Istituto Nazionale di Ricovero e Cura dell'Anziano a carattere scientifico, IRCCS-INRCA, Ancona, Italy.
Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Neurobiol Dis. 2023 May;180:106072. doi: 10.1016/j.nbd.2023.106072. Epub 2023 Mar 11.
The implications of neurogenic inflammation and neuroinflammation in the pathophysiology of migraine have been clearly demonstrated in preclinical migraine models involving several sites relevant in the trigemino-vascular system, including dural vessels and trigeminal endings, the trigeminal ganglion, the trigeminal nucleus caudalis as well as central trigeminal pain processing structures. In this context, a relevant role has been attributed over the years to some sensory and parasympathetic neuropeptides, in particular calcitonin gene neuropeptide, vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Several preclinical and clinical lines of evidence also support the implication of the potent vasodilator and messenger molecule nitric oxide in migraine pathophysiology. All these molecules are involved in vasodilation of the intracranial vasculature, as well as in the peripheral and central sensitization of the trigeminal system. At meningeal level, the engagement of some immune cells of innate immunity, including mast-cells and dendritic cells, and their mediators, has been observed in preclinical migraine models of neurogenic inflammation in response to sensory neuropeptides release due to trigemino-vascular system activation. In the context of neuroinflammatory events implicated in migraine pathogenesis, also activated glial cells in the peripheral and central structures processing trigeminal nociceptive signals seem to play a relevant role. Finally, cortical spreading depression, the pathophysiological substrate of migraine aura, has been reported to be associated with inflammatory mechanisms such as pro-inflammatory cytokine upregulation and intracellular signalling. Reactive astrocytosis consequent to cortical spreading depression is linked to an upregulation of these inflammatory markers. The present review summarizes current findings on the roles of immune cells and inflammatory responses in the pathophysiology of migraine and their possible exploitation in the view of innovative disease-modifying strategies.
神经源性炎症和神经炎症在偏头痛的病理生理学中的意义在涉及三叉神经血管系统中几个相关部位的临床前偏头痛模型中得到了明确证明，包括硬脑膜血管和三叉神经末梢、三叉神经节、尾状核以及中央三叉神经疼痛处理结构。在这种情况下，多年来，一些感觉和副交感神经肽，特别是降钙素基因相关肽、血管活性肠肽和垂体腺苷酸环化酶激活肽，被认为具有重要作用。一些临床前和临床证据也支持强力血管扩张剂和信使分子一氧化氮在偏头痛病理生理学中的作用。所有这些分子都参与颅内血管的扩张，以及三叉神经系统的外周和中枢敏化。在脑膜水平，在神经源性炎症的临床前偏头痛模型中观察到先天免疫的一些免疫细胞，包括肥大细胞和树突状细胞及其介质，对感觉神经肽的释放作出反应，这是由于三叉神经血管系统的激活。在偏头痛发病机制中涉及的神经炎症事件的背景下，处理三叉神经伤害性信号的外周和中枢结构中激活的神经胶质细胞似乎也起着重要作用。最后，偏头痛先兆的病理生理学基础皮质扩散性抑制与炎症机制有关，如促炎细胞因子的上调和细胞内信号转导。皮质扩散性抑制继发的反应性星形胶质细胞增生与这些炎症标志物的上调有关。本综述总结了目前关于免疫细胞和炎症反应在偏头痛病理生理学中的作用的研究结果，并探讨了它们在创新的疾病修饰策略中的可能应用。
