Headache Center, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia 2, I-80138, Naples, Italy.
MRI Research Centre SUN-FISM, University of Campania, "Luigi Vanvitelli", Caserta, Italy.
J Headache Pain. 2019 May 3;20(1):46. doi: 10.1186/s10194-019-1002-3.
Despite the growing body of advanced studies investigating the neuronal correlates of pain processing in patients with migraine without aura (MwoA), only few similar studies have been conducted in patients with migraine with aura (MwA). Therefore, we aimed to explore the functional brain response to trigeminal noxious heat stimulation in patients with MwA.
Seventeen patients with MwA and 15 age- and sex-matched healthy controls (HC) underwent whole-brain blood oxygen level-dependent (BOLD) fMRI during trigeminal noxious heat stimulation. To examine the specificity of any observed differences between patients with MwA and HC, the functional response of neural pathways to trigeminal noxious heat stimulation in patients with MwA was compared with 18 patients with MwoA. Secondary analyses investigated the correlations between BOLD signal changes and clinical parameters of migraine severity.
We observed a robust cortical and subcortical pattern of BOLD response to trigeminal noxious heat stimulation across all participants. Patients with MwA showed a significantly increased activity in higher cortical areas known to be part of a distributed network involved in advanced visual processing, including lingual gyrus, inferior parietal lobule, inferior frontal gyrus and medial frontal gyrus. Moreover, a significantly greater cerebellar activation was observed in patients with MwA when compared with both patients with MwA and HC. Interestingly, no correlations were found between migraine severity parameters and magnitude of BOLD response in patients with MwA.
Our findings, characterized by abnormal visual pathway response to trigeminal noxious heat stimulation, support the role of a functional integration between visual and trigeminal pain networks in the pathophysiological mechanisms underlying migraine with aura. Moreover, they expand the concept of "neurolimbic-pain network" as a model of MwoA including both limbic dysfunction and cortical dys-excitability. Indeed, we suggest a model of "neurolimbic-visual-pain network" in MwA patients, characterized by dysfunctional correlations between pain-modulating circuits not only with the cortical limbic areas but with advanced visual areas as well. Furthermore, the abnormal cerebellar response to trigeminal noxious heat stimulation may suggest a dysfunctional cerebellar inhibitory control on thalamic sensory gating, impinging on the advanced visual processing cortical areas in patients with MwA.
尽管越来越多的高级研究调查了无先兆偏头痛（MwoA）患者疼痛处理的神经元相关性，但仅有少数类似的研究在有先兆偏头痛（MwA）患者中进行。因此，我们旨在探讨 MwA 患者三叉神经痛觉刺激的功能性脑反应。
17 例 MwA 患者和 15 名年龄和性别匹配的健康对照者（HC）在三叉神经痛觉刺激期间接受全脑血氧水平依赖（BOLD） fMRI 检查。为了检验在 MwA 患者和 HC 之间观察到的任何差异的特异性，将 MwA 患者三叉神经痛觉刺激的神经通路功能反应与 18 例 MwoA 患者进行了比较。次要分析研究了 BOLD 信号变化与偏头痛严重程度临床参数之间的相关性。
我们观察到所有参与者三叉神经痛觉刺激的皮质和皮质下 BOLD 反应呈现出一种强烈的模式。与 MwoA 患者相比，MwA 患者在已知参与高级视觉处理的分布式网络的较高皮质区域表现出显著增加的活动，包括舌回、下顶叶、下额回和内侧额回。此外，与 MwA 患者和 HC 相比，MwA 患者的小脑激活显著增加。有趣的是，在 MwA 患者中，偏头痛严重程度参数与 BOLD 反应幅度之间未发现相关性。
我们的研究结果表明，三叉神经痛觉刺激异常的视觉通路反应支持视觉和三叉神经痛觉网络之间功能整合在有先兆偏头痛病理生理机制中的作用。此外，它们扩展了“神经边缘-疼痛网络”作为包括边缘功能障碍和皮质兴奋过度的 MwoA 模型的概念。事实上，我们建议在 MwA 患者中建立“神经边缘-视觉-疼痛网络”模型，其特征是疼痛调节回路与皮质边缘区域之间不仅存在功能失调的相关性，而且与高级视觉区域之间也存在功能失调的相关性。此外，三叉神经痛觉刺激异常的小脑反应可能表明小脑对丘脑感觉门控的抑制控制功能障碍，影响 MwA 患者的高级视觉处理皮质区域。
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