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.

FEBS Open Bio
|October 9, 2015
PubMed

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.