• neuropeptides;
  • cerebral circulation;
  • cranial vessels;
  • cranial nerves;
  • pain;
  • cluster headache;
  • autonomic


Various possible pathophysiological mechanisms to explain the pain in cluster headache are reviewed. Several locations for the initiation of pain along the primary afferent pathways in cranial nerves are discussed, together with the local mechanisms that might be responsible. These include neurogenic inflammation of large cranial vessels, irritation of vascular pain fibres by compression of dilated vessels in bony canals, and irritative foci in or around cranial sensory ganglia. In particular, recent neuroanatomical and pharmacological findings on nociceptive innervation of the intracranial segment of the internal carotid artery are commented upon. The possibilities for referred pain to explain the location of pain is illustrated. Evidence for involvement of central pain modulatory systems in the pain production is discussed. Finally a synthesis is made of the probable peripheral and central pain mechanisms in the disease.