ArticleJournal of neuroinflammation2019
TNF-α/STAT3 pathway epigenetically upregulates Nav1.6 expression in DRG and contributes to neuropathic pain induced by L5-VRT.
Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 88 citations in OpenAlex.
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- Leuprolide Acetate Promotes Sensory Recovery and Modulates Dorsal Root Ganglion Responses After Sciatic Nerve Transection in Rats.Brain sciences · 2026Article
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- Shaping the Action Potential in Dorsal Root and Trigeminal Ganglia Neurons: Relevance to Pain Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- TNF-α-preconditioning enhances analgesic efficacy of mesenchymal stem cell-derived extracellular vesicle in neuropathic painBioactive materials · 2025Article
- Spinocerebellar Ataxia 27 A with Episodic Ataxia: Case Series of Fibroblast Growth Factor 14 (FGF14) Microdeletions.Cerebellum (London, England) · 2025Article
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- Marine-derived bioactive compounds for neuropathic pain: pharmacology and therapeutic potential.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Emerging role of macrophages in neuropathic pain.Journal of orthopaedic translation · 2025Review
- Unveiling the Mechanisms of Pain in Endometriosis: Comprehensive Analysis of Inflammatory Sensitization and Therapeutic Potential.International journal of molecular sciences · 2025Review
- P300-Targeted Acetylome Reveals a Role for HMGB1 Translocation in Central Cardiac Sympathetic Activation Post Myocardial Infarction.Journal of inflammation research · 2025Article
- Exosomal TNF-α mediates voltage-gated Na+ channel 1.6 overexpression and contributes to brain tumor-induced neuronal hyperexcitability.The Journal of clinical investigation · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- TNFR1 signaling converging on FGF14 controls neuronal hyperactivity and sickness behavior in experimental cerebral malaria.Journal of neuroinflammation · 2023Article
- The Epigenetics of Neuropathic Pain: A Systematic Update.International journal of molecular sciences · 2023Review
- Upregulation of lysine-specific demethylase 6B aggravates inflammatory pain through H3K27me3 demethylation-dependent production of TNF-α in the dorsal root ganglia and spinal dorsal horn in rats.CNS neuroscience & therapeutics · 2023Article
- Article
- Role of the voltage‑gated sodium channel Nav1.6 in glioma and candidate drugs screening.International journal of molecular medicine · 2023Article
- CXCL13 contributes to chronic pain of a mouse model of CRPS-I via CXCR5-mediated NF-κB activation and pro-inflammatory cytokine production in spinal cord dorsal horn.Journal of neuroinflammation · 2023Article
- SUMOylation of Kir7.1 participates in neuropathic pain through regulating its membrane expression in spinal cord neurons.CNS neuroscience & therapeutics · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStudies showed that upregulation of Nav1.6 increased the neuronal excitability and participated in neuropathic pain in the dorsal root ganglion (DRG). However, the molecular mechanisms underlying Nav1.6 upregulation were not reported yet.
methodsThe paw withdrawal threshold was measured in the rodents following lumbar 5 ventral root transection (L5-VRT). Then qPCR, western blotting, immunoprecipitation, immunohistochemistry, and chromatin immunoprecipitation assays were performed to explore the molecular mechanisms in vivo and in vitro.
resultsWe found that the levels of Nav1.6 and phosphorylated STAT3 were significantly increased in DRG neurons following L5-VRT, and TNF-α incubation also upregulated the Nav1.6 expression in cultured DRG neurons. Furthermore, immunoprecipitation and chromatin immunoprecipitation assays demonstrated that L5-VRT increased the binding of STAT3 to the Scn8a (encoding Nav1.6) promoter and the interaction between STAT3 and p300, which contributed to the enhanced transcription of Scn8a by increasing histone H4 acetylation in Scn8a promoter in DRG. Importantly, intraperitoneal injection of the TNF-α inhibitor thalidomide reduced the phosphorylation of STAT3 and decreased the recruitment of STAT3 and histone H4 hyperacetylation in the Scn8a promoter, thus subsequently attenuating Nav1.6 upregulation in DRG neurons and mechanical allodynia induced by L5-VRT.
conclusionThese results suggested a new mechanism for Nav1.6 upregulation involving TNF-α/STAT3 pathway activation and subsequent STAT3-mediated histone H4 hyperacetylation in the Scn8a promoter region in DRG, which contributed to L5-VRT-induced neuropathic pain.
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