The pathogenesis of
migraine as well as
cluster headache (CH) is yet a debated question. In this review, we discuss the possible role of the of
tyrosine and
tryptophan metabolism in the pathogenesis of these primary
headaches. These include the abnormalities in the synthesis of
neurotransmitters: high level of DA, low level of NE and very elevated levels of
octopamine and
synephrine (
neuromodulators) in plasma of episodic
migraine without aura and CH patients. We hypothesize that the imbalance between the levels of
neurotransmitters and elusive
amines synthesis is due to a metabolic shift directing
tyrosine toward an increased
decarboxylase and reduced
hydroxylase enzyme activities. The metabolic shift of the
tyrosine is favored by a state of neuronal hyperexcitability and a reduced mitochondrial activity present in
migraine. In addition we present biochemical studies performed in chronic
migraine and chronic
tension-type headache patients to verify if the same anomalies of the
tyrosine and
tryptophan metabolism are present in these primary
headaches and, if so, their possible role in the chronicity process of CM and CTTH. The results show that important abnormalities of
tyrosine metabolism are present only in CM patients (very high plasma levels of DA, NE and
tryptamine).
Tryptamine plasma levels were found significantly lower in both CM and CTTH patients. In view of this, we propose that
migraine and, possibly, CH attacks derive from
neurotransmitter and
neuromodulator metabolic abnormalities in a hyperexcitable and hypoenergetic brain that spread from the frontal lobe, downstream, resulting in abnormally activated nuclei of the
pain matrix. The low
tryptamine plasma levels found in CM and CTTH patients suggest that these two primary
chronic headaches are characterized by a common insufficient serotoninergic control of the pain threshold.