Abstract
Itch 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 Ca2+-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 Ca2+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.
Original language | English (US) |
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Pages (from-to) | 2172-2184 |
Number of pages | 13 |
Journal | Pain |
Volume | 163 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1 2022 |
Keywords
- Anoctamin 1
- Bilirubin
- Chloroquine
- Itch
- Mrgprs
- Pruriceptors
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Anesthesiology and Pain Medicine