Headache Center of Villa Margherita Neurologic Clinic, 36057, Arcugnano, Vicenza, Italy.
Neurol Sci. 2010 Jun;31 Suppl 1:S1-7. doi: 10.1007/s10072-010-0267-8.
Here, in this review, we present our hypothesis of the migraine pathogenesis. We believe that migraine attacks derive from a top-down dysfunctional process that initiates in a hyperexcitable and hypoenergetic brain in the frontal lobe and downstream in abnormally activated nuclei of the pain matrix. This hypothesis derived from the results of the biochemical studies, mainly generated from our laboratory, on the possible metabolic shifts of tyrosine toward an activation of decarboxylase enzyme activity with an increased synthesis of traces amines, i.e. tyr, oct and syn, and an unphysiological synthesis of noradrenalin and dopamine. This metabolic shift is possibly favored by the reduced mitochondrial energy and high levels of glutamate in CNS of migraine patients. The unbalanced levels of neurotransmitters (DA and NE) and neuromodulators (tyr, oct and syn) in the synaptic dopaminergic and noradrenergic clefts of the pain matrix may activate, downstream, the trigeminal system that releases calcitonin gene-related G peptide. This induces the formation of an inflammatory soup, the sensitization of first trigeminal neuron and the migraine attack.
在这里，我们提出了偏头痛发病机制的假说。我们认为，偏头痛发作源于自上而下的功能障碍过程，该过程起始于额叶过度兴奋和能量不足的大脑，以及下游异常激活的疼痛矩阵核。这一假说源自我们实验室关于酪氨酸可能发生的生化研究结果，主要涉及酶活性的脱羧作用增加，微量胺（即 tyr、oct 和 syn）的合成增加，以及去甲肾上腺素和多巴胺的异常合成。这种代谢转变可能受到偏头痛患者中枢神经系统中线粒体能量减少和谷氨酸水平升高的影响。疼痛矩阵中的突触多巴胺能和去甲肾上腺素能裂中的神经递质（DA 和 NE）和神经调质（tyr、oct 和 syn）的失衡水平可能会激活下游的三叉神经系统，释放降钙素基因相关肽。这会引起炎症汤的形成，第一三叉神经神经元的敏化和偏头痛的发作。
