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.
Subject(s)
Nociception , Pruritus/metabolism , Receptors, G-Protein-Coupled/metabolism , Sensory Receptor Cells/metabolism , Skin/metabolism , Animals , Mechanotransduction, Cellular , Mice , Mice, Inbred C57BL , Pruritus/physiopathology , Sensory Receptor Cells/cytology , Sensory Receptor Cells/physiology , Skin/physiopathology , Touch PerceptionABSTRACT
Mas-related G protein-coupled receptors (Mrgprs) are a family of receptors implicated in a diverse array of human diseases. Since their discovery in 2001, great progress has been made in determining their relation to human disease. Vital for Mrgprs therapeutic efforts across all disease disciplines is a thorough understanding of Mrgprs signal transduction pathways and polymorphisms, as these offer insights into new drug candidates, existing discrepancies in drug response, and differences in disease susceptibility. In this review, we discuss the current state of knowledge regarding Mrgprs signaling pathways and polymorphisms.
Subject(s)
Polymorphism, Genetic/physiology , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Signal Transduction/physiology , Animals , HumansABSTRACT
Diverse sensory neurons exhibit distinct neuronal morphologies with a variety of axon terminal arborizations subserving their functions. Because of its clinical significance, the molecular and cellular mechanisms of itch are being intensely studied. However, a complete analysis of itch-sensing terminal arborization is missing. Using an MrgprC11CreERT2 transgenic mouse line, we labeled a small subset of itch-sensing neurons that express multiple itch-related molecules including MrgprA3, MrgprC11, histamine receptor H1, IL-31 receptor, 5-hydroxytryptamine receptor 1F, natriuretic precursor peptide B, and neuromedin B. By combining sparse genetic labeling and whole-mount placental alkaline phosphatase histochemistry, we found that itch-sensing skin arbors exhibit free endings with extensive axonal branching in the superficial epidermis and large receptive fields. These results revealed the unique morphological characteristics of itch-sensing neurons and provide intriguing insights into the basic mechanisms of itch transmission.
