Recent advances in pruritus research have elucidated mediators and neuronal pathways involved in itch transmission, and this fast emerging knowledge may possibly be translated into new therapies in the near future. In the skin and peripheral nerves, potential mediator and receptor therapeutic targets include the H4 histamine receptor, protease-activated receptor 2, serine proteases, cathepsin S, peripheral mu- and kappa-opioid receptors, interleukin-31, transient receptor potential vanilloid 1 and 3, fatty acid amide hydrolase, nerve growth factor and its receptor, acetylcholine, and the Mas-related G protein-coupled receptors. In the spinal cord, gastrin-related peptide and its receptor, as well as substance P and its receptor neurokinin receptor-1 serve as potential therapeutic targets. In the brain, reduction of itch perception and modulation of emotions may possibly be achieved through drugs acting on the anterior cingulate cortex. Clinically, management of pruritus should be instituted early and should address the skin pathology, peripheral neuropathy, central sensitization, and the cognito-affective aspects of the disease.
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