UNDERSTANDING THE ROLE MAS-RELATED G PROTEIN-COUPLED RECEPTORS PLAY IN MEDIATING ITCH SENSATION

Thumbnail Image
Files
STEELE-DISSERTATION-2022.pdf (3.04 MB)
Steele_SupplementaryPermissions.pdf (1.09 MB)
Figure_A9.mov (6.35 MB)
Figure_A8.mov (9.44 MB)
Figure_A7.mov (1.26 MB)
Author(s)
Steele, Haley Rae
Advisor(s)
Editor(s)
Associated Organization(s)
Organizational Unit
Organizational Unit
School of Biological Sciences
School established in 2016 with the merger of the Schools of Applied Physiology and Biology
Series
Series
Collections
Theses and Dissertations
Supplementary to:
Permanent Link
http://hdl.handle.net/1853/66534
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 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.
Sponsor
Date
2022-04-14
Extent
Resource Type
Text
Resource Subtype
Dissertation
Rights Statement
Rights URI