The pathogenesis of migraine, the third most frequent disease worldwide, is complex and multifaceted. Recent evidence suggests that this condition should be considered as a primary neurovascular disorder. The pathogenesis is sustained by a relative reduction of cerebral blood flow, which is then followed by reactive hyperaemia, sterile inflammation and hypersensitization of pain pathways. The leading triggers of the initial vasoconstriction entail both hereditary or acquired cerebrovascular disorders, namely local endothelial or smooth muscle dysfunction, arteriovenous malformations autoimmune and inflammatory disorders, along with cerebral microembolism. The existence of a potential relationship between platelet biology and migraine has been hypothesized more than 30 years ago, paving the way to a series of subsequent studies. Despite the clinical evidence that patients with essential thrombocythemia have a high frequency of headache symptoms, the epidemiological trials that have investigated the platelet count in patients with an accurate diagnosis of migraine failed to report significant associations. Conversely, several lines of evidence attest that serotonin metabolism is substantially impaired in migraine patients, thus contributing to trigger or enhance vasoconstriction and hypersensitization of neuronal elements. Although abnormalities of nitric oxide metabolism should be confirmed in larger studies, published data suggests that this compound may be effective to amplify the reactive vasodilatation that specifically follows the initial reduction of cerebral blood flow. Another plausible link between platelet biology and migraine is represented by inflammation. Increased release of several proinflammatory cytokines, especially interleukins 1, 6 and 8 and tumor necrosis factor-alpha, may occur after formation of platelet-leukocyte aggregates, and these mediators can further contribute to increase sterile inflammation in the brain and facilitate pain signalling.
Keywords: Headache; Migraine; Nitric Oxide; Pathogenesis; Platelets; Serotonin.
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