The trigeminovascular system and migraine: Studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats

Abstract

Both clinical and physiological consideration of migraine suggests that the pathophysiology of the syndrome is intimately linked to the trigeminal innervation of the cranial vessels, the trigeminovascular system. Studies were conducted in cats and humans to examine the interaction of these systems with the effective acute antimigraine drugs dihydroergotamine and sumatriptan. In the animal studies cats were anesthetized and prepared for routine physiological monitoring as well as for blood sampling from the external jugular veins. Cerebral blood flow was monitored continuously using laser Doppler flowmetry and the effect of trigeminal ganglion stimulation on both cerebral blood flow and jugular vein peptide levels determined prior to and after administration of either sumatriptan or dihydroergotamine. Stimulation of the trigeminal ganglion led to a frequency-dependent increase in cerebral blood flow, with a mean maximum of 43 +/- 9% at a stimulus frequency of 20 per second. There was a marked reduction in these responses by some 50% after administration of either sumatriptan or dihydroergotamine. Trigeminal ganglion stimulation at a frequency of 5 per second also led to a release into the cranial circulation of calcitonin gene-related peptide (CGRP), with the level rising from 67 +/- 3 to 82 +/- 5 pmol/liter on the side of stimulation. These increases were also markedly antagonized by both sumatriptan and dihydroergotamine. Human studies were conducted as part of the overall evaluation of sumatriptan for the treatment of acute migraine. In 7 of 8 patients responding to subcutaneous sumatriptan administration, elevated CGRP levels (60 +/- 8 pmol/liter) were normalized, with the headache being relieved (40 +/- 8 pmol/liter).(ABSTRACT TRUNCATED AT 250 WORDS)

Botulinum toxin type-A therapy in cluster headache: an open study

“…It has also been reported to be effective in the therapy for migraine [4,5] or chronic migraine [6][7][8]. On analogy to migraine, during CH attacks an activation of the trigemino-vascular system and an elevation of calcitonin gene-related peptide (CGRP) in the jugular venous blood [9] have been observed. These suspected similarities in pathophysiology were the rationale to investigate the use of BTX-A for CH therapy.…”

Headache

“…The CGRP is elevated in acute migraine, 27 and its levels normalized by sumatriptan. 28 These observations led to the development of specific CGRP receptor antagonists, 28 such as olcegepant (BIBN4096BS) 29 and telcagepant. 30,31 Intravenous olcegepant is effective in acute migraine, 32 as is oral telcagepant.…”

Migraine and Cardiovascular Disease

“…According to this view, the pain is understood as a combination of altered perception (due to peripheral or central sensitization) of stimuli, as well as the activation of a feed-forward neurovascular dilator mechanism in the first division of the trigeminal nerve 22 . The brainstem activation would induce a pro-noniceptive state and also lead to deficits in the autonomic vascular control 20 .…”

“…According to this view, the pain is understood as a combination of altered perception (due to peripheral or central sensitization) of stimuli, as well as the activation of a feed-forward neurovascular dilator mechanism in the first division of the trigeminal nerve 22 . The brainstem activation would induce a pro-noniceptive state and also lead to deficits in the autonomic vascular control 20 .An alternative theory proposes that spreading depression of cortical activity (cortical spreading depression -CSD) is the first neurological event happening in migraine 23 . CSD would explain the migraine aura and would cause further activation of trigeminovascular afferents ultimately associated with inflammation at the level of the extra-cephalic blood vessels 24 .…”