Pathogenesis of Migraine

Role of Neuromodulators

Giovanni D'Andrea, MD; Antonello D'Arrigo, PhD; Maurizio Dalle Carbonare, PhD; Alberta Leon, PhD


Headache. 2012;52(7):1155-1163. 

In This Article

Elusive Amines, Premonitory Symptoms, and Migraine Attack

The modalities by which stressful agents within the brain may cause the painful attacks in migraine is not known; however, according to the theory put forth by Welch, the first pathophysiological event may occur in the orbitofrontal part of the frontal lobe and, thereafter, downstream to the limbic, amygdale, and hypothalamic-connected areas of the CNS. Although still partly speculative, an increasing body of clinical, biochemical, and functional studies now support this theory. Migraine attacks are, very often, preceded by premonitory symptoms, such as hyperosmia, yawning, mood changes, anxiety, food craving, sexual excitement, fatigue, and emotional lability, which last from minutes to days.[31,32] These symptoms are considered markers of activation of the above-mentioned brain areas, and, therefore, it is logical to attribute the first phase of the migraine attacks within these areas.[33] Further support also derives from evidences showing that, in these same brain areas, TAARs and dopamine receptors are abundantly distributed. The activation of these receptors is likely reflected in the high levels of dopamine and elusive amines found in plasma and platelets of migraine without aura sufferers during headache-free periods.[34,35]


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