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Pathogenesis of migraine: from neurotransmitters to neuromodulators and beyond

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Abstract

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.

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  1. Headache Center of Villa Margherita Neurologic Clinic, 36057, Arcugnano, Vicenza, Italy

    G. D’Andrea

  2. Research and Innovation (R&I) S.p.A, Padua, Italy

    A. Leon

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  1. G. D’Andrea
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  2. A. Leon
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D’Andrea, G., Leon, A. Pathogenesis of migraine: from neurotransmitters to neuromodulators and beyond. Neurol Sci 31 (Suppl 1), 1–7 (2010). https://doi.org/10.1007/s10072-010-0267-8

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