The insulin receptor regulates the persistence of mechanical nociceptive sensitization in flies and mice.
The insulin receptor regulates the persistence of mechanical nociceptive sensitization in flies and mice.
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早期糖尿病通常伴有疼痛敏感性。在果蝇中，胰岛素受体（InR）调节损伤诱导的热伤害性敏化的持续性。果蝇InR是否也调节机械伤害性敏化的持续性仍不清楚。感觉神经元缺失胰岛素受体（Insr）的小鼠表现出正常的伤害性基线，然而，它是不确定的是否缺失Insr的伤害性感觉神经元导致持续的伤害性超敏反应。在这项研究中，我们使用苍蝇和小鼠伤害性致敏模型来解决这些问题。在果蝇中，InR突变体和幼虫的感觉神经元特异性表达的RNAi转基因靶向InR表现出持续的机械超敏反应。在Nav1.8+伤害性感觉神经元中具有Insr基因特异性缺失的小鼠显示出与对照相似的伤害性热和机械基线。然而，在炎症范例中，这些突变小鼠表现出持续的机械（但不是热）超敏反应，特别是在雌性小鼠中。具有Nav1.8+感觉神经元特异性Insr缺失的小鼠没有显示出典型的全身胰岛素信号传导缺陷的代谢异常。我们的研究结果表明，某些方面的调节伤害性超敏反应的胰岛素受体之间共享苍蝇和小鼠，这种调节可能是独立的代谢效应。总结：本文证明了胰岛素受体在调节果蝇和小鼠损伤诱导的机械伤害感受的持续性中的保守作用。
Early phase diabetes is often accompanied by pain sensitization. In Drosophila, the insulin receptor (InR) regulates the persistence of injury-induced thermal nociceptive sensitization. Whether Drosophila InR also regulates the persistence of mechanical nociceptive sensitization remains unclear. Mice with a sensory neuron deletion of the insulin receptor (Insr) show normal nociceptive baselines; however, it is uncertain whether deletion of Insr in nociceptive sensory neurons leads to persistent nociceptive hypersensitivity. In this study, we used fly and mouse nociceptive sensitization models to address these questions. In flies, InR mutants and larvae with sensory neuron-specific expression of RNAi transgenes targeting InR exhibited persistent mechanical hypersensitivity. Mice with a specific deletion of the Insr gene in Nav1.8+ nociceptive sensory neurons showed nociceptive thermal and mechanical baselines similar to controls. In an inflammatory paradigm, however, these mutant mice showed persistent mechanical (but not thermal) hypersensitivity, particularly in female mice. Mice with the Nav1.8+ sensory neuron-specific deletion of Insr did not show metabolic abnormalities typical of a defect in systemic insulin signaling. Our results show that some aspects of the regulation of nociceptive hypersensitivity by the insulin receptor are shared between flies and mice and that this regulation is likely independent of metabolic effects. Summary: This paper demonstrates a conserved role for the insulin receptor in regulating the persistence of injury-induced mechanical nociception in flies and mice.
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影响因子：
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作者：
Dabbara H;Schultz A;Im SH
通讯作者：
Im SH
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影响因子：
3.3
作者：
Liu S;Lv Y;Wan XX;Song ZJ;Liu YP;Miao S;Wang GL;Liu GJ
通讯作者：
Liu GJ
影响因子：
5.3
作者：
Grote CW;Wilson NM;Katz NK;Guilford BL;Ryals JM;Novikova L;Stehno-Bittel L;Wright DE
通讯作者：
Wright DE
DOI：
10.3791/61911
发表时间：
2020-10-29
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Lopez-Bellido R;Galko MJ
通讯作者：
Galko MJ