Evidence map›Paper›PMID 28270689›Full record

ArticleNature communications2017

DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons.

Jian-Yuan Zhao, Lingli Liang, Xiyao Gu, Zhisong Li, Shaogen Wu, Linlin Sun, Fidelis E Atianjoh, Jian Feng, Kai Mo, Shushan Jia and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
12.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

129 citing papers in PubMed, 227 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. RNA-binding protein MBNL2 mitigates neuropathic pain after chemotherapy through destabilizing CCR2 expression in primary sensory neurons.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  7. Article
  8. Review
  9. 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 · 2026
    Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. The Role of Methylation Modification in Neural Injury and Repair.International journal of molecular sciences · 2025
    Review
  17. Article
  18. Article
  19. DNMT3a Downregulation Ttriggered Upregulation of GABAAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  20. Article

69 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Jian-Yuan ZhaoDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Lingli LiangDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Xiyao GuDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Zhisong LiDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Shaogen WuDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Linlin SunDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Fidelis E AtianjohDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Jian FengFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Kai MoDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Shushan JiaDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Brianna Marie LutzDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Alex BekkerDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Eric J NestlerFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Yuan-Xiang TaoDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.
Rutgers, The State University of New Jersey · USIcahn School of Medicine at Mount Sinai · USFirst Affiliated Hospital of Zhengzhou University · CN

Funding

TRANSGENIC COREP01DA008227 · NIDA · YALE UNIVERSITY · PI NESTLER, ERIC J. · 1993 to 2018
$28.1M
REPRESSIVE HISTONE AND DNA METHYLATION IN RODENT DEPRESSION MODELSP50MH096890 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ALLIS, CHARLES DAVID · 2012 to 2021
$20.2M
The Role of Endothelin-1 in Sickle Cell DiseaseU01HL117684 · NHLBI · AUGUSTA UNIVERSITY · PI KUTLAR, ABDULLAH, MEILER, STEFFEN · 2013 to 2017
$8.1M
Dissection of a new spinal cord circuit in pain sensationR01NS094224 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI LUO, WENQIN · 2016 to 2020
$2.5M
Epigenetic regulation of neuropathic pain: Role of DRG histone methyltransferase G9aR01NS094664 · NINDS · RBHS-NEW JERSEY MEDICAL SCHOOL · PI TAO, YUAN-XIANG · 2016 to 2020
$2.0M
mTOR, a new target for opioid-induced tolerance and hyperalgesiaR01DA033390 · NIDA · RBHS-NEW JERSEY MEDICAL SCHOOL · PI TAO, YUAN-XIANG · 2013 to 2017
$1.8M
Epigenetic Regulation of Neuropathic Pain: Role of Native Kv1.2 Antisense RNAR01NS072206 · NINDS · RBHS-NEW JERSEY MEDICAL SCHOOL · PI TAO, YUAN-XIANG · 2011 to 2014
$1.4M
Role of BK Channel Interactome in Excessive Ethanol DrinkingU01AA020913 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI CONTET, CANDICE · 2011 to 2015
$1.3M
Epigenetic mechanism of nerve injury-induced Kv1.2 downregulation in DRG neuronsF31NS092310 · NINDS · RBHS-NEW JERSEY MEDICAL SCHOOL · PI LUTZ, BRIANNA M. · 2015 to 2017
$89k
NHLBI NIH HHS U01 HL117684NIAAA NIH HHS U01 AA020913NIDA NIH HHS P01 DA008227NIDA NIH HHS R01 DA033390NIMH NIH HHS P50 MH096890NINDS NIH HHS F31 NS092310NINDS NIH HHS R01 NS072206NINDS NIH HHS R01 NS094224NINDS NIH HHS R01 NS094664
6 · The paper itself

Abstract

Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain. Conversely, in the absence of nerve injury, mimicking this increase reduces the Kcna2 promoter activity, diminishes Kcna2 expression, decreases Kv current, increases excitability in DRG neurons and leads to spinal cord central sensitization and neuropathic pain symptoms. These findings suggest that DNMT3a may contribute to neuropathic pain by repressing Kcna2 expression in the DRG.

Indexed as

AnimalsCentral Nervous System SensitizationDisease Models, AnimalDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AGanglia, SpinalGene Expression RegulationKv1.2 Potassium ChannelLigationMaleNeuralgiaNeurons, AfferentOctamer Transcription Factor-1Peripheral Nerve InjuriesRatsSpinal NervesDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AKcna2 protein, ratKv1.2 Potassium ChannelOctamer Transcription Factor-1

Identifiers

PMID28270689
PMCPMC5344974
OpenAlexW2592581800

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.