Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1.

Published

Journal Article

Intracellular microRNAs (miRNAs) are key regulators of gene expression. The role of extracellular miRNAs in neuronal activation and sensory behaviors are unknown. Here we report an unconventional role of extracellular miRNAs for rapid excitation of nociceptor neurons via toll-like receptor-7 (TLR7) and its coupling to TRPA1 ion channel. miRNA-let-7b induces rapid inward currents and action potentials in dorsal root ganglion (DRG) neurons. These responses require the GUUGUGU motif, only occur in neurons coexpressing TLR7 and TRPA1, and are abolished in mice lacking Tlr7 or Trpa1. Furthermore, let-7b induces TLR7/TRPA1-dependent single-channel activities in DRG neurons and HEK293 cells overexpressing TLR7/TRPA1. Intraplantar injection of let-7b elicits rapid spontaneous pain via TLR7 and TRPA1. Finally, let-7b can be released from DRG neurons by neuronal activation, and let-7b inhibitor reduces formalin-induced TRPA1 currents and spontaneous pain. Thus, secreted extracellular miRNAs may serve as novel pain mediators via activating TLR7/TRPA1 in nociceptor neurons.

Full Text

Duke Authors

Cited Authors

  • Park, C-K; Xu, Z-Z; Berta, T; Han, Q; Chen, G; Liu, X-J; Ji, R-R

Published Date

  • April 2, 2014

Published In

Volume / Issue

  • 82 / 1

Start / End Page

  • 47 - 54

PubMed ID

  • 24698267

Pubmed Central ID

  • 24698267

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2014.02.011

Language

  • eng

Conference Location

  • United States