ArticleThe journal of pain2019
Activation of Sphingosine-1-Phosphate Receptor 1 in the Spinal Cord Produces Mechanohypersensitivity Through the Activation of Inflammasome and IL-1β Pathway.
Article in The journal of pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Nanoformulated fingolimod attenuates NLRP3 inflammasome activation and promotes functional recovery in a rat model of spinal cord injury.Spinal cord · 2026Article
- Cry2 deficiency leads to cognitive impairment through the microbiota-gut-brain axis mediated S1P/NLRP3/IL-1β pathway in mice.Journal of neuroinflammation · 2026Article
- Context-Dependent Roles of Four Classes of Bioactive Lipids in Neuroglia-Mediated Regulation of Neuroinflammation.Journal of pain research · 2025Review
- Dissociation between the anti-allodynic effects of fingolimod (FTY720) and desensitization of S1PNeuropharmacology · 2024Article
- 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
- Dysregulation of sphingolipid metabolism in pain.Frontiers in pharmacology · 2024Review
- Sphingosine 1-phosphate receptor 1 regulates blood-brain barrier permeability in epileptic mice.Neural regeneration research · 2023Article
- The NLRP3 inflammasome: role in the pathobiology of chronic pain.Inflammopharmacology · 2023Review
- Role of Adenosine Kinase in Sphingosine-1-Phosphate Receptor 1-Induced Mechano-Hypersensitivities.Cellular and molecular neurobiology · 2022Article
- Sphingosine-1-phosphate receptor 1 activation in the central nervous system drives cisplatin-induced cognitive impairment.The Journal of clinical investigation · 2022Article
- S1PR1 regulates NDV-induced IL-1β expression via NLRP3/caspase-1 inflammasome.Veterinary research · 2022Article
- Sphingosine-1 phosphate receptor 1 contributes to central sensitization in recurrent nitroglycerin-induced chronic migraine model.The journal of headache and pain · 2022Article
- Glial Cells and Brain Diseases: Inflammasomes as Relevant Pathological Entities.Frontiers in cellular neuroscience · 2022Review
- Dysregulation in Sphingolipid Signaling Pathways is Associated With Symptoms and Functional Connectivity of Pain Processing Brain Regions in Provoked Vestibulodynia.The journal of pain · 2021Observational
- S1P/S1PAntioxidants (Basel, Switzerland) · 2021Article
- Early-life fingolimod treatment improves intestinal homeostasis and pancreatic immune tolerance in non-obese diabetic mice.Acta pharmacologica Sinica · 2021Article
- The Modulatory Effect of Motor Cortex Astrocytes on Diabetic Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Vincristine- and bortezomib-induced neuropathies - from bedside to bench and back.Experimental neurology · 2021Review
- Targeting the Sphingosine-1-Phosphate Axis for Developing Non-narcotic Pain Therapeutics.Trends in pharmacological sciences · 2020Review
- Sphingosine-1-phosphate receptor subtype 1 activation in the central nervous system contributes to morphine withdrawal in rodents.Journal of neuroinflammation · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Sphingosine-1-phosphate (S1P) receptor 1 subtype (S1PR1) activation by its ligand S1P in the dorsal horn of the spinal cord causes mechanohypersensitivity. The cellular and molecular pathways remain poorly understood. We report that the activation of S1PR1 with an intrathecal injection of the highly selective S1PR1 agonist SEW2871 led to the development of mechanoallodynia by activating the nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome (increased expression of NLRP3, cleaved caspase 1 and mature IL-1β) in the dorsal horn of the spinal cord. The functional S1PR1 antagonist FTY720 blocked NLRP3 activation and IL-1β production. Moreover, inhibiting IL-10 signaling with an intrathecal injection of an anti-IL-10 antibody attenuated the beneficial effects exerted by FTY720. This finding suggests that disrupting S1PR1 signaling engages beneficial IL-10-dependent pathways. Notably, we found that mice with astrocyte-specific deletions of S1pr1 did not develop mechanoallodynia after intrathecal injection of SEW2871 and exhibited decreased levels of cleaved caspase 1, identifying astrocytes as a key cellular locus for S1PR1 activity. Our findings provide novel mechanistic insights on how S1PR1 activation in the spinal cord contributes to the development of nociception while identifying the cellular substrate for these activities. PERSPECTIVE: This study is the first to link the activation of NLRP3 and IL-1β signaling in the spinal cord and S1PR1 signaling in astrocytes to the development of S1PR1-evoked mechanoallodynia. These findings provide critical basic science insights to support the development of therapies targeted toward S1PR1.
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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.