MicroRNAs downregulated in neuropathic pain regulate MeCP2 and BDNF related to pain sensitivity

• MeCP2 is upregulated in the dorsal root ganglia (DRG) from a spared nerve injury model of neuropathic pain.
• miR-19a- and miR-301-mediated regulation of MeCP2 resulted in Bdnf alteration.
• MeCP2 T158A mice have decreased mechanical sensitivity.
• Bdnf is downregulated in the DRG in Mecp2-null mice and MeCP2 T158A mice.

Nerve injury induces chronic pain and dysregulation of microRNAs in dorsal root ganglia (DRG). Several downregulated microRNAs are predicted to target Mecp2. MECP2 mutations cause Rett syndrome and these patients report decreased pain perception. We confirmed MeCP2 upregulation in DRG following nerve injury and repression of MeCP2 by miRNAs in vitro. MeCP2 regulates brain-derived neurotrophic factor (BDNF) and downregulation of MeCP2 by microRNAs decreased Bdnf in vitro. MeCP2 T158A mice exhibited reduced mechanical sensitivity and Mecp2-null and MeCP2 T158A mice have decreased Bdnf in DRG. MeCP2-mediated regulation of Bdnf in the DRG could contribute to altered pain sensitivity.