IN 1961, Sicuteri, Testi, and Anselmi1 demonstrated that the excretion in the urine of 5-hydroxyindoleacetic acid (5HIAA), the principal catabolite of serotonin (5-hydroxytryptamine, 5HT), was increased during some attacks of migraine headache. This was confirmed by Curran, Hinterberger, and Lance2 in the majority of patients studied whereas Curzon, Theaker, and Phillips3 were able to find such a correlation in only two out of nine migrainous subjects.
Interest in the possible relationship of serotonin to the migraine syndrome had quickened following Sicuteri's preliminary trial of methysergide, a serotonin "antagonist," in the treatment of migraine.4 The value of methysergide maleate has since been established, although the mechanism of its action is still unexplained.5 Kimball, Friedman, and Vallejo6 were unable to produce headache in migrainous subjects by the injection of serotonin or its precursor 5-hydroxytryptophan. Indeed they found that injection of these substances relieved spontaneous migraine headaches. These
Anthony M, Hinterberger H, Lance JW. Plasma Serotonin in Migraine and Stress. Arch Neurol. 1967;16(5):544-552. doi:10.1001/archneur.1967.00470230096013