Advances in understanding itching and scratching: a new era of targeted treatments

Abstract

Chronic itch is a significant health burden with few effective treatments. As such, itch researchers seek to understand the mechanisms behind itch and to find potential targets for treatment. The field of itch research is dynamic, and many advances have been made so far this decade. In particular, major steps forward include the identification of new peripheral and central itch mediators and modulators, the discovery of greater roles for immune cells and glia in itch transmission, and a focus on the brain processing of itching and scratching. Finally, several new therapeutic interventions for itch have shown success in clinical trials.

Inflammatory mediators causing cutaneous chronic itch in some diseases via transient receptor potential channel subfamily V member 1 and subfamily A member 1

“…There is no standard or general treatment for chronic itch. 3,4,54 Until now, at least 15 small molecular compounds have entered phase 1 clinical trials and five of these antagonists have progressed to phase II clinical trials. Drugs acting on cellular components, including keratinocytes, eosinophils and soluble factors, such as IL-31, IL-4, IL-13 and TSLP, need to be explored.…”

“…A number of TRPV1 antagonists have been developed 53 and some TRPV1 channel inhibitors also trialed at the clinical stage. 3,4,54 Until now, at least 15 small molecular compounds have entered phase 1 clinical trials and five of these antagonists have progressed to phase II clinical trials.…”

“…As such, the relationship between inflammatory mediators and itch must be explored. 3 Many itch-related diseases cause the release of itch mediators which could act on their own receptors expressed in dorsal root ganglion (DRG) neurons. Subsequently, these signals activate the phospholipase C (PLC)/protein kinase C (PKC)/transient receptor potential channel vanilloid 1 (TRPV1)/ transient receptor potential channel ankyrin transmembrane protein 1 (TRPA1) pathway.…”

Commiphora myrrha inhibits itch‑associated histamine and IL‑31 production in stimulated mast cells

“…Therefore, the ultimate aim of AD management is to successfully treat itch. However, treatment is difficult due to a lack of information and an insufficient understanding of itch etiology within AD (2).…”

Non-Histaminergic Itch Mediators Elevated in the Skin of a Porcine Model of Scabies and of Human Scabies Patients

“…Though histamine is considered the classical pruritogen, most types of chronic itch fail to respond to antihistamine treatment. Recent studies have emphasized the importance of nonhistaminergic and neural mechanisms in chronic itch conditions (Sanders et al, 2016). The ion channels TRPV1 and TRPA1 are expressed on itchsignaling primary afferent neurons.…”