ArticleProceedings of the National Academy of Sciences of the United States of America2008
Activation of P2X7 receptors in glial satellite cells reduces pain through downregulation of P2X3 receptors in nociceptive neurons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 148 citations in OpenAlex.
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Electroacupuncture and P2X receptors: purinergic mechanisms in pain modulation : A narrative review with structured evidence mapping.Purinergic signalling · 2026Review
- Satellite Glial Cells in Peripheral Nerve Injury and Regeneration.Biomedicines · 2026Review
- Targeting glial-orchestrated neuroinflammation in migraine pathophysiology.The journal of headache and pain · 2026Review
- Type II Cells in the Human Carotid Body Display P2X7 Receptor and Pannexin-1 Immunoreactivity.Biomolecules · 2025Article
- P2X7 and P2YPurinergic signalling · 2025Article
- Regulatory role of electroacupuncture on satellite glial cell activity in the colon and dorsal root ganglion of rats with irritable bowel syndrome.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Peripheral gating of mechanosensation by glial diazepam binding inhibitor.The Journal of clinical investigation · 2024Article
- P2X7 receptors and pannexin1 hemichannels shape presynaptic transmission.Purinergic signalling · 2024Review
- Dissociation and Culture of Adult Mouse Satellite Glial Cells.Bio-protocol · 2023Article
- Glia Signaling and Brain Microenvironment in Migraine.Molecular neurobiology · 2023Review
- The Similar and Distinct Roles of Satellite Glial Cells and Spinal Astrocytes in Neuropathic Pain.Cells · 2023Review
- Spinal cord astrocyte P2X7Rs mediate the inhibitory effect of electroacupuncture on visceral hypersensitivity of rat with irritable bowel syndrome.Purinergic signalling · 2023Article
- Purinergic signaling: a potential therapeutic target for depression and chronic pain.Purinergic signalling · 2023Review
- Activation of GDNF-ERK-Runx1 signaling contributes to P2X3R gene transcription and bone cancer pain.iScience · 2022Article
- BzATP Activates Satellite Glial Cells and Increases the Excitability of Dorsal Root Ganglia Neurons In Vivo.Cells · 2022Article
- Fibroblastic SMOC2 Suppresses Mechanical Nociception by Inhibiting Coupled Activation of Primary Sensory Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Involvement of P2X7 receptors in chronic pain disorders.Purinergic signalling · 2022Review
- Comparative transcriptional analysis of satellite glial cell injury response.Wellcome open research · 2022Article
- Satellite Glial Cells: Morphology, functional heterogeneity, and role in pain.Frontiers in cellular neuroscience · 2022Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purinergic ionotropic P2X7 receptors (P2X7Rs) are closely associated with excitotoxicity and nociception. Inhibition of P2X7R activation has been considered as a potentially useful strategy to improve recovery from spinal cord injury and reduce inflammatory damage to trauma. The physiological functions of P2X7Rs, however, are poorly understood, even though such information is essential for making the P2X7R an effective therapeutic target. We show here that P2X7Rs in satellite cells of dorsal root ganglia tonically inhibit the expression of P2X3Rs in neurons. Reducing P2X7R expression using siRNA or blocking P2X7R activity by antagonists elicits P2X3R up-regulation, increases the activity of sensory neurons responding to painful stimuli, and evokes abnormal nociceptive behaviors in rats. Thus, contrary to the notion that P2X7R activation is cytotoxic, P2X7Rs in satellite cells play a crucial role in maintaining proper P2X3R expression in dorsal root ganglia. Studying the mechanism underlying the P2X7R-P2X3R control, we demonstrate that activation of P2X7Rs evokes ATP release from satellite cells. ATP in turn stimulates P2Y1 receptors in neurons. P2Y1 receptor activation appears to be necessary and sufficient for the inhibitory control of P2X3R expression. We further determine the roles of the P2X7R-P2Y1-P2X3R inhibitory control under injurious conditions. Activation of the inhibitory control effectively prevents the development of allodynia and increases the potency of systemically administered P2X7R agonists in inflamed rats. Thus, direct blocking P2X7Rs, as proposed before, may not be the best strategy for reducing pain or lessening neuronal degeneration because it also disrupts the protective function of P2X7Rs.
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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.