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.


OBJECTIVE
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.
Kido
Makiko
M
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka 812-8582, Japan.
Takeuchi
Satoshi
S
Esaki
Hitokazu
H
Hayashida
Sayaka
S
Furue
Masutaka
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004817:Epidermis / Q000294:innervation* / Q000473:pathology*; D005260:Female; D006241:Haptens / Q000737:chemistry; D007249:Inflammation; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016501:Neurites / Q000378:metabolism; D011537:Pruritus / Q000188:drug therapy / Q000473:pathology; D012867:Skin / Q000473:pathology; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology; D014945:Wound Healing
D000893:Anti-Inflammatory Agents; D006241:Haptens; D014498:Uracil; D048369:MAP Kinase Kinase 1; C418807:CX 659S