Scratching behavior does not necessarily correlate with epidermal nerve fiber sprouting or inflammatory cell infiltration

Background: Increased sprouting of epidermal nerve fibers of lesional skin are thought to be associated with persistent pruritus in chronic inflammatory dermatitis such as atopic dermatitis as supported by a murine study using tacrolimus (or FK506: FK) which was shown to inhibit both epidermal sprouting of nerves and scratching behavior or by immunohistochemical observations of lesional skin in the patients with atopic dermatitis or prurigo, etc. Objectives: To examine a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 (MEK1/2) inhibitor (CX-659S: CX) for a possible anti-pruritic property in vivo since some MEK1/2 inhibitors have been reported to inhibit neurite growth in vitro. Methods: CX, FK and corticosteroids (betamethasone valerate: BV) were topically applied on inflamed skin in a mouse model of chronic dermatitis using repetitive hapten painting to examine anti-pruritic property and anti-inflammatory effects. Scratching behaviors were assessed using MicroAct automatic measuring system, and epidermal sprouting of nerves and skin inflammation was assessed histologically. Results: FK significantly decrease scratching behavior, but CX and BV failed to do so despite of their ability to significantly inhibit epidermal nerve fiber sprouting and skin inflammation, respectively. In addition, CX. +. BV mixture synergistically inhibited epidermal nerve fiber sprouting and skin inflammation even more potently than FK without decreasing scratching behavior. Conclusions: These findings suggest that the scratching behavior does not necessarily correlate with epidermal nerve fiber sprouting or inflammatory cell infiltration.