Understanding the switch from pain-to-itch in dermatitis.

evere chronic itch is debilitating symptom that results from a large umber of pathological conditions including skin disorders, organ ailure, and even some types of cancers [1]. In particular, conditions hat are associated with inflammation of the skin—such as atopic ermatitis and contact dermatitis—commonly result in itch that is ifficult to treat. Moreover, excessive scratching causes skin damge and release of inflammatory mediators that exacerbates itch, esulting in a pathological itch-scratch cycle. However, currently here are no effective drugs for the treatment of itch in dermatiis. While antihistamines reduce itch caused by hives, they have imited efficacy for most other types of itch, including atopic and ontact dermatitis. Recently, there has been a surge of interest in the field of itch, nd a large number of new pruritogens (itch-inducing agents) and heir receptors have been identified. Of these, histamine is the prootypical pruritogen, which is released from dermal mast cells and ctivates mechano-insensitive C-fibers to produce itch [2]. In addiion to histamine, there are numerous other pruritogens such as owhage, chloroquine, bovine adrenal medulla 8-22 (BAM8-22), nd serotonin, that likely cause itch via the activation of a disinct population (or populations) of primary afferents [3–8]. These gents cause acute itch in humans and/or trigger vigorous scratchng behavior when injected into the skin of mice. However, we still o not understand which factors are responsible for itch in disease tates like dermatitis, highlighting the pressing need for a better nderstanding of mechanisms underlying chronic itch. Just as people who suffer from chronic pain often experince hyperalgesia and allodynia, people suffering from chronic tch often experience hyperknesis and alloknesis. This ‘itchy-skin’ s commonly seen in dermatitis, where numerous innocuus stimuli—light touch, gentle brushing or contact with wool ber—cause extraneous itch [9,10]. Moreover, substances such as radykinin, which are normally experienced as painful, inappropritely cause itch rather than pain for people with atopic dermatitis 11].