Abstract
Itch (or pruritus) is an unpleasant sensation inducing a desire to scratch. As part of the body’s defense mechanism, itch guards the skin against potentially dangerous organisms or stimuli. Moreover, itch is a major and distressing symptom of many skin and systemic diseases. Histamine is the best known pruritogen in humans, and is also regarded as an experimental itch-causing substance. Clinically, antihistamines – that is, H1-receptor blockers – are commonly used for all types of itch resulting from renal and liver diseases, as well as from serious skin diseases, such as atopic dermatitis. However, antihistamines often lack efficacy in patients with chronic itch, as there are many other itch-causing substances, such as proteases, neuropeptides, cytokines and opioids, and their cognate receptors, such as thermoreceptors, PAR-2 and opioid receptors. Recently, potential roles of new histamine receptors in pruritus have also been identified. Itch is transmitted to the CNS by specialized nerve fibers and sensory receptors. Recent studies regarding gastrin-releasing peptide receptors indicated that itch and pain have their own neuronal pathways. As a cutaneous sensory perception, itch may require excitation of neuropeptide-containing free nerve endings of unmyelinated C-fibers, such as gastrin-releasing peptide+ fibers. In addition, neuronal sensitization caused by activation of itch-related receptors on sensory nerve fibers and increases in the number of these fibers, as well as neurogenic inflammation, are partly involved in chronic itch. This review highlights recent knowledge regarding different mechanisms that may be involved in the regulation of itch.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.