Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura

Cephalalgia ◽  
2010 ◽  
Vol 30 (10) ◽  
pp. 1179-1186 ◽  
Author(s):  
Jakob Møller Hansen ◽  
Anne Werner Hauge ◽  
Jes Olesen ◽  
Messoud Ashina
Keyword(s):  
Migraine With Aura ◽  
Migraine Headache ◽  
Migraine Without Aura ◽  
Familial Hemiplegic Migraine ◽  
Calcitonin Gene Related Peptide ◽  
Hemiplegic Migraine ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Post Infusion ◽  
Migraine Pathogenesis

Introduction: Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP infusion triggers delayed migraine-like attacks in patients with migraine without aura (MO). In contrast to patients with MO, in prior studies patients with familial hemiplegic migraine (FHM) did not report more migraine-like attacks compared to controls. Whether CGRP triggers migraine in patients with typical (non-hemiplegic) migraine with aura is (MA) unknown. In the present study we examined the migraine inducing effect of CGRP infusion in patients suffering from MA and healthy controls. Methods: Fourteen patients suffering exclusively from migraine with typical aura (MA) and 11 healthy volunteers received a continuous intravenous infusion of 1.5 µg/min CGRP over 20 minutes. Headache and other migraine symptoms were scored every 10 minutes for one hour and self recorded hourly thereafter and until 13 hours post-infusion. Results: CGRP infusion induced significantly more delayed headaches in MA patients (12 out of 14) than in controls (2 out of 11) ( p = 0.001). Furthermore, significantly more MA patients (57%; 8 out of 14) fulfilled criteria for an experimentally induced migraine attack after CGRP than controls (0%; 0 out of 11) ( P = 0.003). Four patients (28%) reported aura symptoms after CGRP infusion. Conclusion: CGRP triggered migraine-like attacks without aura in patients suffering exclusively from MA. It also triggered a typical aura in 28% of the patients. These data indicate similar neurobiological pathways responsible for triggering migraine headache in MA and MO patients, and suggest differences between MA/MO and FHM.

scholarly journals Migraine: Calcium Channels and Glia

2021 ◽  
Vol 22 (5) ◽  
pp. 2688
Author(s):  
Marta Kowalska ◽  
Michał Prendecki ◽  
Thomas Piekut ◽  
Wojciech Kozubski ◽  
Jolanta Dorszewska
Keyword(s):  
Migraine With Aura ◽  
Migraine Without Aura ◽  
Spreading Depression ◽  
Adult Population ◽  
Familial Hemiplegic Migraine ◽  
Trigeminovascular System ◽  
Hemiplegic Migraine ◽  
Monogenic Form ◽  
Calcitonin Gene

Migraine is a common neurological disease that affects about 11% of the adult population. The disease is divided into two main clinical subtypes: migraine with aura and migraine without aura. According to the neurovascular theory of migraine, the activation of the trigeminovascular system (TGVS) and the release of numerous neuropeptides, including calcitonin gene-related peptide (CGRP) are involved in headache pathogenesis. TGVS can be activated by cortical spreading depression (CSD), a phenomenon responsible for the aura. The mechanism of CSD, stemming in part from aberrant interactions between neurons and glia have been studied in models of familial hemiplegic migraine (FHM), a rare monogenic form of migraine with aura. The present review focuses on those interactions, especially as seen in FHM type 1, a variant of the disease caused by a mutation in CACNA1A, which encodes the α1A subunit of the P/Q-type voltage-gated calcium channel.

Immunohistochemical characterization of calcitonin gene-related peptide in the trigeminal system of the familial hemiplegic migraine 1 knock-in mouse

Cephalalgia ◽  
2011 ◽  
Vol 31 (13) ◽  
pp. 1368-1380 ◽  
Author(s):  
Rammya Mathew ◽  
Anna P Andreou ◽  
Linda Chami ◽  
Astrid Bergerot ◽  
Arn MJM van den Maagdenberg ◽  
...  
Keyword(s):  
Familial Hemiplegic Migraine ◽  
Calcitonin Gene Related Peptide ◽  
Control Group ◽  
Cell Diameter ◽  
Trigeminal Ganglia ◽  
Wild Type ◽  
Hemiplegic Migraine ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Significant Difference

Introduction: Familial hemiplegic migraine type 1 (FHM-1) is caused by mutations in the CACNA1A gene, with the R192Q mutation being the most common. Elevated calcitonin gene-related peptide (CGRP) levels in acute migraine and clinical trials using CGRP receptor antagonists suggest CGRP-related mechanisms are important in migraine. Methods: Wild-type and R192Q knock-in mice were anaesthetized and perfused. Using immunohistochemical staining, the expression of CGRP in the trigeminocervical complex (TCC) and in the trigeminal and dorsal root ganglia was characterized. Results: There was a 38% reduction in the percentage of CGRP-immunoreactive cells in the trigeminal ganglia ( p < 0.001) of R192Q knock-in mice compared to wild-type animals. The size distribution profile of CGRP-immunoreactive cells within the trigeminal ganglia demonstrated no significant difference in cell diameter between the two groups ( p ≥ 0.56). CGRP expression was also reduced in thoracic ganglia of R192Q knock-in mice (21% vs. 27% in wild-type group; p < 0.05), but not in other ganglia. In addition, decreased CGRP immunoreactivity was observed in the superficial laminae of the TCC in R192Q knock-in mice, when compared to the control group ( p < 0.005). Conclusion: The data demonstrates that the FHM-1 CACNA1A mutation alters CGRP expression in the trigeminal ganglion and TCC. This suggests further study of these animals is warranted to characterize better the role of these mutations in the neurobiology of migraine.

Cortical Spreading Depression Does Not Result in the Release of Calcitonin Gene-Related Peptide into the External Jugular Vein of the Cat: Relevance to Human Migraine

Cephalalgia ◽  
1993 ◽  
Vol 13 (3) ◽  
pp. 180-183 ◽  
Author(s):  
Richard D Piper ◽  
Lars Edvinsson ◽  
Rolf Ekman ◽  
Geoffrey A Lambert
Keyword(s):  
Migraine With Aura ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Jugular Vein ◽  
Calcitonin Gene Related Peptide ◽  
External Jugular Vein ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Vasoactive Peptide ◽  
Stimulation Of

There is circumstantial evidence that cortical spreading depression (SD) may account for the scotoma and the “spreading cortical oligemia” seen during migraine with aura. It has been shown that calcitonin gene-related peptide (CGRP) is increased in blood taken from the external jugular vein (EJV) in humans during migraine and after stimulation of the trigeminal ganglion. To test the hypothesis that cortical SD may elevate the concentration of this vasoactive peptide in the EJV during migraine, we have measured its concentration in the external jugular vein of cats during cortical SD. This study demonstrates that SD has no effect on the concentration of CGRP either during the passage of a wave of spreading depression across the cortex or, 60 min later, during the period of post-SD cortical oligemia.

A Review of the Potential Receptors of Migraine with a Special Emphasis on CGRP to Develop an Ideal Antimigraine Drug

2020 ◽  
Vol 14 (1) ◽  
pp. 11-26
Author(s):  
Krishna P. Naduchamy ◽  
Varadarajan Parthasarathy
Keyword(s):  
Migraine Headache ◽  
Transient Receptor Potential ◽  
Calcitonin Gene Related Peptide ◽  
Present Review ◽  
Transient Receptor Potential Vanilloid ◽  
Cgrp Receptor ◽  
Target Proteins ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Study Results

Background and Objective: Migraine is a neurovascular syndrome associated with unilateral, throbbing headache accompanied with nausea, vomiting and photo/phonophobia. Several proteins are involved in the etiopathogenesis of migraine headache. The aim of the present review is to give an insight into the various target proteins involved in migraine headache pertaining to the development of a potential anti-migraine drug molecule. Proteins/receptors such as serotonin (5-HT), Calcitonin Gene Related Peptide (CGRP), Transient Receptor Potential Vanilloid (TRPV1), cannabinoid, glutamate, opioid and histamine receptors play various roles in migraine. The nature of the proteins, their types, binding partner membrane proteins and the consequences of the reactions produced have been discussed. The studies conducted on animals and humans with the above mentioned target proteins/receptors and the results obtained have also been reviewed. Conclusion: Calcitonin Gene Related Peptide (CGRP), a G protein coupled receptor (GPCR) significantly contributed to the progression of migraine. CGRP antagonist inhibits the release of CGRP from trigeminal neurons of trigeminal ganglion. Based on the study results, the present review suggests that the inhibition of CGRP receptor might be a successful way to treat migraine headache. Currently, researchers across the world are focussing their attention towards the development of novel molecules to treat migraine headache by targeting CGRP receptor which can be attributed to its specificity among the several proteins involved in migraine.

Sumatriptan Causes Parallel Decrease in Plasma Calcitonin Gene-Related Peptide (CGRP) Concentration and Migraine Headache During Nitroglycerin Induced Migraine Attack

Cephalalgia ◽  
2005 ◽  
Vol 25 (3) ◽  
pp. 179-183 ◽  
Author(s):  
G Juhasz ◽  
T Zsombok ◽  
B Jakab ◽  
J Nemeth ◽  
J Szolcsanyi ◽  
...  
Keyword(s):  
Migraine Attack ◽  
Migraine Headache ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Headache Intensity ◽  
Cgrp Release ◽  
Calcitonin Gene ◽  
Positive Correlations ◽  
Induced Changes ◽  
Main Effects

Sumatriptan-induced changes in plasma calcitonin gene-related peptide (CGRP) concentration and headache intensity were investigated in 19 female migraineurs during nitroglycerin-induced migraine attack. Sumatriptan nasal spray was administered 120 min after the onset of the attack. Blood samples were obtained immediately before and 60 min after sumatriptan administration. In those subjects whose migraine attack improved considerably 60 min after the treatment the plasma CGRP concentration decreased significantly ( P < 0.05). In contrast, plasma CGRP concentration failed to change in patients whose headache did not improve. In addition, plasma CGRP concentrations showed significant positive correlations with the headache scores both 60 and 120 min after sumatriptan administration ( P < 0.05). According to our results plasma CGRP concentration decreases parallel to headache intensity during sumatriptan treatment and this decrease in CGRP predicts effectiveness of antimigraine drug therapy. This supports that one of the main effects of triptans is to decrease CGRP release.

The Genetics of Migraine Without Aura and Migraine With Aura

Cephalalgia ◽  
1993 ◽  
Vol 13 (4) ◽  
pp. 245-248 ◽  
Author(s):  
Michael Bjørn Russell ◽  
Jes Olesen
Keyword(s):  
Migraine With Aura ◽  
Migraine Without Aura ◽  
Familial Aggregation ◽  
Familial Hemiplegic Migraine ◽  
Hemiplegic Migraine ◽  
Future Studies ◽  
Progressive Ataxia ◽  
Reduced Penetrance ◽  
Genetically Determined ◽  
Selection Of

Studies of twins, spouses and familial aggregation strongly suggest that migraine without aura (MO) and migraine with aura (MA) are genetically determined. The mode of inheritance is most likely multifactorial in both MO and MA. However, autosomal dominant inheritance with reduced penetrance cannot be excluded in either MO or MA. At present the only evidence for genetic heterogeneity of MA is familial hemiplegic migraine with slowly progressive ataxia. This phenomenon can also be explained by linkage of different genes. All existing studies have been characterized by one or more of the following methodologic shortcomings: selection of probands from clinic populations, information obtained by questionnaire, family history obtained through probands, insufficient description of the attacks, lack of distinction between MO and MA. Useful strategies for future studies of migraine genetics are discussed.

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