Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
J Neurosci. 2010 Oct 27;30(43):14420-9. doi: 10.1523/JNEUROSCI.3025-10.2010.
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, S1 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 S1 induced facilitation and inhibition of meningeal-evoked responses, respectively. CSD triggered in V1 affects differently Ins and S1 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 S1 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.
皮层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）与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脑干三叉神经颈复合体（Sp5C）脑膜伤害感受的皮质传出网络。首先通过从接收直接脑膜传入的 Sp5C 区域逆行追踪来鉴定投射到脑干的皮质区域。然后将顺行示踪剂注入这些皮质区域，以确定 Sp5C 中下行轴突终末场的精确模式。起源于三叉神经眼支支配的脑干区域的皮质下投射对侧来自岛叶（Ins）和初级体感（S1）皮质，分别终止于 Sp5C 的 I-II 层和 III-V 层。在另一组实验中，在 Ins、S1 或初级视觉皮层（V1）和 Sp5C 神经元中同时进行电生理记录。将 KCl 微注射到这些皮质区域，以测试 CSD 对脑膜伤害感受的影响。Ins 和 S1 中引发的 CSD 分别诱导脑膜诱发反应的易化和抑制。在 V1 中引发的 CSD 以不同的方式影响 Ins 和 S1 皮质，增强或抑制 Sp5C 的脑膜诱发反应，而不影响皮肤诱发的伤害性反应。我们的数据表明，来自 Ins 和 S1 中侧化区域的“自上而下”影响选择性地影响 Sp5C 上的内感受（脑膜）伤害性输入，而不是外感受（皮肤）伤害性输入。这种皮质传出影响可能有助于偏头痛疼痛的发展，无论是在发作期间的地形定位还是疼痛调谐方面。
