Biochemical Tryptophan Anomalies and Painful Attacks
The main product of tryptophan hydroxylase is serotonin (5-HT), whereas tryptamine is the neuromodulator that derives from the decarboxylase product of tryptophan. The involvement of 5-HT in migraine was hypothesized more than 50 years ago when F. Sicuteri demonstrated the occurrence of significantly elevated levels in urine of 5-hydroxyindoleacetic acid, stable metabolite of 5-HT, during migraine attacks. Since this, numerous studies have attempted to clarify the possible biochemical anomalies of 5-HT in migraine, mainly utilizing platelets as a model of serotonergic neurons. Studies from our laboratory have shown that the levels of platelet 5-HT fluctuate in female migraine sufferers differently from those in healthy woman in the different phases of the menses and, more importantly, the levels of the indole decrease significantly in the luteal phase in menstrual migraine before the painful attacks. The reason why the levels of 5-HT drop before the attack is not known. However, it is possible to conceive that there may occur a biochemical shift of tryptophan metabolism toward decarboxylation rather than hydroxylation, therein favoring an increase in the synthesis of tryptamine and a reduction in the synthesis 5-HT, respectively, in the synaptic clefts of neurons of the ANS nuclei of the brain stem.