Neuron (Cambridge, Mass.), 2014-04, Vol.82 (1), p.47-54
2014
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- Autor(en) / Beteiligte
- Titel
- Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1
- Ist Teil von
- Neuron (Cambridge, Mass.), 2014-04, Vol.82 (1), p.47-54
- Ort / Verlag
- United States: Elsevier Limited
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0896-6273eISSN: 1097-4199DOI: 10.1016/j.neuron.2014.02.011Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3982230
- Format
- –
- Schlagworte
- Animals, Behavior, Disease Models, Animal, Formaldehyde - pharmacology, Ganglia, Spinal - cytology, Gene expression, HEK293 Cells, Humans, Ligands, Membrane Glycoproteins - deficiency, Membrane Glycoproteins - genetics, Membrane Glycoproteins - metabolism, Membrane Potentials - drug effects, Membrane Potentials - physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs, MicroRNAs - adverse effects, MicroRNAs - pharmacology, Myeloid Differentiation Factor 88 - deficiency, Neurons, Nociceptors - drug effects, Pain, Pain - chemically induced, Pain - pathology, Pain Management, Patch-Clamp Techniques, Rodents, Studies, Toll-Like Receptor 7 - deficiency, Toll-Like Receptor 7 - genetics, Toll-Like Receptor 7 - metabolism, Transgenic animals, Transient Receptor Potential Channels - deficiency, Transient Receptor Potential Channels - genetics, Transient Receptor Potential Channels - metabolism, TRPA1 Cation Channel, TRPV Cation Channels - deficiency