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Papers of the Week


Papers: 16 Jul 2022 - 22 Jul 2022


2022 Jul 13


Sci Transl Med


14


653

Editor's Pick

Miswiring of Merkel cell and pruriceptive C fiber drives the itch-scratch cycle.

Authors

Feng J, Zhao Y, Xie Z, Zang K, Sviben S, Hu X, Fitzpatrick JAJ, Wen L, Liu Y, Wang T, Lawson K, Liu Q, Yan Y, Dong X, Han L, Wu GF, Kim BS, Hu H
Sci Transl Med. 2022 Jul 13; 14(653):eabn4819.
PMID: 35857641.

Abstract

Itch sensation provokes the scratch reflex to protect us from harmful stimuli in the skin. Although scratching transiently relieves acute itch through activation of mechanoreceptors, it propagates the vicious itch-scratch cycle in chronic itch by further aggravating itch over time. Although well recognized clinically, the peripheral mechanisms underlying the itch-scratch cycle remain poorly understood. Here, we show that mechanical stimulation of the skin results in activation of the Piezo2 channels on Merkel cells that pathologically promotes spontaneous itch in experimental dry skin. Three-dimensional reconstruction and immunoelectron microscopy revealed structural alteration of MRGPRA3 pruriceptor nerve endings directed toward Merkel cells in the setting of dry skin. Our results uncover a functional miswiring mechanism under pathologic conditions, resulting in touch receptors triggering the firing of pruriceptors in the skin to drive the itch-scratch cycle.