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在 GTN 偏头痛小鼠模型中寻找非诱发性疼痛标志物。

The search for non-evoked markers of pain in the GTN mouse model of migraine.

机构信息

Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.

Translational Research Centre, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.

出版信息

Sci Rep. 2024 Nov 3;14(1):26481. doi: 10.1038/s41598-024-78332-3.

DOI:10.1038/s41598-024-78332-3
PMID:39489838
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11532339/
Abstract

Rodent migraine models have been developed to study the underlying molecular mechanisms of migraine, but these need further development and validation to stay relevant. The glyceryl trinitrate (GTN) mouse model with tactile hypersensitivity as the primary readout, has been highly used to understand the pathophysiology of migraine. Nevertheless, this readout has questionable translatability to the experience of spontaneous pain and additional readouts are needed to improve this model. We explored the applicability of several spontaneous behaviours and burrowing activity as additional markers to detect effects of repeated GTN injections in mice. We used the Laboratory Animal Behaviour Observation Registration and Analysis System (LABORAS) test system to understand the potential effect of GTN on locomotion and other behavioral parameters in two different experiments. Burrowing was used to investigate the potential effect on GTN on a voluntary innate behavior of mice. We found no clear effect of GTN on either locomotion or burrowing in these experiments. With our experimental design, there was no significant difference between GTN and vehicle and neither locomotion nor burrowing activity will readily supplement the von Frey test. The search for additional none-evoked markers of pain in rodent migraine models will continue.

摘要

啮齿动物偏头痛模型已被开发用于研究偏头痛的潜在分子机制,但这些模型需要进一步开发和验证才能保持相关性。以触觉过敏为主要指标的甘油三硝酸酯(GTN)小鼠模型已被广泛用于理解偏头痛的病理生理学。然而,这种指标对于自发性疼痛的体验具有可疑的可转化性,需要额外的指标来改进该模型。我们探讨了几种自发性行为和挖掘活动作为额外指标的适用性,以检测重复 GTN 注射对小鼠的影响。我们使用实验室动物行为观察登记和分析系统(LABORAS)测试系统,在两个不同的实验中了解 GTN 对运动和其他行为参数的潜在影响。挖掘被用来研究 GTN 对小鼠自愿先天行为的潜在影响。我们在这些实验中没有发现 GTN 对运动或挖掘有明显的影响。根据我们的实验设计,GTN 和载体之间没有显著差异,运动和挖掘活动都不会轻易补充冯·弗雷测试。在啮齿动物偏头痛模型中寻找额外的非诱发疼痛标志物的研究将继续进行。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2604/11532339/ce9f8d5b7b9b/41598_2024_78332_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2604/11532339/a14b9fb76b3a/41598_2024_78332_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2604/11532339/666ce03e931b/41598_2024_78332_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2604/11532339/d63b3ed3cd5b/41598_2024_78332_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2604/11532339/ce9f8d5b7b9b/41598_2024_78332_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2604/11532339/a14b9fb76b3a/41598_2024_78332_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2604/11532339/666ce03e931b/41598_2024_78332_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2604/11532339/d63b3ed3cd5b/41598_2024_78332_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2604/11532339/ce9f8d5b7b9b/41598_2024_78332_Fig4_HTML.jpg

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本文引用的文献

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Physiol Behav. 2022 Nov 1;256:113956. doi: 10.1016/j.physbeh.2022.113956. Epub 2022 Aug 31.
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Smooth muscle ATP-sensitive potassium channels mediate migraine-relevant hypersensitivity in mouse models.平滑肌 ATP 敏感性钾通道介导小鼠模型中的偏头痛相关过敏反应。
Cephalalgia. 2022 Feb;42(2):93-107. doi: 10.1177/03331024211053570. Epub 2021 Nov 24.
3
CGRP-dependent signalling pathways involved in mouse models of GTN- cilostazol- and levcromakalim-induced migraine.
涉及 GTN-西洛他唑-和利马前列素诱导偏头痛的小鼠模型中 CGRP 依赖性信号通路。
Cephalalgia. 2021 Dec;41(14):1413-1426. doi: 10.1177/03331024211038884. Epub 2021 Aug 18.
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Nitric oxide role in anxiety-like behavior, memory and cognitive impairments in animal model of chronic migraine.一氧化氮在慢性偏头痛动物模型的焦虑样行为、记忆及认知障碍中的作用
Heliyon. 2020 Dec 7;6(12):e05654. doi: 10.1016/j.heliyon.2020.e05654. eCollection 2020 Dec.
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No additive effect of combining sumatriptan and olcegepant in the GTN mouse model of migraine.在偏头痛的 GTN 小鼠模型中,舒马曲坦和欧立吉林联合使用没有相加作用。
Cephalalgia. 2021 Mar;41(3):329-339. doi: 10.1177/0333102420963857. Epub 2020 Oct 15.
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ATP sensitive potassium (K) channel inhibition: A promising new drug target for migraine.三磷酸腺苷敏感性钾(K)通道抑制:偏头痛有希望的新药物靶点。
Cephalalgia. 2020 Jun;40(7):650-664. doi: 10.1177/0333102420925513. Epub 2020 May 16.
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