Cgrp May Play A Causative Role in Migraine

Lassen, LH; Haderslev, P A; Jacobsen, V B; Iversen, Helle K.; Sperling, Bjørn; Olesen, Jes

doi:10.1046/j.1468-2982.2002.00310.x

Cited by 897 publications

(776 citation statements)

References 29 publications

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“…CGRP is believed to play an important role in the genesis and maintenance of inflammation and pain associated with both migraine and TMJ pathology (Lassen et al, 2002;Juhasz et al, 2003;Lobbezoo et al, 2004). In this study, we used an in vivo model of TMJ inflammation to investigate the effect of Theobroma cacao extract on trigeminal nerve activation and CGRP release.…”

Section: Discussionmentioning

confidence: 99%

Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract

Abbey

Patil

Vause

et al. 2008

Journal of Ethnopharmacology

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Ethnopharmacological relevance-Cocoa bean preparations were first used by the ancient Maya and Aztec civilizations of South America to treat a variety of medical ailments involving the cardiovascular, gastrointestinal, and nervous systems. Diets rich in foods containing abundant polyphenols, as found in cocoa, underlie the protective effects reported in chronic inflammatory diseases. Release of calcitonin gene-related peptide (CGRP) from trigeminal nerves promotes inflammation in peripheral tissues and nociception.Aim of the study-To determine whether a methanol extract of Theobroma cacao L. (Sterculiaceae) beans enriched for polyphenols could inhibit CGRP expression, both an in vitro and an in vivo approach was taken.Results-Treatment of rat trigeminal ganglia cultures with depolarizing stimuli caused a significant increase in CGRP release that was repressed by pretreatment with Theobroma cacao extract. Pretreatment with Theobroma cacao was also shown to block the KCl-and capsaicin-stimulated increases in intracellular calcium. Next, the effects of Theobroma cacao on CGRP levels were determined using an in vivo model of temporomandibular joint (TMJ) inflammation. Capsaicin injection into the TMJ capsule caused an ipsilateral decrease in CGRP levels. Theobroma cacao extract injected into the TMJ capsule 24 h prior to capsaicin treatment repressed the stimulatory effects of capsaicin.Conclusions-Our results demonstrate that Theobroma cacao extract can repress stimulated CGRP release by a mechanism that likely involves blockage of calcium channel activity. Furthermore, our findings suggest that the beneficial effects of diets rich in cocoa may include suppression of sensory trigeminal nerve activation.

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Section: Discussionmentioning

confidence: 99%

Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract

Abbey

Patil

Vause

et al. 2008

Journal of Ethnopharmacology

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“…Furthermore, plasma concentrations of CGRP, but not of SP, were elevated during the headache phase of migraine [64] and cluster headache [65]. There is evidence that intravenous infusion of CGRP produces a migraine-like headache [66], and intravenous infusion of nitric oxide produces a migraine-like headache with an associated increase in plasma CGRP levels [67]. In migraine patients baseline CGRP levels were considerably higher, and the changes in plasma CGRP levels during migraine attacks were significantly correlated with the headache intensity [67].…”

Section: Migraine and Neurogenic Inflammationmentioning

confidence: 99%

CGRP and migraine: neurogenic inflammation revisited

Geppetti

Capone²,

Trevisani

et al. 2005

J Headache Pain

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The term 'neurogenic inflammation' refers to a series of proinflammatory responses produced by the stimulation of peripheral terminals of a subset of primary sensory neurons and the subsequent release of the neuropeptides, calcitonin gene-related peptide (CGRP) and the tachykinins, substance P (SP) and neurokinin A (NKA) [1]. The neurons that produce inflammation comprise a heterogeneous cell population with A-delta and C fibres, defined as polymodal nociceptors because they sense thermal, chemical and high-threshold mechanical stimuli. These neurons express on their plasma membrane a large panel of excitatory and inhibitory receptors and channels, and some of these signalling proteins have been successfully used as targets for analgesic or anti-inflammatory drugs. Among the channels expressed on peptidergic primary sensory neurons, transient receptor potential vanilloid-1 (TRPV1) [2], activated by the xenobiotic capsaicin, the pungent ingredient of plants of the genus Capsicum, is of paramount importance. Capsaicin produces burning pain by stimulating TRPV1 and by releasing sensory neuropeptides causes neurogenic inflammation. However, high concentrations/doses of capsaicin have the ability, after an initial excitatory phase, to desensitise the sensory nerve terminals, thus reducing the transmission of sensory/pain signals and abolishing neurogenic inflammation [3, 4]. This specific feature of capsaicin has greatly contributed to define the role of this subset of sensory nerves in pathophysiological models of human diseases and has been Pierangelo Geppetti Jay Guido Capone Marcello Trevisani Paola Nicoletti Giovanni Zagli Maria Rosalia Tola Abstract For more than a century neurogenic inflammation has been proposed to have a role in various human diseases. The present review will cover the conceptual steps of the itinerary that has led to the conclusion that neurogenic inflammation is important in migraine. Of particular relevance for the object of this article is the observation that tachykinindependent neurogenic inflammatory responses are evident in rodents, but much less pronounced or absent in other mammal species, including man, whereas neurogenic vasodilatation, most likely mediated by CGRP, occurs in most mammalian species and also in man. Recent evidence that a CGRP receptor antagonist was effective in the treatment of migraine attack supports the hypothesis that neurogenic vasodilatation is a major underlying mechanism of migraine.

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“…Elevated levels of CGRP, but not of other neuropeptides, were found in the external jugular vein during the headache phase of migraine and normalized in parallel with headache improvement [22,23]. Furthermore, infusion of human CGRP was found to trigger a migraine attack in susceptible individuals, while normalization of CGRP levels were obtained after migraine treatment with triptans [24][25][26]. These findings provided new insight into a putative role of CGRP in the pathophysiology of migraine, opening new pathways for therapeutic intervention.…”

Section: Pathophysiologymentioning

confidence: 81%

“…Positron emission tomography (PET) imaging studies in healthy subjects and migraineurs demonstrated that CGRP-RAs do not act centrally [104]. Similarly, intravenous administration of CGRP can induce migraine in susceptible individuals without crossing the BBB [24]. Antibodies consist of larger size molecules that are even less likely to cross the BBB.…”

Section: Blood-brain Barriermentioning

confidence: 99%

Targeting CGRP: A New Era for Migraine Treatment

Goldberg

Silberstein

2015

CNS Drugs

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Migraine is a highly prevalent headache disease that typically affects patients during their most productive years. Despite significant progress in understanding the underlying pathophysiology of this disorder, its treatment so far continues to depend on drugs that, in their majority, were not specifically designed for this purpose. The neuropeptide calcitonin gene-related peptide (CGRP) has been indicated as playing a critical role in the central and peripheral pathways leading to a migraine attack. It is not surprising that drugs designed to specifically block its action are gaining remarkable attention from researchers in the field with, at least so far, a safe risk profile. In this article, we highlight the evolution from older traditional treatments to the innovative CGRP target drugs that are revolutionizing the way to approach this debilitating neurological disease. We provide a brief introduction on pathophysiology of migraine and details on the characteristic, function, and localization of CGRP to then focus on CGRP receptor antagonists (CGRP-RAs) and CGRP monoclonal antibodies (CGRP mAbs). Key PointsThe neuropeptide calcitonin gene-related peptide (CGRP) has been indicated as playing a critical role in the central and peripheral pathways leading to a migraine attack.Targeting CGRP as a specific therapeutic tool for migraine may offer similar or even better efficacy than currently available treatments without the vasoconstrictive risk factors.Further studies are necessary to determine the exact role of CGRP receptor antagonists and CGRP monoclonal antibodies in migraine with aura, allodynia, and photophobia.

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Cgrp May Play A Causative Role in Migraine

Cited by 897 publications

References 29 publications

Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract

Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract

CGRP and migraine: neurogenic inflammation revisited

Targeting CGRP: A New Era for Migraine Treatment

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