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Target Concepts:
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Query: UMLS:C0184567 (
acute pain
)
3,962
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 MBD1 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.
SIGNIFICANCE STATEMENT
In the present study, we revealed that the mice with deficiency of methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, in the DRG displayed the reduced responses to acute noxious stimuli and the blunted neuropathic pain. We also showed that DRG overexpression of MBD1 produced the hypersensitivities to noxious stimuli in the WT mice and rescued
acute pain
sensitivities in the MBD1-deficient mice. We have also provided the evidence that MDB1 represses
Oprm1
and
Kcna2
gene expression by recruiting
DNA methyltransferase
DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 may participate in the genesis of
acute pain
and neuropathic pain likely through regulating DNMT3a-controlled
Oprm1
and
Kcna2
gene expression in the DRG neurons.
...
PMID:MBD1 Contributes to the Genesis of Acute Pain and Neuropathic Pain by Epigenetic Silencing of
Oprm1
and
Kcna2
Genes in Primary Sensory Neurons. 3026 39
