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

Jing Feng, Yonghui Zhao, Zili Xie, Kaikai Zang, Sanja Sviben, Xueming Hu, James A.J. Fitzpatrick, Lu Wen, Yifei Liu, Ting Wang, Katy Lawson, Qin Liu, Yan Yan, Xinzhong Dong, Liang Han, Gregory F. Wu, Brian S. Kim, Hongzhen Hu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article numbereabn4819
JournalScience Translational Medicine
Volume14
Issue number653
DOIs
StatePublished - 13 Jul 2022
Externally publishedYes

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