miR-183 cluster scales mechanical pain sensitivity by regulating basal and neuropathic pain genes.
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.
Peng, C; Li, L; Zhang, M-D; Bengtsson Gonzales, C; Parisien, M; Belfer, I; Usoskin, D; Abdo, H; Furlan, A; Häring, M; Lallemend, F; Harkany, T; Diatchenko, L; Hökfelt, T; Hjerling-Leffler, J; Ernfors, P
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