Chronic itch: emerging treatments following new research concepts

Abstract

Until recently, itch pathophysiology was poorly understood and treatments were poorly effective in relieving itch. Current progress in our knowledge of the itch processing, the numerous mediators and receptors involved has led to a large variety of possible therapeutic pathways. Currently, inhibitors of IL-31, IL-4/13, NK 1 receptors, opioids and cannabinoids, JAK, PDE4 or TRP are the main compounds involved in clinical trials. However, many new targets, such as Mas-related GPCRs and unexpected new pathways need to be also explored.

Chronic prurigo

“…However, mechanisms are more precisely known and are based on itch sensitization and interactions between pruriceptors and skin cells. 7 In the brain, functional changes associated with sensitization were assessed by an increased activation of many areas associated with structural changes, such as decreased grey matter in some areas. 33 At the spinal cord level, abnormal regulation of inhibitory pathways can explain central sensitization.…”

“…33 At the spinal cord level, abnormal regulation of inhibitory pathways can explain central sensitization. 7 The inhibitory descending pathways are reduced. 34 Dysfunction of Bhlhb5 + interneurons has been shown in mice.…”

“…34 Dysfunction of Bhlhb5 + interneurons has been shown in mice. 35 Peripheral sensitization can be attributed to the increased excitability of sensory neurons due to hyperinnervation or the loss of innervation as well as increased expression, sensitivity and/or responsiveness of pruriceptors, 7,36 which contribute to the hypersensitivity of sensory neurons to pruritogens. 37 In the skin, keratinocytes communicate with sensory nerve endings, especially pruriceptors, via synaptic-like contacts.…”

“…Fortunately, recent research results on the pathophysiology of pruritus allow new therapeutic perspectives. 7 Since the meetings for the discussion of the guidelines, randomized clinical trials on aprepitant, serlopitant and nemolizumab have been published, and other trials are ongoing.…”

“…[1][2][3][4][5][6] Research on itch has been very dynamic for 25 years, and has provided significant advances to start deciphering the molecular and cellular mechanisms underlying itch sensation in the skin and in the peripheral and central nervous systems, allowing hopes for new treatments in the coming years. 7 Although prurigo is not the only clinical manifestation of chronic pruritus, therapeutic trials of antipruritic drugs are focused on chronic prurigo, especially nodular prurigo, because chronic prurigo, as both a cause and consequence of pruritus, is the model of chronic pruritus. This review summarizes the recent discussions on the definition and clinical aspects before approaching epidemiology, pathogenesis and consequences and then identifies therapeutic targets and emerging treatments.…”