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

  title={DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons},
  author={Jian-Yuan Zhao and Lingli Liang and Xiyao Gu and Zhisong Li and Shaogen Wu and Linlin Sun and Fidelis E. Atianjoh and Jian Feng and Kai Mo and Shushan Jia and Brianna Marie Lutz and Alex Y. Bekker and Eric J. Nestler and Yuan-Xiang Tao},
  journal={Nature Communications},
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… 

Contribution of DNMT1 to Neuropathic Pain Genesis Partially through Epigenetically Repressing Kcna2 in Primary Afferent Neurons

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Nerve injury–induced epigenetic silencing of opioid receptors controlled by DNMT3a in primary afferent neurons

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Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury

Findings indicate that octamer transcription factor 1 may participate in neuropathic pain at least in part by transcriptionally activating Dnmt3a and subsequently epigenetic silencing of Oprm1 and Kcan2 in the DRG and may serve as a potential target for therapeutic treatments against neuropathicPain.

TET1 Overexpression Mitigates Neuropathic Pain Through Rescuing the Expression of μ-Opioid Receptor and Kv1.2 in the Primary Sensory Neurons

Findings suggest that DRG TET1 overexpression mitigated neuropathic pain likely through rescue of MOR and Kv1.2 expression in the ipsilateral DRG.

A nerve injury–specific long noncoding RNA promotes neuropathic pain by increasing Ccl2 expression

NIS-lncRNA participates in neuropathic pain likely by promoting FUS-triggered DRG Ccl2 expression and may be a potential target in neuropathy pain management.

MMP24 Contributes to Neuropathic Pain in an FTO-Dependent Manner in the Spinal Cord Neurons

SNL promoted the m6A eraser FTO binding to the Mmp24 mRNA, which subsequently facilitated the translation of MMP24 in the spinal cord, and ultimately contributed to neuropathic pain genesis.



G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory neurons

It is shown that blocking nerve injury-induced increase in G9a rescued Kcna2 mRNA and protein expression in the axotomized DRG and attenuated the development of nerve Injury-induced pain hypersensitivity.

Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma

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A long noncoding RNA contributes to neuropathic pain by silencing Kcna2 in primary afferent neurons

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The findings indicate that G9a contributes critically to transcriptional repression of MORs in primary sensory neurons in neuropathic pain and may be used to enhance the opioid analgesic effect in the treatment of chronic neuropathicPain.

Epigenetic Gene Silencing Underlies C-Fiber Dysfunctions in Neuropathic Pain

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Increased methylation of the MOR gene proximal promoter in primary sensory neurons plays a crucial role in the decreased analgesic effect of opioids in neuropathic pain

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Expression of DNA methyltransferases in adult dorsal root ganglia is cell-type specific and up regulated in a rodent model of neuropathic pain

It is suggested that DNMT regulation in adult DRGs may be a contributor to the pain phenotype and merits further study.

G9a Is Essential for Epigenetic Silencing of K+ Channel Genes in Acute-to-Chronic Pain Transition

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, suggesting that G 9a has a dominant function in transcriptional repression of K- channels and in acute-to-chronic pain transition after nerve injury.

Downregulation of voltage-gated potassium channel alpha gene expression by axotomy and neurotrophins in rat dorsal root ganglia.

The findings suggest that downregulation of Kv channel gene expression in DRG neurons by neurotrophins may play an important role in long-term changes of neuronal excitability following nerve injury.