ArticleNature neuroscience2015
G9a is essential for epigenetic silencing of K(+) channel genes in acute-to-chronic pain transition.
Article in Nature neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
What it found
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Who cites it
125 citing papers in PubMed, 193 citations in OpenAlex.
- Sensory neuron BRAF mediates opioid-induced hyperalgesia and tolerance via presynaptic NMDA receptor hyperactivity.The Journal of clinical investigation · 2026Article
- Shared Genetic Architecture and Multidimensional Modifiable Correlates between Myopia and Retinal-Optic Nerve Diseases.Ophthalmology science · 2026Article
- Epigenetic Mechanisms in Perioperative Medicine: From Neuroinflammation and NETosis to Organ Dysfunction and Precision Therapeutics.Biomedicines · 2026Review
- Ribonuclease 4 Functions in Nociceptor-Mediated Nerve Homeostasis.Nature communications · 2026Article
- Homeostatic preservation of action potential waveform by Notch and Nerfin-1.Current biology : CB · 2026Article
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Histone Lactylation Contributes to Neuropathic Pain by Facilitating mThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Dorsal Root Ganglion as a Hub for Peripheral Sensitization: A Hierarchical Regulation Model and Translational Progress.Journal of pain research · 2026Review
- Incision-triggered neuroimmune remodeling of nociceptor ion channels: from postoperative inflammation to pain chronification.Frontiers in immunology · 2026Review
- Epigenetic, chromatin-associated, and epitranscriptomic regulation in chronic pain: mechanisms and translational prospects.Frontiers in genetics · 2026Review
- Tonic GABA and Glycine Inhibition Control Pain Hypersensitivity via Limiting α2δ-1- and mGluR5-Dependent NMDA Receptor Activity at Primary Afferent→Excitatory Neuron Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- LRRC8A constitutively inhibits pain hypersensitivity in rodent models by restraining NMDA receptor activity at spinal cord synapses.Science translational medicine · 2025Article
- Targeting neurodegeneration: three machine learning methods for G9a inhibitors discovery using PubChem and scikit-learn.Journal of computer-aided molecular design · 2025Article
- The Role of Methylation Modification in Neural Injury and Repair.International journal of molecular sciences · 2025Review
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- Article
- Histone Methyltransferase G9a in Primary Sensory Neurons Promotes Inflammatory Pain and Transcription ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- H3K27 Trimethylation-Mediated Downregulation of miR-216a-3p in Sensory Neurons Regulates Neuropathic Pain Behaviors via Targeting STIM1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Upregulation of delta opioid receptor by meningeal interleukin-10 prevents relapsing pain.Brain, behavior, and immunity · 2025Article
- Regulation of Kv1.2 Redox-Sensitive Gating by the Transmembrane Lectin LMAN2.Function (Oxford, England) · 2024Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Neuropathic pain is a debilitating clinical problem and difficult to treat. Nerve injury causes a long-lasting reduction in K(+) channel expression in the dorsal root ganglion (DRG), but little is known about the epigenetic mechanisms involved. We found that nerve injury increased dimethylation of Lys9 on histone H3 (H3K9me2) at Kcna4, Kcnd2, Kcnq2 and Kcnma1 promoters but did not affect levels of DNA methylation on these genes in DRGs. Nerve injury increased activity of euchromatic histone-lysine N-methyltransferase-2 (G9a), histone deacetylases and enhancer of zeste homolog-2 (EZH2), but only G9a inhibition consistently restored K(+) channel expression. Selective knockout of the gene encoding G9a in DRG neurons completely blocked K(+) channel silencing and chronic pain development after nerve injury. Remarkably, RNA sequencing analysis revealed that G9a inhibition not only reactivated 40 of 42 silenced genes associated with K(+) channels but also normalized 638 genes down- or upregulated by nerve injury. Thus G9a has a dominant function in transcriptional repression of K(+) channels and in acute-to-chronic pain transition after nerve injury.
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What 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.