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

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

Author information

1
Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institutet, 17177 Stockholm, Sweden.
2
Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden.
3
Alan Edwards Centre for Research on Pain, McGill University, Montréal, Québec H3A 0G1, Canada.
4
Office of Research on Women's Health, National Institutes of Health, Bethesda, MD 20892, USA.
5
Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria.
6
Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institutet, 17177 Stockholm, Sweden. patrik.ernfors@ki.se.

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.

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PMID:
28572455
DOI:
10.1126/science.aam7671
[Indexed for MEDLINE]

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