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

Abstract

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.

• Authors: Makiko Kido, Satoshi Takeuchi, Hitokazu Esaki, Sayaka Hayashida, Masutaka Furue
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 58 Issue 2 Pg. 130-5 (May 2010) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 20399618 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Haptens
• Uracil
• MAP Kinase Kinase 1
• CX 659S

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Disease Models, Animal
• Epidermis (innervation, pathology)
• Female
• Haptens (chemistry)
• Inflammation
• MAP Kinase Kinase 1 (metabolism)
• Mice
• Mice, Inbred C57BL
• Neurites (metabolism)
• Pruritus (drug therapy, pathology)
• Skin (pathology)
• Uracil (analogs & derivatives, pharmacology)
• Wound Healing