# Deciphering the Piezo2-Merkel cell signaling mechanisms in itch

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $523,883

## Abstract

SUMMARY
Itch is described as an unpleasant sensation that elicits the desire to scratch. Although acute scratching is the
protective mechanism to remove irritants from the skin, chronic itch is debilitating. In addition, chronic itch is
widespread and very difficult to treat because of a lack of understanding of the underlying mechanisms.
Therefore, it is critical to gain a better understanding of the cellular and molecular basis of chronic itch toward
the development of novel and effective therapies. Despite great progress in the past few decades in unraveling
the role of membrane bound G-protein coupled receptors and ion channels, especially transient receptor
potential (TRP) channels in the generation of itch sensation at the levels of primary sensory neurons and spinal
cord, much remains unknown about how the cells and molecules in the skin contribute to the production and
regulation of chronic itch other than the mediation of allergic itch by mast cells.
Pilot studies showed that skin-specific knockout of Piezo2 severely reduced the spontaneous scratching in
multiple mouse models of chronic itch. Moreover, the reduction of spontaneous itch in mice subjected to
experimental dry skin is correlated with a loss of mechanically evoked C-fiber firing mediated by the TRPV1-
positive C-mechanoreceptors. We thus hypothesized that Piezo2-Merkel cell signaling is required for the
generation of spontaneous itch under chronic itch conditions by driving the TRPV1-positive C-
mechanoreceptors under chronic itch conditions. In this grant proposal we will: 1) Use unique genetic
approaches to investigate in vivo functions of the mechanosensitive Piezo2 channels and mechanosensory
Merkel cells in mediating spontaneous itch three well-established mouse models of chronic itch; 2)
Demonstrate that miswiring occurs between the Merkel cells and the pruriceptive C-type mechanoreceptor to
promote spontaneous itch in chronic itch mice, thereby providing the cellular and molecular basis for chronic
itch in multiple mouse models of chronic itch.
Our findings will provide a major contribution to our general understanding of how Piezo2 channels and Merkel
cells affect itch signaling in the skin, and undoubtedly lead to new therapeutic approaches for treating chronic
itch.

## Key facts

- **NIH application ID:** 10454374
- **Project number:** 5R01AR077183-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Hongzhen Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $523,883
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454374

## Citation

> US National Institutes of Health, RePORTER application 10454374, Deciphering the Piezo2-Merkel cell signaling mechanisms in itch (5R01AR077183-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10454374. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*