Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Semmelweis u. 6, Szeged, H-6725, Hungary.
MTA-SZTE Neuroscience Research Group, Szeged, Hungary.
J Headache Pain. 2020 Aug 15;21(1):101. doi: 10.1186/s10194-020-01169-4.
Although migraine is one of the most common primary headaches, its therapy is still limited in many cases. The use of animal models is crucial in the development of novel therapeutic strategies, but unfortunately, none of them show all aspects of the disease, therefore, there is a constant need for further improvement in this field. The application of inflammatory agents on the dura mater is a widely accepted method to mimic neurogenic inflammation in rodents, which plays a key role in the pathomechanism of migraine. Complete Freund's Adjuvant (CFA), and a mixture of inflammatory mediators, called inflammatory soup (IS) are often used for this purpose.
To examine the activation pattern that is caused by chemical stimulation of dura mater, we applied CFA or IS over the right parietal lobe. After 2 h and 4 h (CFA groups), or 2.5 h and 4 h (IS groups), animals were perfused, and c-Fos immunoreactive cells were counted in the caudal trigeminal nucleus. To explore every pitfall, we examined whether our surgical procedure (anesthetic drug, stereotaxic apparatus, local lidocaine) can alter the results under the same experimental settings. c-Fos labeled cells were counted in the second-order neuron area based on the somatotopic organization of the trigeminal nerve branches.
We could not find any difference between the CFA and physiological saline group neither 2 h, nor 4 h after dural stimulation. IS caused significant difference after both time points between IS treated and control group, and between treated (right) and control (left) side. Stereotaxic frame usage had a substantial effect on the obtained results.
Counting c-Fos immunoreactive cells based on somatotopic organization of the trigeminal nerve helped to examine the effect of chemical stimulation of dura in a more specific way. As a result, the use of IS over the parietal lobe caused activation in the area of the ophthalmic nerve. To see this effect, the use of lidocaine anesthesia is indispensable. In conclusion, application of IS on the dura mater induces short-term, more robust c-Fos activation than CFA, therefore it might offer a better approach to model acute migraine headache in rodents.
尽管偏头痛是最常见的原发性头痛之一，但在许多情况下，其治疗仍然有限。动物模型在开发新的治疗策略中至关重要，但不幸的是，没有一种模型能够表现出疾病的所有方面，因此，该领域需要不断改进。在硬脑膜上应用炎症剂是模拟啮齿动物神经源性炎症的一种广泛接受的方法，这种炎症在偏头痛的发病机制中起着关键作用。完全弗氏佐剂（CFA）和一种称为炎症汤（IS）的炎症介质混合物常用于此目的。
为了研究化学刺激硬脑膜引起的激活模式，我们在右顶叶上应用 CFA 或 IS。在 CFA 组 2 小时和 4 小时后，或 IS 组 2.5 小时和 4 小时后，动物被灌注，在尾状核中计算 c-Fos 免疫反应性细胞的数量。为了探索每一个陷阱，我们检查了在相同的实验设置下，我们的手术程序（麻醉药物、立体定向仪器、局部利多卡因）是否会改变结果。根据三叉神经分支的躯体定位组织，在二级神经元区域计数 c-Fos 标记细胞。
我们在硬脑膜刺激后 2 小时和 4 小时都没有发现 CFA 组和生理盐水组之间的任何差异。IS 在两个时间点都引起了 IS 处理组与对照组之间以及处理（右侧）和对照（左侧）之间的显著差异。立体定向框架的使用对获得的结果有很大的影响。
根据三叉神经的躯体定位组织计数 c-Fos 免疫反应性细胞有助于更具体地检查硬脑膜化学刺激的效果。结果表明，IS 在顶叶上的应用导致了眼神经区域的激活。为了看到这种效果，使用利多卡因麻醉是必不可少的。总之，IS 在硬脑膜上的应用比 CFA 引起更短暂、更强烈的 c-Fos 激活，因此它可能为在啮齿动物中模拟急性偏头痛提供更好的方法。
