Sensory nerves in man and their role in primary headaches.

The sensory innervation of intracranial vessels originate in the trigeminal ganglion and comprise the following signal substances; calcitonin gene-related peptide (CGRP), substance P, neurokinin A, pituitary adenylate cyclase activating peptide (PACAP) and nitric oxide (NO). Studies in patients have revealed a clear association between head pain and the release of CGRP. In cluster headache and in a case of chronic paroxysmal headache there is in addition release of vasoactive intestinal peptide (VIP), which was associated with the facial symptoms (nasal congestion, rhinorrhea). In parallel with triptan administration, acting via 5-HT(1B/1D) receptors, head pain subside and neuropeptide release normalise. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches.