[Both neurogenic and vascular causes of primary headache]

The cerebral circulation is innervated by sympathetic, parasympathetic and sensory nerves which store a number of neurotransmitters. The significance of these for primary headache has been evaluated. A clear association between head pain and the release of calcitonin gene-related peptide (CGRP) was demonstrated. In cluster headache and in chronic paroxysmal hemicrania, there was additionally a release of vasoactive intestinal peptide (VIP) in association with facial symptoms (nasal congestion, rhinorrhea). Upon treatment with sumatriptan, head pain subsided and neuropeptide release normalized. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headache.