Online citations, reference lists, and bibliographies.
← Back to Search

The Trigeminovascular System And Migraine: Studies Characterizing Cerebrovascular And Neuropeptide Changes Seen In Humans And Cats

P. J. Goadsby, L. Edvinsson
Published 1993 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
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 on 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). These data characterize some aspects of the cerebrovascular physiology of the trigeminovascular system and demonstrate important interactions between this system and the effective antimigraine agents sumatriptan and dihydroergotamine and that such interactions can be represented in animal models.
This paper references
10.1016/0140-6736(91)90666-D
Oral sumatriptan in acute migraine
P. Goadsby (1991)
10.1016/0304-3940(90)90217-W
High-frequency stimulation of the facial nerve results in local cortical release of vasoactive intestinal polypeptide in the anesthetised cat
P. Goadsby (1990)
10.1038/jcbfm.1991.58
Chronic Trigeminal Ganglionectomy or Topical Capsaicin Application to Pial Vessels Attenuates Postocclusive Cortical Hyperemia but Does Not Influence Postischemic Hypoperfusion
R. Macfarlane (1991)
10.1093/BRAIN/114.2.1001
Stimulation of the superior sagittal sinus increases metabolic activity and blood flow in certain regions of the brainstem and upper cervical spinal cord of the cat.
P. J. Goadsby (1991)
10.1073/PNAS.83.15.5731
Calcitonin gene-related peptide: functional role in cerebrovascular regulation.
J. McCulloch (1986)
10.1111/j.1526-4610.1983.hed2306258.x
Brainstem Influences on the Cephalic Circulation: Experimental Data From Cat and Monkey of Relevance to the Mechanism of Migraine
J. Lance (1983)
10.1002/ANA.410280213
Vasoactive peptide release in the extracerebral circulation of humans during migraine headache
P. J. Goadsby (1990)
10.1007/BF00346363
Peptidergic innervation of the cerebral circulation. Role in subarachnoid hemorrhage in man
L. Edvinsson (2004)
10.1001/JAMA.1991.03460210077033
Treatment of acute migraine with subcutaneous sumatriptan.
R. Cady (1991)
10.3109/02688699008992720
Calcitonin gene-related peptide-LI in subarachnoid haemorrhage in man. Signs of activation of the trigemino-cerebrovascular system?
R. Juul (1990)
10.1002/ANA.410230214
Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system
P. J. Goadsby (1988)
10.1038/jcbfm.1981.24
Perivascular Substance P: Occurrence and Distribution in Mammalian Pial Vessels
R. Uddman (1981)
10.1016/0006-8993(85)90535-9
Extracranial vasodilatation mediated by vasoactive intestinal polypeptide (VIP)
P. Goadsby (1985)
10.1073/PNAS.86.4.1401
Trigeminovascular fibers increase blood flow in cortical gray matter by axon reflex-like mechanisms during acute severe hypertension or seizures.
D. Sakas (1989)
10.1016/0006-8993(86)90690-6
Stimulation of the Trigeminal ganglion increases flow in the extracerebral but not the cerebral circulation of the monkey
P. Goadsby (1986)
10.1046/j.1468-2982.1988.0801001.x
Flunarizine in Prophylaxis of Childhood Migraine: A Double-Blind, Placebo-Controlled, Crossover Study
Fulvio Sorge (1988)
10.1016/0165-1838(84)90053-5
The peripheral pathway for extracranial vasodilatation in the cat.
P. Goadsby (1984)
10.1002/CNE.902250204
Co‐localization of retrogradely transported wheat germ agglutinin and the putative neurotransmitter substance P within trigeminal ganglion cells projecting to cat middle cerebral artery
L. Y. Liu-Chen (1984)
10.1136/jnnp.46.7.611
Facial flushing after thermocoagulation of the Gasserian ganglion.
P. Drummond (1983)
10.1016/0006-8993(90)91211-X
Sphenopalatine ganglion stimulation increases regional cerebral blood flow independent of glucose utilization in the cat
P. Goadsby (1990)
10.1038/jcbfm.1988.145
Effect of Stimulation of the Sphenopalatine Ganglion on Cortical Blood Flow in the Rat
J. Seylaz (1988)
10.1038/jcbfm.1990.68
Selective Electrical Stimulation of Postganglionic Cerebrovascular Parasympathetic Nerve Fibers Originating from the Sphenopalatine Ganglion Enhances Cortical Blood Flow in the Rat
N. Suzuki (1990)
10.3171/JNS.1984.61.2.0307
Decreased carotid arterial resistance in cats in response to trigeminal stimulation.
G. Lambert (1984)
10.1016/0006-8993(88)90152-7
Comparative effects of stimulation of the trigeminal ganglion and the superior sagittal sinus on cerebral blood flow and evoked potentials in the cat
G. Lambert (1988)
10.1111/J.1748-1716.1990.TB08851.X
Effect on cortical blood flow of electrical stimulation of trigeminal cerebrovascular nerve fibres in the rat.
N. Suzuki (1990)
10.1016/0304-3940(85)90296-4
Innervation of the feline cerebral vasculature by nerve fibers containing calcitonin gene-related peptide: Trigeminal origin and co-existence with substance P
R. Uddman (1985)
10.1002/CNE.902230105
Trigeminal projections to supratentorial pial and dural blood vessels in cats demonstrated by horseradish peroxidase histochemistry
M. Mayberg (1984)
10.1159/000116759
A Randomized, Double-Blind Comparison of Sumatriptan and Cafergot in the Acute Treatment of Migraine
P. Humphrey (1991)
10.1038/jcbfm.1991.114
Parasympathetic Denervation of Rat Pial Vessels Significantly Increases Infarction Volume following Middle Cerebral Artery Occlusion
M. Kano (1991)
10.1016/0143-4179(90)90114-E
Stimulation of the superior sagittal sinus in the cat causes release of vasoactive peptides
A. Zagami (1990)
10.1080/01621459.1955.10501294
A Multiple Comparison Procedure for Comparing Several Treatments with a Control
C. Dunnett (1955)
10.1016/0169-2607(86)90060-X
An interactive, readily transportable program using a log/logit transformation for the analysis of radioimmunoassay data.
P. Goadsby (1986)



This paper is referenced by
10.1016/j.neubiorev.2017.05.001
Mast cells in neuroinflammation and brain disorders
E. Hendriksen (2017)
10.1097/NRL.0b013e3181663555
Headache and Pregnancy
Rukmini Menon (2008)
10.1007/s10072-009-0061-7
Neural substrate of depression during migraine
R. Burstein (2009)
10.1046/j.1468-2982.1995.015002136.x
Nocturnal Melatonin Excretion is Decreased in Patients With Migraine Without Aura Attacks Associated With Menses
J. Brun (1995)
10.1111/head.13154
Novel Therapeutic Targets Against Spreading Depression
Shih-Pin Chen (2017)
Responses of Trigeminal Ganglion Neurons to Electrical and Mechanical Stimulation of the Middle Meningeal Artery, Superior Sagittal Sinus and Transverse Sinus in Rats
K. Lee (1999)
10.1159/000061584
The Pharmacology and Mechanisms of Action of Rizatriptan
R. Hargreaves (2000)
Molecular Cloning and Pharmacology of Porcine 5-Hydroxytryptamine Receptors Relevant to the Study of Antimigraine Drugs
P. Bhalla (2002)
10.1016/S0028-3908(02)00008-4
Efficacy of the non-peptide CGRP receptor antagonist BIBN4096BS in blocking CGRP-induced dilations in human and bovine cerebral arteries: potential implications in acute migraine treatment
M. Moreno (2002)
10.1523/JNEUROSCI.3565-17.2018
Optogenetic Inhibition of CGRPα Sensory Neurons Reveals Their Distinct Roles in Neuropathic and Incisional Pain
Ashley M Cowie (2018)
10.1046/j.1526-4610.1997.3703174.x
Therapeutic Blockade of Greater Occipital and Supraorbital Nerves in Migraine Patients
C. Caputi (1997)
10.1016/j.jns.2009.02.326
The role of kynurenines in disorders of the central nervous system: Possibilities for neuroprotection
E. Vámos (2009)
10.1177/0333102412447701
Primary trigeminal afferents are the main source for stimulus-induced CGRP release into jugular vein blood and CSF
J. Hoffmann (2012)
10.1007/978-3-642-54922-9_32
Manuelle Lymphdrainage zur Behandlung verschiedener Kopfschmerzsyndrome
Günther Bringezu (2014)
10.1007/s004010051098
Peptidergic innervation of human cerebral blood vessels and saccular aneurysms
András Büki (1999)
The pharmacological management of migraine, part 1: overview and abortive therapy.
George Demaagd (2008)
10.1186/s12883-018-1193-2
A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine
A. Camporeale (2018)
Mass spectrometry-based characterization of cell-to-cell signaling molecules in the nervous system
N. Yang (2016)
10.1177/0333102418768095
CGRP – a target for acute therapy in migraine: Clinical data
Roberta Messina (2019)
10.1517/17460441.2013.826644
Discovery techniques for calcitonin gene-related peptide receptor antagonists for potential antimigraine therapies
S. Labruijere (2013)
zur Erlangung des akademischen Grades Doctor medicinae (Dr. med.)
Daniel Wolbergs (2015)
10.1155/2016/2059749
Cerebral Venous Thrombosis with Migraine-Like Headache and the Trigeminovascular System
Fábio A Nascimento (2016)
PII: S0304-3959(00)00478-4
Rami Burstein (2001)
10.1016/0304-3940(94)11203-U
Electrical stimulation of the Gasserian ganglion induces structural alterations of calcitonin gene-related peptide-immunoreactive perivascular sensory nerve terminals in the rat cerebral dura mater: a possible model of migraine headache
E. Knyihár-csillik (1995)
10.1212/WNL.0b013e3181f9631e
Calcitonin gene-related peptide receptor antagonists and triptans
P. Goadsby (2010)
10.1111/j.1460-9568.2006.04742.x
Nitric oxide regulation of calcitonin gene‐related peptide gene expression in rat trigeminal ganglia neurons
Jamie Bellamy (2006)
10.1038/sj.bjp.0704357
Characterization of the prostanoid receptor types involved in mediating calcitonin gene‐related peptide release from cultured rat trigeminal neurones
D. W. Jenkins (2001)
10.1016/S0014-2999(97)83028-2
The novel anti-migraine agent rizatriptan inhibits neurogenic dural vasodilation and extravasation.
D. Williamson (1997)
10.1017/S0317167100000147
Pathophysiology of migraine--new insights.
R. Hargreaves (1999)
Clinical Characteristics and Pathophysiological Mechanisms of Familial Migraine with and without Aura
M. Kallela (2000)
10.1124/MOL.59.6.1533
Adenosine A(1) receptor-mediated inhibition of protein kinase A-induced calcitonin gene-related peptide release from rat trigeminal neurons.
A. M. Carruthers (2001)
10.1080/17512433.2020.1774361
Cluster headache therapies: pharmacology and mode of action
Jasper Mecklenburg (2020)
See more
Semantic Scholar Logo Some data provided by SemanticScholar