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Edited by Jeremy Nathans, Johns Hopkins University School of Medicine, Baltimore, MD, and approved March 2, 2021 (received for review November 2, 2020)
Significance
Chronic itch, associated with dermatologic or systemic diseases, is challenging to treat and significantly affects quality of life. In the past several decades, significant progress has been made to help us understand the mechanisms of itch. Due to the ease of application and analysis, all animal itch behavioral assays utilize pruritogens administered to the hairy skin. However, itch occurs to both hairy and hairless glabrous skin. Many medical conditions such as plantar and palmar psoriasis, dyshidrosis, and cholestasis mainly evoke itch in glabrous skin. We here present evidence demonstrating that distinct neuronal populations are responsible for mediating hairy and glabrous skin itch. This study advanced our understanding of itch and will have significant impact on the clinical treatment of itch.
Abstract
Itch arising from glabrous skin (palms and soles) has attracted limited attention within the field due to the lack of methodology. This is despite glabrous itch arising from many medical conditions such as plantar and palmar psoriasis, dyshidrosis, and cholestasis. Therefore, we developed a mouse glabrous skin behavioral assay to investigate the contribution of three previously identified pruriceptive neurons in glabrous skin itch. Our results show that MrgprA3+ and MrgprD+ neurons, although key mediators for hairy skin itch, do not play important roles in glabrous skin itch, demonstrating a mechanistic difference in itch sensation between hairy and glabrous skin. We found that MrgprC11+ neurons are the major mediators for glabrous skin itch. Activation of MrgprC11+ neurons induced glabrous skin itch, while ablation of MrgprC11+ neurons reduced both acute and chronic glabrous skin itch. Our study provides insights into the mechanisms of itch and opens up new avenues for future glabrous skin itch research.
Footnotes
- ↵1To whom correspondence may be addressed. Email: lhan41{at}gatech.edu.
Author contributions: L.H. designed research; H.R.S., Y.X., Y.Z., H.B.H., K.L., Y.N., T.N., and L.H. performed research; H.R.S., Y.X., Y.Z., H.B.H., Y.N., T.N., and L.H. analyzed data; and H.R.S. and L.H. wrote the paper.
The authors declare no competing interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2022874118/-/DCSupplemental.
Data Availability
All study data are included in the article and/or supporting information.
Published under the PNAS license.
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MrgprC11+ sensory neurons mediate glabrous skin itch
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- Neuroscience
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