Role of mast cells and basophils in pruritus

To protect our body systems, there is a constant interactive conversation between the skin nervous and immune system. Important elements of this conversation in the skin include mast cells, basophils, and sensory nerve fibers. These cells employ a vast array of sensors that detect danger and react accordingly. This reaction, summarized as neurogenic inflammation, manifests at the conscious level as sensations including pain and itch. Here we provide a perspective on the blossoming knowledge that is illuminating connections between mast cells, basophils, and sensory nerve fibers in the mediation of itch. We discuss established mediators and receptors, in particular cytokine and neuropeptide pathways, upstream proteases, and proteinase-activated receptors, and the emerging role of mas-related G-protein-coupled receptors in itch.