ArticleScientific reports2016
A novel P2X4 receptor-selective antagonist produces anti-allodynic effect in a mouse model of herpetic pain.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 2 of them syntheses that pooled it.
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Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 127 citations in OpenAlex.
- Neuropathic pain in burn patients - A common problem with little literature: A systematic review.Burns : journal of the International Society for Burn Injuries · 2024Pooled it
- The core of maintaining neuropathic pain: Crosstalk between glial cells and neurons (neural cell crosstalk at spinal cord).Brain and behavior · 2023Pooled it
- P2X4 Receptor Antagonists Exert Anti-Inflammatory Effects via NLRP3 Inflammasome in a Murine Model of Colitis.ACS pharmacology & translational science · 2026Article
- Novel P2X4 Receptor Antagonist MRS4719 Improves Ischemia/reperfusion Injury in Mice.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Aberrant alternative splicing of purinergic receptor P2RX4 prevents sensitivity towards combinatorial treatment in colorectal and pancreatic cancer.The Journal of pathology · 2026Article
- Kainate-induced ATP release contributes to spinal excitotoxicity that is attenuated by purinergic blockade.Frontiers in neurology · 2026Article
- Glial Activation, Neuroinflammation, and Loss of Neuroprotection in Chronic Pain: Cellular Mechanisms and Emerging Therapeutic Strategies.Biomedicines · 2025Review
- Discovery of an allosteric binding site for anthraquinones at the human P2X4 receptor.Nature communications · 2025Article
- Sex differences in phenotypic modulation of microglia by early-life physical stress in a rat model of chronic primary low back pain.Pflugers Archiv : European journal of physiology · 2025Article
- Depletion of P2X4 receptor alleviates prostate cancer bone metastasis through reduced cancer cell invasiveness and enhanced cell adhesion activities.Purinergic signalling · 2025Article
- Review
- Novel role for purinergic 2× subtype 4 (P2X4) receptors in the exercise pressor reflex and mechanoreflex: Effect of heart failure.Autonomic neuroscience : basic & clinical · 2025Article
- Article
- Species Differences of P2X4 Receptor Modulators.ACS pharmacology & translational science · 2025Article
- Article
- Preparation and preliminary evaluation of a tritium-labeled allosteric P2X4 receptor antagonist.Purinergic signalling · 2024Article
- Pharmacology of P2X Receptors and Their Possible Therapeutic Potential in Obesity and Diabetes.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Daphnetin Ameliorates Neuropathic Pain via Regulation of Microglial Responses and Glycerophospholipid Metabolism in the Spinal Cord.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Microglia in Neuropathic Pain.Advances in neurobiology · 2024Review
- Microglial P2X4 receptors are essential for spinal neurons hyperexcitability and tactile allodynia in male and female neuropathic mice.iScience · 2023Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence indicates that purinergic P2X4 receptors (P2X4R: cation channels activated by extracellular ATP) expressed in spinal microglia are crucial for pathological chronic pain caused by nerve damage, suggesting a potential target for drug discovery. We identified NP-1815-PX (5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1, 2-b][1,4]diazepine-2,4(3H,5H)-dione) as a novel antagonist selective for P2X4R with high potency and selectivity compared with other P2XR subtypes. In in vivo assay for acute and chronic pain, intrathecal administration of NP-1815-PX produced an anti-allodynic effect in mice with traumatic nerve damage without affecting acute nociceptive pain and motor function (although its oral administration did not produce the effect). Furthermore, in a mouse model of herpetic pain, P2X4R upregulation in the spinal cord exclusively occurred in microglia, and intrathecal NP-1815-PX suppressed induction of mechanical allodynia. This model also showed K(+)/Cl(-) cotransporter 2 (KCC2) downregulation, which is implicated in dorsal horn neuron hyperexcitability; this downregulation was restored by intrathecal treatment with NP-1815-PX or by interfering with brain-derived neurotrophic factor (BDNF) signaling, a P2X4R-activated microglial factor implicated in KCC2 downregulation. Taken together, the newly developed P2X4R antagonist NP-1815-PX produces anti-allodynic effects in chronic pain models without altering acute pain sensitivity, suggesting that microglial P2X4R could be an attractive target for treating chronic pain.
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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.