The biochemistry of migraine: investigation of systems involving 5-hydroxytryptamine and magnesium

Although the pathogenesis of migraine remains to be fully elucidated, recent studies have implicated the involvement of the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) and also magnesium. This thesis has further explored the role of 5-HT and magnesium in migraine pathogenesis and also the effects of red wine, believed to trigger migraine in some individuals. Central serotonergic functioning was investigated in migraine and tension-type headache patients by neuroendocrine challenge test, using oral fenfluramine, which stimulates the release of 5-HT from hypothalamic neurones, causing a dose dependent release of prolactin from the pituitary. Plasma prolactin was significantly raised in tension-type headache patients compared with controls, suggesting a central serotonergic supersensitivity. Fenfluramine triggered a headache in most migraine and tension-type headache patients and headache scores positively correlated with prolactin response. Temperature, also under partial control by central 5-HT mechanisms, was significantly raised in migraine patients compared with controls. These findings suggest supersensitivity in the central 5-HT system in tension-type headache, but not in migraine, however, further investigation is required in migraineurs. Plasma prolactin and cortisol measurements were used to determine if red wine acts on 5-HT centrally. No changes were found following red wine administration in controls and migraineurs, suggesting it does not. Migraineurs exhibited significantly lower mean phenolsulphotransferase (PST) P and M levels compared with controls, levels in diet sensitive patients being further reduced compared with non-diet sensitive patients and controls. Red wine is known to inhibit PST in vitro. This research demonstrated that red wine also significantly inhibited PST P in vivo in controls. Urinary magnesium (Mg[sup]2+) excretion was found to be significantly increased during attack compared with migraineurs not in attack and controls. The effect of red wine on Mg[sup]2+ homeostasis was investigated in controls by examining the effects of red wine ingestion on serum Mg[sup]2+, which did not alter, and urinary Mg[sup]2+ levels which significantly increased, implying a general release of Mg[sup]2+ from body stores. However, this also occurred after vodka and white wine ingestion, suggesting this effect is not specific to red wine. Stress is a commonly quoted migraine precipitant. Urinary Mg[sup]2+ was investigated in controls when stressed and stress free, no significant difference was found. In conclusion, this thesis has provided many observations which require further research. A significant supersensitivity in the central serotonergic system has been demonstrated in tension-type headache, but not in migraine. Furthermore, centraI release of 5-HT has been shown not to be involved in the mechanism of a red wine induced migraine attack. This thesis has also provided the first evidence of a reduced PST M and P activity in specifically red wine sensitive migraineurs. Further indication as to the general depletion of magnesium from the body during a migraine attack has also been provided.