Papers of the Week

Pruritus (or itch) is an unpleasant sensation leading to a desire to scratch. In the epidermis, are selective C or Aδ epidermal nerve endings which are pruriceptors. At their other ends, peripheral neurons form synapses with spinal neurons and interneurons. Many areas in the central nervous system are involved in itch processing. Although itch does not occur solely because of parasitic, allergic, or immunological diseases, it is usually the consequence of neuro-immune interactions. Histamine is involved in a minority of itchy conditions, and many other mediators play a role: cytokines (e.g., IL-4, IL-13, IL-31, IL-33, and TSLP), neurotransmitters (e.g., substance P, CGRP, VIP, neuropeptide Y, NBNP, endothelin 1, and GRP), and neurotrophins (e.g., NGF and BDNF). Moreover, ion channels such as NaVs, TRPV1, TRPA1, and TRPM8 play a crucial role. The main markers of nonhistaminergic pruriceptors are PAR-2 and MrgprX2. A notable phenomenon is the sensitization to pruritus, in which, regardless of the initial cause of pruritus, there is an increased responsiveness of peripheral and central pruriceptive neurons to their normal or subthreshold afferent input, in the context of chronic itch.