期刊
JOURNAL OF NEUROSCIENCE
卷 38, 期 46, 页码 9883-9899出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0880-18.2018
关键词
acute pain; DRG; Kv1.2; MBD1; mu opioid receptor; neuropathic pain
资金
- National Institutes of Health [R01NS094664, R01NS094224, R01DA033390]
- Natural Science Foundation of Guangdong Province in China [2017A030313599]
- Southern Medical University in China Young Scientist and Technician Training Program [PY2016N014]
The transmission of normal sensory and/or acute noxious information requires intact expression of pain-associated genes within the pain pathways of nervous system. Expressional changes of these genes after peripheral nerve injury are also critical for neuropathic pain induction and maintenance. Methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, regulates gene transcriptional activity. We report here that MBDI in the primary sensory neurons of DRG is critical for the genesis of acute pain and neuropathic pain as DRG MBD1-deficient mice exhibit the reduced responses to acute mechanical, heat, cold, and capsaicin stimuli and the blunted nerve injury-induced pain hypersensitivities. Furthermore, DRG overexpression of MBD1 leads to spontaneous pain and evoked pain hypersensitivities in the WT mice and restores acute pain sensitivities in the MBD1 -deficient mice. Mechanistically, MDB1 represses Oprm1 and Kcna2 gene expression by recruiting DNA methyltransferase DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 is likely a key player under the conditions of acute pain and neuropathic pain.
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