The role of the Mrgpr receptor family in itch

Itch is a complex sensory modality that can be evoked by an extremely diverse set of stimuli and has multiple components of disease etiology. Thus, determining the basic molecular and cellular players is essential before we can tackle the more complex aspects of itch. The identification of novel itch receptors has been extremely fruitful and has uncovered novel signaling pathways and pruritogens. Mrgprs encode a family of G protein-coupled receptors, many of which are expressed specifically in sensory nerves and function as itch receptors in mediating histamine-independent itch. In this chapter, we will review the discovery of the receptor family, their specific expression, their roles as itch receptors, and the itch-inducing agonists. Furthermore, we will summarize the results indicating that Mrgpr-expressing sensory neurons are itch-sensing neurons. In the end we will discuss the role of Mrgprs and Mrgpr-positive neurons in chronic itch.