Endothelin-1 induces itch and pain in the mouse cheek model
Endothelin-1 induces itch and pain in the mouse cheek model
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DOI：
10.1016/j.lfs.2012.03.020
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发表时间：
2012-10-15
期刊：
影响因子：
6.1
通讯作者：
Rae, Giles Alexander
中科院分区：
文献类型：
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作者：
Gomes, Lenyta Oliveira;Hara, Daniela Balz;Rae, Giles Alexander
目的：迄今为止，内皮素 -1（ET -1）导致痛觉和瘙痒的观点是基于临床前模型的结果，在这些模型中，对瘙痒和痛觉刺激的反应无法区分。本研究在新的小鼠脸颊模型中重新检验了ET -1的这些感觉效应，在该模型中，致痒原和致痛原会引发不同的行为反应。
主要方法：小鼠在左侧脸颊皮内注射测试物质，指向注射部位的后肢搔抓发作或前爪擦拭分别被视为瘙痒和痛觉的指征。
关键发现：组胺和辣椒素分别选择性地引发搔抓和擦拭，而ET -1（3 - 60皮摩尔）促进了两种行为的剂量依赖性发作。虽然BQ -788（一种ETB受体拮抗剂）增强了对ET -1（30皮摩尔）的搔抓和擦拭反应，并且BQ -788与BQ -123（一种ETA受体拮抗剂）共同注射会降低这些反应，但单独使用BQ -123仅抑制搔抓反应。CTOP（μ - 阿片受体选择性拮抗剂）仅增强了对ET -1的搔抓反应，而DAMGO（μ - 阿片受体选择性激动剂）减少了两种行为。氯雷他定（组胺H -1受体拮抗剂）略微减少搔抓，但显著抑制擦拭。
意义：这些结果表明，ET -1在小鼠脸颊模型中引发瘙痒和痛觉行为。对ET -1的两种反应似乎都通过ETA受体介导，并受到同时的ETB受体激活的限制。作用于μ - 阿片受体的局部内源性阿片类物质选择性地调节对ET -1的瘙痒反应，而可能来自肥大细胞并作用于H1受体的组胺在该模型中对ET -1的痛觉效应有重要贡献。（c）2012爱思唯尔公司。保留所有权利。
Aims: To date, suggestions that endothelin-1 (ET-1) causes nociception and pruritus are based on results in preclinical models in which responses to pruritic and nociceptive stimuli cannot be distinguished. This study reexamines these sensory effects of ET-1 in the new mouse cheek model, in which pruritogens and algogens evoke distinct behavioral responses.Main methods: Mice received intradermal (i.d.) injections of test substances into the left cheek and bouts of hind limb scratches or forepaw wipes, directed to the injection site, were considered indicative of pruritus and nociception, respectively.Key findings: Histamine and capsaicin selectively evoked scratching and wipes, respectively, whereas ET-1 (3-60 pmol) promoted dose-dependent bouts of both behaviors. While scratching and wipe responses to ET-1 (30 pmol) were potentiated by BQ-788 (an ETB receptor antagonist) and reduced by co-injection of BQ-788 plus BQ-123 (an ETA receptor antagonist), BQ-123 alone inhibited scratching responses only. CTOP (mu-opioid receptor selective antagonist) only augmented scratching responses to ET-1, whereas DAMGO (mu-opioid receptor selective agonist) reduced both behaviors. Loratadine (histamine H-1 receptor antagonist) marginally reduced scratching, but markedly suppressed wipes.Significance: These results demonstrate that ET-1 evokes pruritic and nociceptive behaviors in the mouse cheek model. Both responses to ET-1 appear to be mediated via ETA receptors and subjected to limitation by simultaneous ETB receptor activation. Local endogenous opioids acting on g-opioid receptors selectively modulate the pruritic response to ET-1, whereas histamine, possibly derived from mast cells and acting on HI receptors, contributes importantly to the nociceptive effect of ET-1 in this model. (c) 2012 Elsevier Inc. All rights reserved.