Journal Article

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

Harkany, Tibor, Gonzales, Carolina Bengtsson, Häring, Martin, Hjerling-Leffler, Jens, Hökfelt, Tomas, Li, Lili, Belfer, Inna, Abdo, Hind, Parisien, Marc, Peng, Changgeng, Zhang, Ming-Dong, Usoskin, Dmitry, Furlan, Alessandro, Diatchenko, Luda, Ernfors, Patrik, Lallemend, Francois

2017

Overview

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.

• Publisher: American Association for the Advancement of Science
• Subject: Animals / Calcium Channels - genetics / Calcium Channels - metabolism / Gene Expression Regulation - genetics / Mechanoreceptors - physiology / Mice / MicroRNAs - genetics / MicroRNAs - metabolism / Neuralgia - genetics / Nociceptors - physiology / Pain - genetics