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

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Science  01 Jun 2017:
eaam7671
DOI: 10.1126/science.aam7671

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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 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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