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Papers of the Week


Papers: 25 Mar 2023 - 31 Mar 2023

RESEARCH TYPE:
Basic Science


Animal Studies, Molecular/Cellular, Neurobiology

PAIN TYPE:
Itch


2023 Mar 22


Cell Rep


36961815


42


4

MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel.

Authors

Lu P, Zhao Y, Xie Z, Zhou H, Dong X, Wu GF, Kim BS, Feng J, Hu H

Abstract

Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sensitization are poorly understood. Here, we show that intradermal injections of histamine or chloroquine (CQ) provoke alloknesis through activation of TRPV1- and MrgprA3-expressing prurioceptors, and functional ablation of these neurons reverses pruritogen-induced alloknesis. Moreover, genetic ablation of mechanosensitive Piezo2 channel function from MrgprA3-expressing prurioceptors also dampens pruritogen-induced alloknesis. Mechanistically, histamine and CQ sensitize Piezo2 channel function, at least in part, through activation of the phospholipase C (PLC) and protein kinase C-δ (PKCδ) signaling. Collectively, our data find a TRPV1/MrgprA3 prurioceptor-Piezo2 signaling axis in the initiation of pruritogen-induced mechanical itch sensitization in the skin.