Trial reportThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Sphingosine-1-phosphate-induced nociceptor excitation and ongoing pain behavior in mice and humans is largely mediated by S1P3 receptor.
Trial report in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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
36 citing papers in PubMed, 64 citations in OpenAlex.
- Metabolism of sphingolipids in a rat spinal cord stenosis model.Biochemistry and biophysics reports · 2025Article
- Sphingosine phosphate lyase insufficiency syndrome as a primary immunodeficiency state.Advances in biological regulation · 2024Review
- Lipid Alterations in Chronic Nonspecific Low Back Pain in the Chinese Population: A Metabolomic and Lipidomic Study.Bioengineering (Basel, Switzerland) · 2024Article
- Dysregulation of sphingolipid metabolism in pain.Frontiers in pharmacology · 2024Review
- The Sphingosine 1-Phosphate Axis: an Emerging Therapeutic Opportunity for Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- The SphK1/S1P Axis Regulates Synaptic Vesicle Endocytosis via TRPC5 Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The FKBP51 Inhibitor SAFit2 Restores the Pain-Relieving C16 Dihydroceramide after Nerve Injury.International journal of molecular sciences · 2022Article
- Review
- Targeting the Sphingosine-1-Phosphate Axis for Developing Non-narcotic Pain Therapeutics.Trends in pharmacological sciences · 2020Review
- Role of TRP Channels in Shaping the Gut Microbiome.Pathogens (Basel, Switzerland) · 2020Article
- Selected Ionotropic Receptors and Voltage-Gated Ion Channels: More Functional Competence for Human Induced Pluripotent Stem Cell (iPSC)-Derived Nociceptors.Brain sciences · 2020Article
- Chloride - The Underrated Ion in Nociceptors.Frontiers in neuroscience · 2020Review
- Sphingosine-1-phosphate activates mouse vagal airway afferent C-fibres via S1PR3 receptors.The Journal of physiology · 2019Article
- A nervous S1P of the lung: activation of airway nerves by sphingosine-1-phosphate.The Journal of physiology · 2019Article
- Impaired mechanical, heat, and cold nociception in a murine model of genetic TACE/ADAM17 knockdown.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- S1PR3 Mediates Itch and Pain via Distinct TRP Channel-Dependent Pathways.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Differential Tolerance to FTY720-Induced Antinociception in Acute Thermal and Nerve Injury Mouse Pain Models: Role of Sphingosine-1-Phosphate Receptor Adaptation.The Journal of pharmacology and experimental therapeutics · 2018Article
- Itch suppression in mice and dogs by modulation of spinal α2 and α3GABANature communications · 2018Article
- Article
- Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory ClFrontiers in molecular neuroscience · 2018Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 5 countries.
Funding
Abstract
The biolipid sphingosine-1-phosphate (S1P) is an essential modulator of innate immunity, cell migration, and wound healing. It is released locally upon acute tissue injury from endothelial cells and activated thrombocytes and, therefore, may give rise to acute post-traumatic pain sensation via a yet elusive molecular mechanism. We have used an interdisciplinary approach to address this question, and we find that intradermal injection of S1P induced significant licking and flinching behavior in wild-type mice and a dose-dependent flare reaction in human skin as a sign of acute activation of nociceptive nerve terminals. Notably, S1P evoked a small excitatory ionic current that resulted in nociceptor depolarization and action potential firing. This ionic current was preserved in "cation-free" solution and blocked by the nonspecific Cl(-) channel inhibitor niflumic acid and by preincubation with the G-protein inhibitor GDP-β-S. Notably, S1P(3) receptor was detected in virtually all neurons in human and mouse DRG. In line with this finding, S1P-induced neuronal responses and spontaneous pain behavior in vivo were substantially reduced in S1P(3)(-/-) mice, whereas in control S1P(1) floxed (S1P(1)(fl/fl)) mice and mice with a nociceptor-specific deletion of S1P(1)(-/-) receptor (SNS-S1P(1)(-/-)), neither the S1P-induced responses in vitro nor the S1P-evoked pain-like behavior was altered. Therefore, these findings indicate that S1P evokes significant nociception via G-protein-dependent activation of an excitatory Cl(-) conductance that is largely mediated by S1P(3) receptors present in nociceptors, and point to these receptors as valuable therapeutic targets for post-traumatic pain.
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What OpenQuestion holds
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.