ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Functional downregulation of P2X3 receptor subunit in rat sensory neurons reveals a significant role in chronic neuropathic and inflammatory pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 256 citations in OpenAlex.
- Identification and validation of MicroRNA-mRNA Networks in Dorsal Root Ganglia after Peripheral Nerve Injury.International journal of medical sciences · 2022Pooled it
- Induced Pluripotent Stem Cell-Based Platforms for Cardiac-Related Pain Research: Molecular Mechanisms, Experimental Models, and Therapeutic Applications.International journal of molecular sciences · 2026Review
- Spinal P2XPurinergic signalling · 2026Article
- Cdk5 modulates orofacial pain through P2X2/3 purinergic receptor-mediated signaling in trigeminal neurons.Frontiers in pharmacology · 2026Article
- Endogenous forms of ATP-ATPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The exploration of active components of 701 Dieda Zhentong patch and analgesic properties on chronic constriction injury rats.Purinergic signalling · 2025Article
- Advances in Therapeutic Applications of CRISPR Genome Editing for Spinal Pain Management.Neurospine · 2025Article
- The Orphan Receptor GPR151: Discovery, Expression, and Emerging Biological Significance.ACS chemical neuroscience · 2025Review
- Potent painkiller from spider venom antagonizes P2X3 receptors without dysgeusia.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Electroacupuncture alleviates neuropathic pain in a rat model of CCD via suppressing P2X3 expression in dorsal root ganglia.Chinese medicine · 2024Article
- Role of spinal astrocytes through the perisynaptic astrocytic process in pathological pain.Molecular brain · 2023Review
- Future directions for medicinal chemistry in the field of oligonucleotide therapeutics.RNA (New York, N.Y.) · 2023Article
- Polyphyllin VI screened from Chonglou by cell membrane immobilized chromatography relieves inflammatory pain by inhibiting inflammation and normalizing the expression of P2XFrontiers in pharmacology · 2023Article
- The Role of ATP Receptors in Pain Signaling.Neurochemical research · 2022Review
- Systemic DNA/RNA heteroduplex oligonucleotide administration for regulating the gene expression of dorsal root ganglion and sciatic nerve.Molecular therapy. Nucleic acids · 2022Article
- Synthesis and Structure-Activity Relationship Studies of Benzimidazole-4,7-dione-Based P2X3 Receptor Antagonists as Novel Anti-Nociceptive Agents.Molecules (Basel, Switzerland) · 2022Article
- Single-cell transcriptomic analysis of somatosensory neurons uncovers temporal development of neuropathic pain.Cell research · 2021Article
- Single-cell transcriptomic analysis of somatosensory neurons uncovers temporal development of neuropathic pain.Cell research · 2021Article
- Review
- Nociceptive signaling of P2X receptors in chronic pain states.Purinergic signalling · 2021Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The excitation of nociceptive sensory neurons by ATP released in injured tissue is believed to be mediated partly by P2X3 receptors. Although an analysis of P2X3 knock-out mice has revealed some deficits in nociceptive signaling, detailed analysis of the role of these receptors is hampered by the lack of potent specific pharmacological tools. Here we have used antisense oligonucleotides (ASOs) to downregulate P2X3 receptors to examine their role in models of chronic pain in the rat. ASOs and control missense oligonucleotides (180 microg/d) were administered intrathecally to naive rats for up to 7 d via a lumbar indwelling cannula attached to an osmotic minipump. Functional downregulation of the receptors was confirmed by alphabeta-methylene ATP injection into the hindpaw, which evoked significantly less mechanical hyperalgesia as early as 2 d after treatment with ASOs relative to controls. At this time point, P2X3 protein levels were significantly downregulated in lumbar L4 and L5 dorsal root ganglia. After 7 d of ASO treatment, P2X3 protein levels were reduced in the primary afferent terminals in the lumbar dorsal horn of the spinal cord. In models of neuropathic (partial sciatic ligation) and inflammatory (complete Freund's adjuvant) pain, inhibition of the development of mechanical hyperalgesia as well as significant reversal of established hyperalgesia were observed within 2 d of ASO treatment. The time course of the reversal of hyperalgesia is consistent with downregulation of P2X3 receptor protein and function. This study demonstrates the utility of ASO approaches for validating gene targets in in vivo pain models and provides evidence for a role of P2X3 receptors in the pathophysiology of chronic pain.
Indexed as
Identifiers
12223568PMC6758070W1697474905What 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.