MicroRNA cluster miR-17-92 regulates multiple functionally related voltage-gated potassium channels in chronic neuropathic pain

Nat Commun. 2017 Jul 5:8:16079. doi: 10.1038/ncomms16079.


miR-17-92 is a microRNA cluster with six distinct members. Here, we show that the miR-17-92 cluster and its individual members modulate chronic neuropathic pain. All cluster members are persistently upregulated in primary sensory neurons after nerve injury. Overexpression of miR-18a, miR-19a, miR-19b and miR-92a cluster members elicits mechanical allodynia in rats, while their blockade alleviates mechanical allodynia in a rat model of neuropathic pain. Plausible targets for the miR-17-92 cluster include genes encoding numerous voltage-gated potassium channels and their modulatory subunits. Single-cell analysis reveals extensive co-expression of miR-17-92 cluster and its predicted targets in primary sensory neurons. miR-17-92 downregulates the expression of potassium channels, and reduced outward potassium currents, in particular A-type currents. Combined application of potassium channel modulators synergistically alleviates mechanical allodynia induced by nerve injury or miR-17-92 overexpression. miR-17-92 cluster appears to cooperatively regulate the function of multiple voltage-gated potassium channel subunits, perpetuating mechanical allodynia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines
  • Animals
  • Chronic Pain / etiology
  • Chronic Pain / metabolism*
  • Down-Regulation
  • Ganglia, Spinal / metabolism
  • Hyperalgesia / etiology
  • Hyperalgesia / metabolism*
  • Male
  • MicroRNAs / metabolism*
  • Neuralgia / etiology
  • Neuralgia / metabolism*
  • Neurons / metabolism
  • Phenylurea Compounds
  • Potassium Channels, Voltage-Gated / metabolism*
  • Rats, Sprague-Dawley
  • Tetrazoles


  • 1-(3,5-bis-trifluoromethylphenyl)-3-(2,4-dibromo-6-(1H-tetrazol-5-yl)phenyl)urea
  • Aminopyridines
  • MicroRNAs
  • Phenylurea Compounds
  • Potassium Channels, Voltage-Gated
  • Tetrazoles
  • flupirtine