Doctor of Philosophy in Biology

In the

School of Biological Sciences

Haley Rae Steele

Will defend her dissertation

Understanding The Role Mas-Related G Protein-Coupled Receptors Play

In Mediating Itch Sensation

5, April, 2022

2:00 PM

EBB CHOA Seminar Room or BlueJeans Link: https://bluejeans.com/573349989/1538

 Thesis Advisor:

Liang Han, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Committee Members:

Todd Streelman, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Tim Cope, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Yuhong Fan, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Mark Wheeler, Ph.D.

School of Psychology

Georgia Institute of Technology

ABSTRACT: Although chronic itch is the most common reason for visiting the dermatologist, there remain few effective treatments. Glabrous skin itch, which occurs on the palms of hands and soles of feet, is extremely debilitating. However, despite arising from a variety of medical conditions (plantar and palmar psoriasis, dyshidrosis, and cholestasis), it has attracted little attention within the field due to a lack of methodology. Therefore, to identify the neuronal populations mediating glabrous skin itch we examined the central and peripheral innervation pattern of three previously identified itch-sensing neurons (MrgprA3⁺, MrgprD⁺, and MrgprC11⁺). We found that both MrgprD⁺ and MrgprC11⁺ sensory neurons densely innervate glabrous skin, while MrgprA3⁺ sensory neurons do so only very sparsely. These results indicate, for the first time, the potential mechanistic differences that exist between hairy and glabrous skin itch. To investigate and the mechanisms of glabrous skin itch, we developed novel acute and chronic mouse behavioral assays to examine itch sensation arising from the glabrous skin of the plantar hindpaw. We found that mice exhibit specific biting behavior in response to itch-agonists and licking in response to pain-agonists.  Using this assay, we then demonstrated that specific-activation of MrgprA3⁺ and MrgprD⁺ nerves in the glabrous skin do not induce biting behavior, suggesting that they do not mediate glabrous skin itch. In contrast, we found that activation of MrgprC11⁺ neurons induced significant dose-dependent biting (itch) behaviors in glabrous skin. Finally, we found that ablation of MrgprC11⁺ neurons almost completely abolishes both acute and chronic glabrous skin itch. These results suggest that MrgprC11⁺ neurons are a major mediator of glabrous skin itch. In summary, our findings reveal new avenues for future glabrous skin itch study and the development of glabrous-skin specific anti-itch therapies.