ZBTB20 regulates nociception and pain sensation by modulating TRP channel expression in nociceptive sensory neurons

Nat Commun. 2014 Nov 5;5:4984. doi: 10.1038/ncomms5984.

Abstract

In mammals, pain sensation is initiated by the detection of noxious stimuli through specialized transduction ion channels and receptors in nociceptive sensory neurons. Transient receptor potential (TRP) channels are the key sensory transducers that confer nociceptors distinct sensory modalities. However, the regulatory mechanisms about their expression are poorly defined. Here we show that the zinc-finger protein ZBTB20 regulates TRP channels expression in nociceptors. ZBTB20 is highly expressed in nociceptive sensory neurons of dorsal root ganglia. Disruption of ZBTB20 in nociceptors led to a marked decrease in the expression levels of TRPV1, TRPA1 and TRPM8 and the response of calcium flux and whole-cell currents evoked by their respective specific agonists. Phenotypically, the mice lacking ZBTB20 specifically in nociceptors showed a defect in nociception and pain sensation in response to thermal, mechanical and inflammatory stimulation. Our findings point to ZBTB20 as a critical regulator of nociception and pain sensation by modulating TRP channels expression in nociceptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nociception*
  • Nociceptors / metabolism*
  • TRPA1 Cation Channel
  • TRPM Cation Channels / genetics*
  • TRPM Cation Channels / metabolism
  • TRPV Cation Channels / genetics*
  • TRPV Cation Channels / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transient Receptor Potential Channels / genetics*
  • Transient Receptor Potential Channels / metabolism

Substances

  • TRPA1 Cation Channel
  • TRPM Cation Channels
  • TRPM8 protein, mouse
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Transcription Factors
  • Transient Receptor Potential Channels
  • Trpa1 protein, mouse
  • Zbtb20 protein, mouse