Abstract
Cutaneous neurophysiology encompasses specific itch mediators and nerve fibers that transmit itch peripherally and centrally. This chapter provides an overview of fundamental mechanisms of itch, from the skin to the brain. There are two subsets of pruritoceptive C neurons which respond to histamine versus cowhage and then activate distinct spinothalamic tract neurons. Peripheral itch mediators include histamine, proteases, and interleukin-31, while central itch mediators include opioids, gastrin-releasing peptide, and B-type natriuretic peptide. There is an overlap between chronic itch and chronic pain, including activation of multiple brain areas and associated neuromediators and receptors such as nerve growth factor and transient receptor potential (TRP) channels. Therapy with topical and systemic drugs that reduce itch sensitization by counteracting the responsible mediators represent promising treatment strategies.