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- Title
Contribution of DNMT1 to Neuropathic Pain Genesis Partially through Epigenetically Repressing Kcna2 in Primary Afferent Neurons.
- Authors
Linlin Sun; Xiyao Gu; Zhiqiang Pan; Xinying Guo; Jianbin Liu; Atianjoh, Fidelis E.; Shaogen Wu; Kai Mo; Bo Xu; Lingli Liang; Bekker, Alex; Yuan-Xiang Tao
- Abstract
Expressional changes of pain-associated genes in primary sensory neurons of DRG are critical for neuropathic pain genesis. DNA methyltransferase (DNMT)-triggered DNA methylation silences gene expression. We show here that DNMT1, a canonical maintenance methyltransferase, acts as the de novo DNMT and is required for neuropathic pain genesis likely through repressing at least DRG Kcna2 gene expression in male mice. Peripheral nerve injury upregulated DNMT1 expression in the injured DRG through the transcription factor cAMP response element binding protein-triggered transcriptional activation of Dnmtl gene. Blocking this upregulation prevented nerve injury-induced DNA methylation within the promoter and 5'-untranslated region of Kcna2 gene, rescued Kcna2 expression and total Kv current, attenuated hyperexcitability in the injured DRG neurons, and alleviated nerve injury-induced pain hypersensitivities. Given that Kcna2 is a key player in neuropathic pain, our findings suggest that DRG DNMT 1 may be a potential target for neuropathic pain management.
- Subjects
DNA methyltransferases; GENE silencing; SENSORY neurons; DNA methylation; PAIN management
- Publication
Journal of Neuroscience, 2019, Vol 39, Issue 33, p6595
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/jneurosci.0695-19.2019