Evidence for the role of neurogenic inflammation components in trypsin-elicited scratching behaviour in mice

被引:76
作者
Costa, R. [1 ]
Marotta, D. M. [1 ]
Manjavachi, M. N. [1 ]
Fernandes, E. S. [1 ,3 ]
Lima-Garcia, J. F. [1 ]
Paszcuk, A. F. [1 ]
Quintao, N. L. M. [1 ]
Juliano, L. [2 ]
Brain, S. D.
Calixto, J. B. [1 ]
机构
[1] Univ Fed Santa Catarina, Dept Pharmacol, Ctr Biol Sci, BR-88049900 Florianopolis, SC, Brazil
[2] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo, Brazil
[3] Kings Coll London, Div Cardiovasc, London WC2R 2LS, England
关键词
trypsin; PAR-2; scratching behaviour; neuropeptides; TRPV1; mast cells;
D O I
10.1038/bjp.2008.172
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background and purpose: We investigated the mechanisms underlying the pruritogenic response induced by trypsin in mice, to assess the relevance of neurogenic inflammation components in this response. Experimental approach: Itching was induced by an intradermal injection of trypsin in the mouse neck. The animals were observed for 40 min and their scratching behaviour was quantified. Key results: Trypsin-induced itching was blocked by the lima bean trypsin inhibitor, the selective proteinase-activated receptor-2 (PAR-2) antagonist FSLLRY and PAR-2 receptor desensitization. An important involvement of mast cells was observed, as chronic pretreatment with the mast cell degranulator compound 48/80 or the mast cell stabilizer disodium cromoglycate prevented scratching. Also, trypsin response was inhibited by the selective COX-2 inhibitor celecoxib and by the selective kinin B-2 (FR173657) and B-1 (SSR240612) receptor antagonists. Moreover, an essential role for the mediators of neurogenic inflammation was established, as the selective NK1(FK888), NK3 (SR142801) and calcitonin gene-related peptide (CGRP(8-37) fragment) receptor antagonists inhibited trypsin-induced itching. Similarly, blockade of transient receptor potential vanilloid 1 (TRPV1) receptors by the selective TRPV1 receptor antagonist SB366791, or by genetic deletion of TRPV1 receptor reduced this behaviour in mice. C-fibre desensitization showed a very similar result. Conclusions and implications: Trypsin intradermal injection proved to be a reproducible model for the study of itching and the involvement of PAR-2 receptors. Also, trypsin-induced itching seems to be widely dependent on neurogenic inflammation, with a role for TRPV1 receptors. In addition, several other mediators located in the sensory nerves and skin also seem to contribute to this process.
引用
收藏
页码:1094 / 1103
页数:10
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