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Evidence for the role of neurogenic inflammation components in trypsin‐elicited scratching behaviour in mice
Author(s) -
Costa R,
Marotta D M,
Manjavachi M N,
Fernandes E S,
LimaGarcia J F,
Paszcuk A F,
Quintão N L M,
Juliano L,
Brain S D,
Calixto J B
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/bjp.2008.172
Subject(s) - trpv1 , receptor , calcitonin gene related peptide , itching , homologous desensitization , neurogenic inflammation , pharmacology , receptor antagonist , trypsin , chemistry , mast cell , capsaicin , endocrinology , substance p , medicine , antagonist , desensitization (medicine) , immunology , biochemistry , transient receptor potential channel , neuropeptide , enzyme
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 NK 1 (FK888), NK 3 (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. British Journal of Pharmacology (2008) 154 , 1094–1103; doi: 10.1038/bjp.2008.172 ; published online 5 May 2008