miR-183 cluster scales mechanical pain sensitivity by regulating basal and neuropathic pain genes

Science. 2017 Jun 16;356(6343):1168-1171. doi: 10.1126/science.aam7671. Epub 2017 Jun 1.

Abstract

Nociception is protective and prevents tissue damage but can also facilitate chronic pain. Whether a general principle governs these two types of pain is unknown. Here, we show that both basal mechanical and neuropathic pain are controlled by the microRNA-183 (miR-183) cluster in mice. This single cluster controls more than 80% of neuropathic pain-regulated genes and scales basal mechanical sensitivity and mechanical allodynia by regulating auxiliary voltage-gated calcium channel subunits α2δ-1 and α2δ-2. Basal sensitivity is controlled in nociceptors, and allodynia involves TrkB+ light-touch mechanoreceptors. These light-touch-sensitive neurons, which normally do not elicit pain, produce pain during neuropathy that is reversed by gabapentin. Thus, a single microRNA cluster continuously scales acute noxious mechanical sensitivity in nociceptive neurons and suppresses neuropathic pain transduction in a specific, light-touch-sensitive neuronal type recruited during mechanical allodynia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Gene Expression Regulation / genetics*
  • Mechanoreceptors / physiology
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neuralgia / genetics*
  • Nociceptors / physiology
  • Pain / genetics*

Substances

  • Calcium Channels
  • MicroRNAs
  • Mirn183 microRNA, mouse