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Published on: October 10, 2025
MicroRNAs downregulated in neuropathic pain regulate MeCP2 and BDNF related to pain sensitivity
Melissa T Manners1, Yuzhen Tian1, Zhaolan Zhou2
1Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, USA.
Abstract:
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.
Insights
Nerve injury alters microRNAs and methyl-CpG-binding protein 2 (MECP2) in dorsal root ganglia, affecting pain sensitivity. MECP2 and brain-derived neurotrophic factor (BDNF) interactions in DRG may modulate chronic pain.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Nerve injury leads to chronic pain and microRNA changes in dorsal root ganglia (DRG).
- Downregulated microRNAs after nerve injury are predicted to target methyl-CpG-binding protein 2 (MECP2).
- MECP2 mutations are linked to Rett syndrome, characterized by altered pain perception.
Purpose of the Study:
- To investigate the role of MECP2 in DRG following nerve injury.
- To explore the relationship between MECP2, microRNAs, and brain-derived neurotrophic factor (BDNF) in pain modulation.
Main Methods:
- Confirmation of MECP2 upregulation in DRG post-nerve injury.
- In vitro studies on microRNA-mediated repression of MECP2 and its effect on BDNF.
- Analysis of pain sensitivity and BDNF levels in Mecp2-mutant mice (Mecp2-null and T158A).
Main Results:
- MeCP2 was upregulated in DRG after nerve injury.
- MicroRNAs downregulated MECP2 and subsequently decreased BDNF expression in vitro.
- Mecp2-null and MeCP2 T158A mice showed reduced mechanical sensitivity and lower BDNF levels in DRG.
Conclusions:
- MeCP2 upregulation in DRG following nerve injury.
- MeCP2-mediated regulation of BDNF in DRG contributes to altered pain sensitivity.
- This pathway is a potential target for managing chronic pain.

