• Hyesu Kim, Hyungsup Kim, Hawon Cho, Byeongjun Lee, Huan-Jun Lu, Kyungmin Kim, Sooyoung Chung, Won-Sik Shim, Young Kee Shin, Xinzhong Dong, John N Wood, and Uhtaek Oh.
• Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea.
• Pain. 2022 Nov 1; 163 (11): 2172-2184.

AbstractItch is an unpleasant sensation that evokes a desire to scratch. Pathologic conditions such as allergy or atopic dermatitis produce severe itching sensation. Mas-related G protein receptors (Mrgprs) are receptors for many endogenous pruritogens. However, signaling pathways downstream to these receptors in dorsal root ganglion (DRG) neurons are not yet understood. We found that anoctamin 1 (ANO1), a Ca 2+ -activated chloride channel, is a transduction channel mediating Mrgpr-dependent itch signals. Genetic ablation of Ano1 in DRG neurons displayed a significant reduction in scratching behaviors in response to acute and chronic Mrgpr-dependent itch models and the epidermal hyperplasia induced by dry skin. In vivo Ca 2+ imaging and electrophysiological recording revealed that chloroquine and other agonists of Mrgprs excited DRG neurons via ANO1. More importantly, the overexpression of Ano1 in DRG neurons of Ano1 -deficient mice rescued the impaired itching observed in Ano1 -deficient mice. These results demonstrate that ANO1 mediates the Mrgpr-dependent itch signaling in pruriceptors and provides clues to treating pathologic itch syndromes.Copyright © 2022 International Association for the Study of Pain.

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