Changes of Meningeal Excitability Mediated by Corticotrigeminal Networks: A Link for the Endogenous Modulation of Migraine Pain
Changes of Meningeal Excitability Mediated by Corticotrigeminal Networks: A Link for the Endogenous Modulation of Migraine Pain
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DOI：
10.1523/jneurosci.3025-10.2010
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发表时间：
2010-10-27
影响因子：
5.3
通讯作者：
Villanueva, Luis
中科院分区：
文献类型：
--
作者：
Noseda, Rodrigo;Constandil, Luis;Villanueva, Luis
皮质兴奋性的改变与偏头痛的病理生理学有关。然而，皮质扩散性抑制（CSD）和头痛之间的关系尚未完全阐明。我们的目的是确定直接影响大鼠脑干三叉神经复合体（Sp 5C）脑膜伤害性感受的离皮质神经网络。投射到脑干的皮质区域首先通过从接收直接脑膜输入的Sp 5C区域的逆行追踪来识别。然后将顺行示踪剂注射到这些皮质区域，以确定Sp 5C中下行轴突终末场的精确模式。下行皮质投射到脑干区域，由三叉神经眼分支支配，起源于对侧岛叶（Ins）和初级躯体感觉（S1）皮质，并分别终止于Sp 5C的I-II和III-V层。在另一组实验中，电生理记录同时在Ins，SI或初级视觉皮层（V1）和Sp 5C神经元中进行。将KCl微量注射到这些皮层区域以测试CSD对脑膜伤害性感受的影响。在Ins和SI中启动的CSD分别引起脑膜诱发反应的易化和抑制。在VI区触发的CSD对Ins和SI皮层的影响不同，增强或抑制脑膜诱发的Sp 5C反应，而不影响皮肤诱发的伤害性反应。我们的数据表明，“自上而下”的影响，从偏侧区域内的INS和SI选择性地影响内感受性（脑膜）外感受性（皮肤）伤害性输入到Sp 5C。这种离皮质影响可能有助于发展偏头痛的地形定位和疼痛调谐在攻击期间。
Alterations in cortical excitability are implicated in the pathophysiology of migraine. However, the relationship between cortical spreading depression (CSD) and headache has not been fully elucidated. We aimed to identify the corticofugal networks that directly influence meningeal nociception in the brainstem trigeminocervical complex (Sp5C) of the rat. Cortical areas projecting to the brainstem were first identified by retrograde tracing from Sp5C areas that receive direct meningeal inputs. Anterograde tracers were then injected into these cortical areas to determine the precise pattern of descending axonal terminal fields in the Sp5C. Descending cortical projections to brainstem areas innervated by the ophthalmic branch of the trigeminal nerve originate contralaterally from insular (Ins) and primary somatosensory (S1) cortices and terminate in laminae I-II and III-V of the Sp5C, respectively. In another set of experiments, electrophysiological recordings were simultaneously performed in Ins, SI or primary visual cortex (V1), and Sp5C neurons. KCl was microinjected into such cortical areas to test the effects of CSD on meningeal nociception. CSD initiated in Ins and SI induced facilitation and inhibition of meningeal-evoked responses, respectively. CSD triggered in VI affects differently Ins and SI cortices, enhancing or inhibiting meningeal-evoked responses of Sp5C, without affecting cutaneous-evoked nociceptive responses. Our data suggest that "top-down" influences from lateralized areas within Ins and SI selectively affect interoceptive (meningeal) over exteroceptive (cutaneous) nociceptive inputs onto Sp5C. Such corticofugal influences could contribute to the development of migraine pain in terms of both topographic localization and pain tuning during an attack.