• migraine;
  • cluster headache;
  • CGRP;
  • VIP;
  • trigeminovascular reflex;
  • autonomic nerves

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