Itching, Ionic Channels, Immune System, Magnesium and Antioxidants

An itch, or pruritus, is a sensation that induces the need to scratch. Chronic pruritus, which is prevalent in 8-25% of the population, arises from diverse etiologies among which are several skin diseases. Itch originates from a complex interaction between the skin's surface, chemical mediators, and the nervous system, driven by an overactive immune system. A comprehensive review of itching is hereby provided, covering its initial steps, mediators, relationship with the spine, ion channels, topical and systemic treatments, and the effects of magnesium and antioxidants. Ion channels present in keratinocytes, immune cells and sensory neurons play a critical role to preserve skin homeostasis. The dysregulation of ionic channels such as calcium, potassium, sodium, or chloride contributes to the production of inflammation, as well as skin barrier problems, and keratinocyte dysfunction that are key elements in the pathophysiology of itch. There is cross-talk between the three elements that intensify itching. Furthermore, the signals reaching the brain induce scratching, creating a vicious cycle between itching and scratching that further exacerbates itching. In this review, we have examined the important role of ion channels in itch. New medications and clinical trials based on ion channels as therapeutic targets are required to provide tools for the treatment of chronic itch. Magnesium efficiently inhibits itch by modulating voltage- and ligand-gated ion channels. Antioxidants prevent itch by blocking the unwarranted amount of reactive oxygen species (ROS) and dysregulating the innate immune signaling pathways. The strategy combining both magnesium and antioxidants constitutes an important advancement towards new approaches for the treatment of itching with very limited side effects. A number of clinical trials are needed to confirm the usefulness of ion channel-targeted antioxidant and anti-itch strategies to enhance the comprehensiveness and foresight of the conclusions.