MeCP2 Epigenetic Silencing of Oprm1 Gene in Primary Sensory Neurons Under Neuropathic Pain Conditions

• DOI: 10.3389/fnins.2021.743207
• Publication Date: 2021-11-05T10:37:02Z
• Authors: Na Sun; Lina Yu; Yibo Gao; Longfei Ma; Jinxuan Ren; Ying Liu; Dave Schwinn Gao; Chen Xie; Ying Wu; Lieju Wang; Juncong Hong; Min Yan
• Keywords: MeCP2; HDAC1; Dorsal root ganglion

Opioids are the last option for pharmacological treatment of neuropathic pain, but their antinociceptive effects limited. Decreased mu opioid receptor (MOR) expression in peripheral nervous system may contribute to this. Here, we showed that nerve injury induced hypermethylation Oprm1 gene promoter and an increased methyl-CpG binding protein 2 (MeCP2) injured dorsal root ganglion (DRG). The downregulation MOR DRG is closely related augmentation MeCP2, epigenetic repressor, which could recruit HDAC1 bind methylated regions promoter. MeCP2 knockdown restored enhanced analgesic effect morphine, while mimicking this increase via intrathecal infusion viral vector-mediated was sufficient reduce DRG. Moreover, inhibition with suberoylanilide hydroxamic acid, HDAC inhibitor, also prevented reduction pain mice, contributing morphine analgesia effects. Mechanistically, upregulated promotes a high level HDCA1 hypermethylated promoter, reduces acetylation histone H3 (acH3) levels attenuates transcription Thus, sites, negatively regulates DRG, mitigating opioids. Targeting MeCP2/HDAC1 thus provide new solution improving therapeutic opioids clinical setting.