No abstract

Recent studies have suggested that abnormalities of dopamine and trace amines (tyramine, octopamine, and synephrine), products of tyrosine metabolism, may constitute the metabolic events that predispose to the occurrence of cluster headache (CH) and migraine attacks. This hypothesis is supported by the following evidences: the discovery of trace amine associated receptors (TAARs), expressed on the olfactory epithelium, amigdala, hypothalamus, periacqueductal gray, and the biochemical anomalies of dopamine and trace amines. The possible effects of these biochemical abnormalities on TAARs and dopamine receptors, located in different areas of CNS, may explain the behaviour (restlessness, anxiety and, at times, hypersexuality) and the autonomic signs during the painful attacks of CH, and the premonitory symptoms of migraine crisis (thirst, craving, yawning, alteration of smell, depression etc.).

We briefly summarise biochemical anomalies of serotonin, norepinephrine, glutamic and aspartic acids, the main neurotransmitters of inhibitory and excitatory neuronal circuitries, found in primary headaches and their relationship with pathogenesis of migraine and cluster headache (CH). In addition, the high levels of circulating tyramine, octopamine and synephrine (elusive amines), recently reported in both migraine types and CH, are discussed in relation to the other "classic" amines findings. In particular it is suggested how abnormal levels of elusive amines may participate in the pathophysiology of migraine and CH acting through their specific trace amine receptors and alpha and beta receptors. The possible hypothesis that emerges from the analysis of these biochemical findings is that an imbalance of systems, with opposite neurophysiological functions related to the pain and other yet unknown functions, may constitute the biochemical phenotype of migraine with and without aura, and CH.

This study suggest that there is a change in responsiveness to dopaminergic stimulation during the day. The less effective dopaminergic response in afternoon depends on pharmacodynamic factors and not only on peripheral and central levodopa pharmacokinetic.

Migraine with aura (MwA) sufferers, at times, need specific treatments. This is the case when the auras are frequent, prolonged and cause anxiety and distress. Abnormal release of glutamate, which may trigger auras, and abnormal platelet behaviour, which constitutes a possible predisposing factor to MwA, are possible targets for MwA-specific prophylactic therapy. Here we present results obtained using lamotrigine (two open trials), an agent known to inhibit glutamate release, and picotamide, an antiplatelet drug, in the prophylactic treatment of MwA sufferers. Lamotrigine significantly reduced the frequency of MwA attacks, and picotamide together with lamotrigine reduced the duration and/or the occurrence of auras. In comparison to lamotrigine, the therapy with picotamide may have some advantages such as the use of the therapeutic dose from the first day of treatment (lamotrigine needs one month or more to reach such a dose) and the possibility to prevent cerebral ischaemic events and migraine stroke, a rare but severe complication of MwA attacks.