Neurobiology of Itch (Pruritus)

Abstract Itch is often defined as an ‘unpleasant sensation that provokes the desire to scratch’. Recent studies have provided novel insights into the molecular mechanisms underlying itch‐selective signalling pathways from the periphery to the central nervous system. Chronic itch is often associated with inflammatory skin diseases such as atopic dermatitis, psoriasis or contact dermatitis, as well as systemic diseases such as renal, cholestatic, hematologic or endocrine pruritus or pruritus related to malignancy, and reduces quality of life. Chronic itch is thought to involve the sensitisation of itch‐signalling pathways, the molecular and cellular processes of which we are just starting to uncover. This review article describes recent findings regarding the basic mechanisms of itch transmission from the skin to the brain. We further describe the neuronal changes that occur both peripherally and centrally under conditions of chronic itch. Key Concepts There are a variety of endogenous pruritogens and external itch stimuli. Itch transducing channels include TRPV1, TRPA1 and Nav1.7. Spinal excitatory and inhibitory interneurons process itch information. Descending noradrenergic and serotonergic systems modulate spinal itch transmission. Sensitisation occurs in both peripheral and central nervous system under conditions of chronic itch. NK1‐expressing spinal neurons play a major role in itch sensitisation.