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bioRxiv · 10.1101/2022.06.22.497257

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

Lu, P.·Zhao, Y.·Xie, Z.·Dong, X.·Wu, G.·Kim, B.·Feng, J.·Hu, H.
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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 through activation of the PLC-PKC{delta} signaling. Collectively, our data uncovered a TRPV1+/MrgprA3+ prurioceptor-Piezo2 signaling axis in the initiation of pruritogen-induced mechanical itch sensitization in the skin.

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Lu, P., Zhao, Y., Xie, Z., Dong, X., Wu, G., Kim, B., Feng, J., Hu, H.. 2022-06-26. MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel. https://doi.org/10.1101/2022.06.22.497257

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