Evidence for the role of neurogenic inflammation components in trypsin-elicited scratching behaviour in mice
Evidence for the role of neurogenic inflammation components in trypsin-elicited scratching behaviour in mice
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DOI：
10.1038/bjp.2008.172
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发表时间：
2008-07-01
影响因子：
7.3
通讯作者：
Calixto, J. B.
中科院分区：
文献类型：
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作者：
Costa, R.;Marotta, D. M.;Calixto, J. B.
背景和目的：我们研究了胰蛋白酶诱导小鼠瘙痒反应的机制，以评估神经源性炎症成分在这种反应中的相关性。实验方法：通过在小鼠颈部皮内注射胰蛋白酶诱导瘙痒。观察动物40分钟，他们的抓挠behaviorsquantited.Key结果：胰蛋白酶诱导的瘙痒被阻断利马豆胰蛋白酶抑制剂，选择性蛋白酶激活受体-2（PAR-2）拮抗剂FSLLRY和PAR-2受体脱敏。观察到肥大细胞的重要参与，因为用肥大细胞去甲肾上腺素化合物48/80或肥大细胞稳定剂色甘酸二钠长期预处理防止了抓挠。此外，胰蛋白酶反应被选择性考克斯-2抑制剂塞来昔B和选择性激肽B-2（FR 173657）和B-1（SSR 240612）受体拮抗剂抑制。此外，确定了神经源性炎症介质的重要作用，因为选择性NK 1（FK 888）、NK 3（SR 142801）和降钙素基因相关肽（CGRP（8-37）片段）受体拮抗剂抑制胰蛋白酶诱导的瘙痒。类似地，通过选择性TRPV 1受体拮抗剂SB 366791或通过TRPV 1受体的遗传缺失阻断瞬时受体电位香草素1（TRPV 1）受体，减少了小鼠的这种行为。C-纤维脱敏表现出非常相似的结果。结论和影响：胰蛋白酶皮内注射证明是一个可重复的模型瘙痒和PAR-2受体的参与的研究。此外，胰蛋白酶诱导的瘙痒似乎广泛依赖于神经源性炎症，TRPV 1受体发挥作用。此外，位于感觉神经和皮肤中的其他几种介质似乎也有助于这一过程。
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.