Aspects on the Pathophysiology of Migraine and Cluster Headache

The specific cause of migraine headache remains unknown. Current theories suggest that the initiation of a migraine attack involves a primary CNS dysfunction with subsequent activation of the trigeminovascular system. Studies in patients have revealed a clear association between headache and the release of the neuropeptide calcitonin gene‐related peptide, probably from C fibres. In cluster headache and in a case of chronic paroxysmal headache there was in addition release of the parasympathetic neuropeptide vasoactive intestinal peptide, which was associated with headache, nasal congestion and rhinorrhea. Triptan administration, activating the 5‐HT1B/1D receptors, caused the headache to subside and the neuropeptide release to normalise. These data suggest the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches.