Peripheral Mechanisms of Itch

A multitude of exogenous environmental stimuli and endogenous molecular and cellular components interface directly or indirectly with the free nerve endings of sensory nerves in the skin. Environmental stimuli include substances derived from the microbiome and materials, such as allergens, that otherwise come in contact with the skin. Endogenous stimuli include components of or mediators derived from the epidermal barrier, keratinocytes, mast cells, and additional resident and skin-homing immune cells. The sensation of itch is ultimately provoked by mediators that interact with and activate pruriceptors on the sensory nerve fibers. These peripheral fibers convey signals from the skin to the dorsal root and trigeminal ganglia and on to the spinal cord and brain where central processing of the itch sensation occurs. A discussion of the nature and sources of itch stimuli and receptors in the periphery form the basis of this chapter. The development of drugs that target these processes is in the process of revolutionizing therapeutic approaches to itch.