ArticleScience advances2023
ATP-releasing SWELL1 channel in spinal microglia contributes to neuropathic pain.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 87 citations in OpenAlex.
- State-dependent inhibition of LRRC8 volume-regulated anion channels by DCPIB.The Journal of general physiology · 2026Article
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- The intracellular subdomain of the volume-regulated anion channel subunit LRRC8A is a hotspot of channel activation.Nature communications · 2026Article
- Structures of the volume-regulated anion channel LRRC8A/D in activating and inhibiting conditions.Nature communications · 2026Article
- Neuromodulation Techniques Alleviating Neuropathic Pain by Targeting Microglia: A Narrative Review.Pain and therapy · 2026Review
- Energy Homeostasis Disruption in Neurological Disorders: Mitochondrial Dysfunction, High-Energy Phosphate Transfer, and Extracellular ATP-Dependent Purinergic Dysregulation.International journal of molecular sciences · 2026Review
- Microglial SWELL1 deficiency drives male-specific seizure vulnerability but paradoxical neuroprotection through impaired phagocytosis.JCI insight · 2026Article
- Endothelial LRRC8C Associates With LRRC8A and LRRC8B to Regulate Vascular Reactivity and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Mechanism of action of two potent LRRC8/VRAC channel inhibitors.Research square · 2026Article
- Metabolite-neuro-immune relay in chronic pain: spatial-temporal lactate, succinate and itaconate signalling as drivers of glial reprogramming and neuronal sensitisation.Frontiers in pharmacology · 2026Review
- Exploring the selective inhibitory effects of Flavoxate and its analogues on two chloride channels and neuronal action potentials.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Review
- Puromycin-sensitive aminopeptidase acts as an inhibitory auxiliary subunit of volume-regulated anion channels and regulates cGAMP transport.Molecular cell · 2025Article
- LRRC8A Regulates Outer Hair Cell Volume and Electromotility and is Required for Hearing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The chloride intracellular channel 1 (CLIC1) is essential for microglial morphodynamics and neuroinflammation.Science advances · 2025Article
- LRRC8A constitutively inhibits pain hypersensitivity in rodent models by restraining NMDA receptor activity at spinal cord synapses.Science translational medicine · 2025Article
- A conserved mechanism of LRRC8 channel inhibition by two structurally distinct drugs.Communications biology · 2025Article
- Beyond inflammation: a comprehensive microglial regulation model in chronic pain.Molecular biology reports · 2025Review
- LRRC8 complexes are ATP release channels that regulate platelet activation and arterial thrombosis.Blood · 2025Article
- Puromycin-sensitive aminopeptidase acts as an inhibitory auxiliary subunit of volume-regulated anion channels.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Following peripheral nerve injury, extracellular adenosine 5'-triphosphate (ATP)-mediated purinergic signaling is crucial for spinal cord microglia activation and neuropathic pain. However, the mechanisms of ATP release remain poorly understood. Here, we show that volume-regulated anion channel (VRAC) is an ATP-releasing channel and is activated by inflammatory mediator sphingosine-1-phosphate (S1P) in microglia. Mice with microglia-specific deletion of Swell1 (also known as Lrrc8a), a VRAC essential subunit, had reduced peripheral nerve injury-induced increase in extracellular ATP in spinal cord. The mutant mice also exhibited decreased spinal microgliosis, dorsal horn neuronal hyperactivity, and both evoked and spontaneous neuropathic pain-like behaviors. We further performed high-throughput screens and identified an FDA-approved drug dicumarol as a novel and potent VRAC inhibitor. Intrathecal administration of dicumarol alleviated nerve injury-induced mechanical allodynia in mice. Our findings suggest that ATP-releasing VRAC in microglia is a key spinal cord determinant of neuropathic pain and a potential therapeutic target for this debilitating disease.
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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.