependent astrocyte morphogenesis and tiling in murine cortex.bioRxiv : the preprint server for biology · 2026Article
- The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Neuroplasticity-Driven Mechanisms and Therapeutic Targets in the Anterior Cingulate Cortex in Neuropathic Pain.Brain and behavior · 2026Review
- S1PR4 connects cancer pain to pan-cancer mechanisms and reveals prognosis, immune infiltration and therapeutic potential.Discover oncology · 2026Article
- Exosomes: Roles and Therapeutic Potential in Pain.Biomedicines · 2026Review
- Role of astrocytes in diabetic neuropathy: Review of their involvement in disease mechanisms.World journal of diabetes · 2025Review
- S1P receptor 1 antagonist ponesimod alleviates postherpetic neuralgia in rats by normalizing spinal TRPV1 expression and inhibiting MAPK-mediated glial activation.Cytotechnology · 2025Article
- Metabolism of sphingolipids in a rat spinal cord stenosis model.Biochemistry and biophysics reports · 2025Article
- The Inflammasome-miR Axis in Alzheimer's Disease and Chronic Pain: Molecular Mechanisms and Therapeutic Opportunities.Aging and disease · 2025Review
- Sex Differences in the Regulation of Interleukins in Chronic Pain: A Widely Recognized but Difficult-to-Tackle Factor.International journal of molecular sciences · 2025Review
- Context-Dependent Roles of Four Classes of Bioactive Lipids in Neuroglia-Mediated Regulation of Neuroinflammation.Journal of pain research · 2025Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Neuropathic pain afflicts millions of individuals and represents a major health problem for which there is limited effective and safe therapy. Emerging literature links altered sphingolipid metabolism to nociceptive processing. However, the neuropharmacology of sphingolipid signaling in the central nervous system in the context of chronic pain remains largely unexplored and controversial. We now provide evidence that sphingosine-1-phosphate (S1P) generated in the dorsal horn of the spinal cord in response to nerve injury drives neuropathic pain by selectively activating the S1P receptor subtype 1 (S1PR1) in astrocytes. Accordingly, genetic and pharmacological inhibition of S1PR1 with multiple antagonists in distinct chemical classes, but not agonists, attenuated and even reversed neuropathic pain in rodents of both sexes and in two models of traumatic nerve injury. These S1PR1 antagonists retained their ability to inhibit neuropathic pain during sustained drug administration, and their effects were independent of endogenous opioid circuits. Moreover, mice with astrocyte-specific knockout of
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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.