Nature communications, 2017-03, Vol.8 (1), p.14712-14712, Article 14712
2017
Details
- Autor(en) / Beteiligte
- Titel
- DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons
- Ist Teil von
- Nature communications, 2017-03, Vol.8 (1), p.14712-14712, Article 14712
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/ncomms14712Titel-ID: cdi_doaj_primary_oai_doaj_org_article_6546e90f8d0a479b8916bd70184ce7f5
- Format
- –
- Schlagworte
- Anesthesiology, Animals, Central Nervous System Sensitization - genetics, Deoxyribonucleic acid, Disease Models, Animal, DNA, DNA (Cytosine-5-)-Methyltransferases - genetics, DNA methylation, DNA methyltransferase, Dorsal root ganglia, Epigenetics, Excitability, Ganglia, Spinal - cytology, Gene expression, Gene Expression Regulation, Genetic engineering, Injury prevention, Kv1.2 Potassium Channel - genetics, Kv1.2 Potassium Channel - metabolism, Ligation, Male, Mimicry, Neuralgia - genetics, Neurons, Neurons, Afferent - metabolism, Neurosciences, Octamer Transcription Factor-1 - genetics, Pain, Peripheral Nerve Injuries - genetics, Peripheral nerves, Peripheral neuropathy, Potassium, Potassium channels (voltage-gated), Proteins, Rats, Sensory neurons, Spinal cord, Spinal Nerves - injuries, Surgery, Transcription activation, Transcription factors