PMID- 17336291 OWN - NLM STAT- MEDLINE DCOM- 20070803 LR - 20191210 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 563 IP - 1-3 DP - 2007 Jun 1 TI - Pharmacological characterization of a chronic pruritus model induced by multiple application of 2,4,6-trinitrochlorobenzene in NC mice. PG - 233-9 AB - Female NC/Jic mice were sensitized and challenged repeatedly at 48 h intervals for 10 and 30 days by painting 1% 2,4,6-trinitrochlorobenzene (TNCB) on both ears. Mice challenged with TNCB for 30 days developed an inflammatory dermatitis with high immunoglobulin E (IgE) titer. Histological analysis with acidic Toluidine Blue staining revealed that dermal mast cells markedly differentiated and intensely degranulated, consistent with a dramatic increase in scratching behavior. A significant increase in total scratching events could be observed in mice treated with TNCB for a short period of 10 days. Extending the term of TNCB application to 30 days, the IgE titer and number of mast cells elevated significantly, and thus various drugs were evaluated pharmacologically by using the mice treated with TNCB for 30 days. Terfenadine and cyproheptadine attenuated the chronic scratching behavior. Tacrolimus and dexamethasone were less effective and cromolyn showed no effect. In addition, terfenadine and tacrolimus suppressed the degranulation of mast cells. The present chronic scratching model could be suitable to evaluate drugs effective for suppression of mast cell differentiation and degranulation by irritation, and may represent a promising tool to develop new drugs for inflammatory pruritus associated with, for example, atopic dermatitis. FAU - Yamashita, Hirotaka AU - Yamashita H AD - Graduate School of Phrmaceutical Science, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. FAU - Makino, Toshiaki AU - Makino T FAU - Mizukami, Hajime AU - Mizukami H FAU - Nose, Mitsuhiko AU - Nose M LA - eng PT - Evaluation Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070208 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Antipruritics) RN - 2YHB6175DO (Cyproheptadine) RN - 37341-29-0 (Immunoglobulin E) RN - 7BA5G9Y06Q (Terfenadine) RN - 7S5I7G3JQL (Dexamethasone) RN - Q2WXR1I0PK (Cromolyn Sodium) RN - WM0HAQ4WNM (Tacrolimus) RN - Z4ZG7O5SZ9 (Picryl Chloride) SB - IM MH - Animals MH - Antipruritics/*pharmacology/therapeutic use MH - Cell Degranulation/drug effects MH - Chronic Disease MH - Cromolyn Sodium/pharmacology MH - Cyproheptadine/pharmacology MH - Dermatitis, Atopic/chemically induced/*complications/drug therapy/immunology/physiopathology MH - Dexamethasone/pharmacology MH - *Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Drug Evaluation, Preclinical/*methods MH - Female MH - Immunoglobulin E/blood MH - Mast Cells/drug effects/immunology MH - Mice MH - *Picryl Chloride MH - Pruritus/etiology/immunology/physiopathology/*prevention & control MH - Tacrolimus/pharmacology MH - Terfenadine/pharmacology MH - Time Factors EDAT- 2007/03/06 09:00 MHDA- 2007/08/04 09:00 CRDT- 2007/03/06 09:00 PHST- 2006/09/13 00:00 [received] PHST- 2007/01/22 00:00 [revised] PHST- 2007/01/25 00:00 [accepted] PHST- 2007/03/06 09:00 [pubmed] PHST- 2007/08/04 09:00 [medline] PHST- 2007/03/06 09:00 [entrez] AID - S0014-2999(07)00142-2 [pii] AID - 10.1016/j.ejphar.2007.01.078 [doi] PST - ppublish SO - Eur J Pharmacol. 2007 Jun 1;563(1-3):233-9. doi: 10.1016/j.ejphar.2007.01.078. Epub 2007 Feb 8.