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

Calcitonin Gene-Related Peptide (CGRP) And Cluster Headache

Andrea Carmine Belin, C. Ran, L. Edvinsson
Published 2020 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP receptor complex have recently taken center stage as therapeutic targets for primary headaches, such as migraine. Multiple CGRP and CGRP receptor monoclonal antibodies, as well as small molecule antagonists (gepants) are on their way constituting a new frontier of migraine and possibly CH medication. During a CH attack, there is an activation of the trigeminal-autonomic reflex with the release of CGRP, and inversely if CGRP is administered to a CH patient in an active disease phase, it triggers an attack. Increased levels of CGRP have been found in ipsilateral jugular vein blood during the active phase of CH. This process is hypothesized to have a key role in the intense pain perception and in the associated distinctive vasodilation. So far, clinical tests of CGRP antibodies have been inconclusive in CH patients. This review summarizes the current state of knowledge on the role of CGRP in CH pathology, and as a target for future treatments.
This paper references
10.1016/S0165-6147(99)01347-4
RAMPs: accessory proteins for seven transmembrane domain receptors.
S. Foord (1999)
10.1016/0301-0082(94)E0017-B
Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves
C. Maggi (1995)
10.1002/ana.22292
Evidence for a vascular factor in migraine
M. Asghar (2011)
10.1507/ENDOCRJ1954.36.409
Calcitonin gene-related peptide in the human hypothalamus.
K. Takahashi (1989)
10.1007/s10072-019-03786-7
Anti-CGRP in cluster headache therapy
L. Giani (2019)
10.1523/JNEUROSCI.08-07-02468.1988
Enrichment of a vasoactive neuropeptide (calcitonin gene related peptide) in the trigeminal sensory projection to the intracranial arteries
T. O’Connor (1988)
10.1016/j.brainres.2014.11.031
Localization of CGRP, CGRP receptor, PACAP and glutamate in trigeminal ganglion. Relation to the blood–brain barrier
Sajedeh Eftekhari (2015)
10.1111/head.13583
Targeting CGRP for the Prevention of Migraine and Cluster Headache: A Narrative Review
H. Yuan (2019)
10.1111/j.1526-4610.1994.hed3407394.x
Peripheral and Central Trigeminovascular Activation in Cat is Blocked by the Serotonin (5HT)‐I D Receptor Agonist 311C90
P. Goadsby (1994)
10.1530/EJE.0.1330017
Calcitonin, calcitonin gene-related peptide, adrenomedullin and amylin: homologous peptides, separate receptors and overlapping biological actions.
R. Muff (1995)
10.1186/s10194-019-0992-1
Effects of monoclonal antagonist antibodies on calcitonin gene-related peptide receptor function and trafficking
R. Manoukian (2019)
10.1016/S1474-4422(02)00104-7
Pathophysiology of cluster headache: a trigeminal autonomic cephalgia
P. Goadsby (2002)
10.1007/s10072-017-2907-8
The role of anti-CGRP antibodies in the pathophysiology of primary headaches
P. Barbanti (2017)
10.1111/j.1526-4610.2009.01523.x
Elevated Saliva Calcitonin Gene‐Related Peptide Levels During Acute Migraine Predict Therapeutic Response to Rizatriptan
R. Cady (2009)
10.1124/pr.54.2.233
International Union of Pharmacology. XXXII. The Mammalian Calcitonin Gene-Related Peptides, Adrenomedullin, Amylin, and Calcitonin Receptors
D. Poyner (2002)
10.1126/science.aae0189
Feature: Will antibodies finally put an end to migraines?
E. Underwood (2016)
10.1038/304129A0
Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing
M. Rosenfeld (1983)
10.1111/bph.14075
Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25
D. Hay (2018)
10.1001/ARCHNEUR.1971.00490030051005
Histamine and serotonin in cluster headache.
M. Anthony (1971)
10.1007/s10072-017-3101-8
Calcitonin gene-related peptide antagonism and cluster headache: an emerging new treatment
Håkan Ashina (2017)
10.1016/j.jpain.2009.03.018
Genetic enhancement of calcitonin gene-related Peptide-induced central sensitization to mechanical stimuli in mice.
B. Marquez de Prado (2009)
10.1016/0166-2236(85)90050-5
Functional role of perivascular peptides in the control of cerebral circulation
L. Edvinsson (1985)
[Cluster headache].
Y. Takase (2005)
10.1523/JNEUROSCI.1727-09.2009
Role of Calcitonin Gene-Related Peptide in Light-Aversive Behavior: Implications for Migraine
A. Recober (2009)
10.1177/0333102419867282
Erenumab (AMG 334), a monoclonal antagonist antibody against the canonical CGRP receptor, does not impair vasodilatory or contractile responses to other vasoactive agents in human isolated cranial arteries
L. Ohlsson (2019)
10.1074/JBC.M107323200
Agonist-promoted Internalization of a Ternary Complex between Calcitonin Receptor-like Receptor, Receptor Activity-modifying Protein 1 (RAMP1), and β-Arrestin*
S. Hilairet (2001)
10.1177/0333102415625614
Migraine biomarkers in cerebrospinal fluid: A systematic review and meta-analysis
Robin M. van Dongen (2017)
10.1139/Y95-152
Clinical perspectives of calcitonin gene related peptide pharmacology.
G. Feuerstein (1995)
10.1177/0333102409351807
Measurement of vasoactive neuropeptides in biological materials: Problems and pitfalls from 30 years of experience and novel future approaches
L. Edvinsson (2010)
10.1016/0140-6736(90)90040-C
Plasma CGRP in acute myocardial infarction
J. Mair (1990)
10.1186/1129-2377-14-S1-P89
Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system
S. Eftekhari (2013)
10.1177/0333102417728873
Distribution of CGRP and CGRP receptor components in the rat brain
K. Warfvinge (2019)
10.1111/j.1749-6632.1992.tb22779.x
Calcitonin Gene—Related Peptide in Inflammatory Bowel Disease and Experimentally Induced Colitis
V. Eysselein (1992)
Cluster Headache : Investigating severity of pain , suicidality , personal burden , access to effective treatment , and demographics among a large International survey sample
Song Guo (2017)
10.1016/S0140-6736(19)32504-8
Targeting calcitonin gene-related peptide: a new era in migraine therapy
A. Charles (2019)
10.1177/0333102419856640
Calcitonin gene-related peptide levels in tear fluid are elevated in migraine patients compared to healthy controls
K. Kamm (2019)
10.1016/j.neuroscience.2011.10.055
Distribution of vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, nitric oxide synthase, and their receptors in human and rat sphenopalatine ganglion
A. Csáti (2012)
10.1001/jamaneurol.2018.1675
Effect of Infusion of Calcitonin Gene-Related Peptide on Cluster Headache Attacks: A Randomized Clinical Trial
A. L. Vollesen (2018)
10.1177/0333102418815506
Sleep in cluster headache revisited: Results from a controlled actigraphic study
N. Lund (2019)
10.1016/j.brainres.2007.12.028
Calcitonin gene-related peptide stimulation of nitric oxide synthesis and release from trigeminal ganglion glial cells
J. Li (2008)
10.1093/BRAIN/117.3.427
Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies.
P. J. Goadsby (1994)
10.1111/j.1526-4610.2007.00854.x
Neuron–Glia Signaling in Trigeminal Ganglion: Implications for Migraine Pathology
Srikanth Thalakoti (2007)
10.1074/jbc.R700011200
Acid-sensing Ion Channels in Sensory Perception*
E. Lingueglia (2007)
10.1016/0196-9781(91)90022-H
Calcitonin gene-related peptide, neurokinin A and substance P: Effects on Nociception and neurogenic inflammation in human skin and temporal muscle
U. Pedersen-Bjergaard (1991)
10.1016/S0165-1838(99)00024-7
Messenger molecules and receptor mRNA in the human trigeminal ganglion.
J. Tajti (1999)
Joint 1994 Wolff Award Presentation. Peripheral and central trigeminovascular activation in cat is blocked by the serotonin (5HT)-1D receptor agonist 311C90.
P. J. Goadsby (1994)
10.1177/2515816319879886
Involvement of CGRP receptor RAMP1 in cluster headache: A Swedish case-control study
Julia M. Michalska (2019)
10.1210/EDRV-17-5-533
Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials.
S. Wimalawansa (1996)
10.1016/J.BRAINRESREV.2004.11.006
The role of mast cells in migraine pathophysiology
T. Theoharides (2005)
10.1177/0333102410362122
Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries
L. Edvinsson (2010)
10.1212/WNL.62.3.516
Specific hypothalamic activation during a spontaneous cluster headache attack
T. Sprenger (2004)
10.1111/j.1526-4610.2006.00294.x
Salivary Levels of CGRP and VIP in Rhinosinusitis and Migraine Patients
Jaime L. Bellamy (2006)
10.1111/j.1468-2982.2008.01558.x
Comparison of CGRP and NO Responses in the Human Peripheral Microcirculation of Migraine and Control Subjects
M-L Edvinsson (2008)
10.1046/j.1468-2982.1993.1305318.x
Prevalence of Headache in Tulp's Observationes Medicae (1641) with a Description of Cluster Headache
P. Koehler (1993)
10.1016/j.neuroscience.2010.05.016
Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion
S. Eftekhari (2010)
10.1177/0333102419884943
Characterisation of the calcitonin gene-related peptide receptor antagonists ubrogepant and atogepant in human isolated coronary, cerebral and middle meningeal arteries
E. Rubio-Beltrán (2019)
10.1016/0304-3940(85)90166-1
Perivascular peptides relax cerebral arteries concomitant with stimulation of cyclic adenosine monophosphate accumulation or release of an endothelium-derived relaxing factor in the cat
L. Edvinsson (1985)
10.1038/s41582-018-0003-1
CGRP as the target of new migraine therapies — successful translation from bench to clinic
L. Edvinsson (2018)
10.1016/J.MOLMED.2006.11.005
Recent advances in understanding migraine mechanisms, molecules and therapeutics.
P. Goadsby (2007)
10.1074/jbc.M606338200
Post-endocytic Sorting of Calcitonin Receptor-like Receptor and Receptor Activity-modifying Protein 1*
G. Cottrell (2007)
Teva Halts Development of Fremanezumab | NeurologyLive . NeurologyLive . 2019
J. Payesko
10.1016/0092-8674(87)90202-9
Splice commitment dictates neuron-specific alternative RNA processing in calcitonin/CGRP gene expression
S. Leff (1987)
10.1007/s00441-002-0616-x
Calcitonin receptor-like receptor: identification and distribution in human peripheral tissues
S. Hagner (2002)
10.1111/apha.12213
Differential localization and characterization of functional calcitonin gene‐related peptide receptors in human subcutaneous arteries
L. Edvinsson (2014)
10.1038/298240A0
Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products
S. Amara (1982)
10.2147/TCRM.S159690
Once-monthly galcanezumab for the prevention of migraine in adults: an evidence-based descriptive review and potential place in therapy
C. Lupi (2019)
10.1007/s10565-017-9399-4
Exogenous CGRP upregulates profibrogenic growth factors through PKC/JNK signaling pathway in kidney proximal tubular cells
S. P. Yoon (2017)
10.1111/j.1526-4610.2006.00611.x
Gene Expression Profiling in Cluster Headache: A Pilot Microarray Study
C. Sjöstrand (2006)
10.1007/BF01466734
Protein size and cerebrospinal fluid composition
K. Felgenhauer (2005)
Hypothalamic activation in cluster headache
A. May (1998)
10.1016/j.gene.2012.11.053
Association study of the calcitonin gene-related polypeptide-alpha (CALCA) and the receptor activity modifying 1 (RAMP1) genes with migraine.
H. Sutherland (2013)
10.1016/S0165-6147(00)89093-8
Pharmacology of receptors for calcitonin gene-related peptide and amylin.
D. Poyner (1995)
10.1212/WNL.0000000000007787
Cluster headache
A. Steinberg (2019)
10.1046/j.1468-2982.1990.1001039.x
Sensory Neuropeptides (Substance P, Calcitonin Gene-Related Peptide) and Vasoactive Intestinal Polypeptide in Human Saliva: Their Pattern in Migraine and Cluster Headache
M. Nicolodi (1990)
10.1007/s12031-015-0567-9
Preliminary Transcriptome Analysis in Lymphoblasts from Cluster Headache and Bipolar Disorder Patients Implicates Dysregulation of Circadian and Serotonergic Genes
Marta Costa (2015)
10.1046/j.1468-2982.1997.1703166.x
Release of Histamine from Dural Mast Cells by Substance P and Calcitonin Gene-Related Peptide
A. Ottosson (1997)
10.1124/MOL.55.6.1054
The amino terminus of receptor activity modifying proteins is a critical determinant of glycosylation state and ligand binding of calcitonin receptor-like receptor.
N. J. Fraser (1999)
10.1038/jhh.2009.68
Haplotype-based case–control study of receptor (calcitonin) activity-modifying protein-1 gene in cerebral infarction
T. Nakazato (2010)
10.1111/j.1476-5381.1985.tb11107.x
Inflammatory oedema induced by synergism between calcitonin gene‐related peptide (CGRP) and mediators of increased vascular permeability
S. Brain (1985)
10.1002/cne.21607
Calcitonin receptor‐like receptor (CLR), receptor activity‐modifying protein 1 (RAMP1), and calcitonin gene‐related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: Differences between peripheral and central CGRP receptor distribution
J. K. Lennerz (2008)
Joint
P. J. Goadsby (1994)
10.1186/s10194-015-0575-8
Experimental inflammation following dural application of complete Freund’s adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage
C. Lundblad (2015)
Teva Halts Development of Fremanezumab|NeurologyLive. NeurologyLive
J Payesko
10.1038/313054A0
Calcitonin gene-related peptide is a potent vasodilator
S. Brain (1985)
10.1177/0333102410368444
Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura
J. B. Hansen (2010)
10.1046/j.1468-2982.2002.00310.x
Cgrp May Play A Causative Role in Migraine
L. Lassen (2002)
10.1016/0304-3959(94)00097-X
Increase in plasma calcitonin gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster headache attack
M. Fanciullacci (1995)
10.1523/JNEUROSCI.23-03-00807.2003
Stimulation of the Calcitonin Gene-Related Peptide Enhancer by Mitogen-Activated Protein Kinases and Repression by an Antimigraine Drug in Trigeminal Ganglia Neurons
P. Durham (2003)
10.1016/S0304-3959(00)00232-3
Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks
M. Ashina (2000)
10.1615/CRITREVNEUROBIOL.V11.I2-3.40
Amylin, calcitonin gene-related peptide, calcitonin, and adrenomedullin: a peptide superfamily.
S. Wimalawansa (1997)
10.1046/j.1468-2982.1993.1305309.x
A Review of Hormonal Findings in Cluster Headache. Evidence for Hypothalamic Involvement
M. Leone (1993)
10.1016/J.LFS.2006.01.003
Characterisation of CGRP receptors in the human isolated middle meningeal artery.
S. Gupta (2006)
Primary headache disorders : Five new things
P. J. Goadsby (2019)
10.1111/head.12559
Association of RAMP1 rs7590387 With the Risk of Migraine Transformation Into Medication Overuse Headache
S. Cargnin (2015)
10.1016/0014-5793(85)80820-6
A second human calcitonin/CGRP gene
P. Steenbergh (1985)
10.1111/j.1468-2982.2008.01592.x
The Incidence and Prevalence of Cluster Headache: A Meta-Analysis of Population-Based Studies
M. Fischera (2008)
10.1038/30666
RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor
L. M. McLatchie (1998)
10.1016/j.brainres.2011.11.058
Calcitonin gene-related peptide and its receptor components in the human sphenopalatine ganglion — Interaction with the sensory system
A. Csáti (2012)
10.1006/BBRC.1993.1451
Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma.
K. Kitamura (1993)
10.1113/EXPPHYSIOL.1987.SP003084
Biology of peptides from the calcitonin genes.
M. Zaidi (1987)
ff ects of monoclonal antagonist antibodies on calcitonin gene - related peptide receptor function and tra ffi cking
R. Manoukian (2019)
10.1046/j.1468-2982.1991.1104175.x
Pain, Tenderness, Wheal and Flare Induced by Substance-P, Bradykinin and 5-Hydroxytryptamine in Humans
K. Jensen (1991)
10.1054/npep.2000.0810
Involvement of cAMP-dependent protein kinase and pertussis toxin-sensitive G-proteins in CGRP mediated JNK activation in human neuroblastoma cell line
J. Disa (2000)
FDA just approved the first drug to prevent migraines. Here's the story of its discovery-and its limitations
E Underwood (2018)
10.1242/jcs.02783
Adrenomedullin and CGRP interact with endogenous calcitonin-receptor-like receptor in endothelial cells and induce its desensitisation by different mechanisms
L. Nikitenko (2006)
10.1021/BI020279R
The transmembrane domain of receptor-activity-modifying protein 1 is essential for the functional expression of a calcitonin gene-related peptide receptor.
Sarah Steiner (2002)
10.1002/ANA.410280213
Vasoactive peptide release in the extracerebral circulation of humans during migraine headache
P. J. Goadsby (1990)
10.1038/srep40218
Identifying a gene expression signature of cluster headache in blood
Else Eising (2017)
10.1177/0333102417731773
Cluster headache – clinical pattern and a new severity scale in a Swedish cohort
A. Steinberg (2018)
10.1074/jbc.273.32.20168
Activation of Phospholipase C-β1 via Gαq/11during Calcium Mobilization by Calcitonin Gene-related Peptide*
H. Drissi (1998)
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)
10.1016/S0149-7634(96)00023-1
Neuroanatomical Localization, Pharmacological Characterization and Functions of CGRP, Related Peptides and Their Receptors
D. Rossum (1997)
10.1002/ANA.410330109
The trigeminovascular system and migraine: Studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats
P. J. Goadsby (1993)
10.1007/s10072-018-3337-y
A new era in headache treatment
M. Vikelis (2018)
10.1177/0333102418765787
Molecular studies of CGRP and the CGRP family of peptides in the central nervous system
Erica R. Hendrikse (2019)
Aimovig : Dosage , side e ff ects , uses , and more
L. Slowiczek
FDA just approved the first drug to prevent migraines. Here’s the story of its discovery—and its limitations. Science 2018
E. Underwood (2018)
10.1111/j.1468-2982.2001.00245.x
Sensory Nerves in Man and Their Role in Primary Headaches
L. Edvinsson (2001)
10.1016/j.tips.2010.06.006
Regulation of signal transduction by calcitonin gene-related peptide receptors.
C. Walker (2010)
10.1186/s10194-017-0798-y
Screening of genetic variants in ADCYAP1R1, MME and 14q21 in a Swedish cluster headache cohort
C. Ran (2017)
10.1056/NEJMoa1813440
Trial of Galcanezumab in Prevention of Episodic Cluster Headache.
P. Goadsby (2019)
10.1074/jbc.M005604200
CGRP-RCP, a Novel Protein Required for Signal Transduction at Calcitonin Gene-related Peptide and Adrenomedullin Receptors*
B. Evans (2000)
10.1186/1471-2202-12-112
Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level
S. Eftekhari (2011)
10.1152/PHYSREV.00037.2003
Vascular actions of calcitonin gene-related peptide and adrenomedullin.
S. Brain (2004)
10.1002/ANA.410210503
Peptide‐containing nerve fibers in human cerebral arteries: Immunocytochemistry, radioimmunoassay and in vitro pharmacology
L. Edvinsson (1987)
10.1177/0333102419837154
Calcitonin-gene related peptide and disease activity in cluster headache
A. Snoer (2019)
10.1002/acn3.197
A second trigeminal CGRP receptor: function and expression of the AMY1 receptor
C. Walker (2015)
10.1007/s40263-019-00630-6
Pathophysiological Mechanisms in Migraine and the Identification of New Therapeutic Targets
K. Haanes (2019)
10.1083/jcb.200704053
Endothelin-converting enzyme-1 regulates endosomal sorting of calcitonin receptor-like receptor and β-arrestins
B. Padilla (2007)
10.1007/s11940-017-0463-4
Anti-CGRP Monoclonal Antibodies: the Next Era of Migraine Prevention?
A. R. Tso (2017)
10.1124/jpet.110.165993
Characterization of the Calcitonin Gene-Related Peptide Receptor Antagonist Telcagepant (MK-0974) in Human Isolated Coronary Arteries
K. Chan (2010)
10.1186/s10194-019-1055-3
C-fibers may modulate adjacent Aδ-fibers through axon-axon CGRP signaling at nodes of Ranvier in the trigeminal system
J. Edvinsson (2019)
10.1111/j.1526-4610.2012.02212.x
CGRP and NO in the Trigeminal System: Mechanisms and Role in Headache Generation
K. Messlinger (2012)
10.1186/s10194-016-0705-y
A genome-wide analysis in cluster headache points to neprilysin and PACAP receptor gene variants
E. Bacchelli (2016)
10.1016/S0140-6736(98)02470-2
Hypothalamic activation in cluster headache attacks
A. May (1998)
Chemosensitive afferent nerves in the regulation of gastric blood flow and protection.
P. Holzer (1995)
10.1177/0333102417738202
Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition
M. Arnold (2018)
10.1073/PNAS.84.23.8628
Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients.
G. Cooper (1987)



This paper is referenced by
Semantic Scholar Logo Some data provided by SemanticScholar