title: A novel animal model of pruritus induced by successive application of glucocorticoid to mouse skin.
abstract: Topical glucocorticoids are commonly applied for treatment of atopic dermatitis, and are often administered over a long period. However, itching often occurs as a rebound phenomenon after cessation of long-term glucocorticoid application. The present study was an initial trial designed to establish an animal model of glucocorticoid-induced pruritus by topical application of dexamethasone over a long period in mice with contact dermatitis. BALB/c mice with chronic allergic contact dermatitis induced by 5 weeks of repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) were treated topically with dexamethasone for 3 weeks from 2 weeks after the elicitation of dermatitis. The effects of dexamethasone on inflammation and pruritus were evaluated by measurement of ear-swelling and scratching behavior, respectively. Significant enhancement of pruritus was confirmed after chronic application of dexamethasone. The increased frequency of scratching behavior was reduced by withdrawal of dexamethasone. On the other hand, ear-swelling was markedly ameliorated by dexamethasone treatment, but rapidly relapsed after dexamethasone withdrawal. The level of interleukin (IL)-4 mRNA in ear skin and that of IgE in serum were increased in the mice with dermatitis and reduced by dexamethasone treatment. On the other hand, the level of nerve growth factor (NGF) mRNA was slightly increased by dexamethasone treatment and remained high even after its discontinuation. It is anticipated that this novel animal model of glucocorticoid-induced pruritus will be useful for clarifying the mechanisms of the rebound phenomenon induced by chronic treatment with topical glucocorticoids, and for developing a new form of therapy.
authors.affiliation: Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Japan. yamaura@p.chiba-u.ac.jp
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yamaura
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Doi
authors.forename: Eriko
authors.initials: E
authors.lastname: Suwa
authors.forename: Koichi
authors.initials: K
authors.lastname: Ueno
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010853:Picryl Chloride / Q000494:pharmacology; D011537:Pruritus / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D012333:RNA, Messenger; D007073:Immunoglobulin E; D003907:Dexamethasone; D010853:Picryl Chloride