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https://www.readbyqxmd.com/read/29237283/ghrelin-attenuated-hyperalgesia-induced-by-chronic-nitroglycerin-cgrp-and-trpv1-as-targets-for-migraine-management
#1
Fereshteh Farajdokht, Gisou Mohaddes, Dariush Shanehbandi, Pouran Karimi, Shirin Babri
Background According to the neurovascular theory of migraine, activation of the trigeminovascular system contributes to the development of migraine. This study examined the effects of chronic intraperitoneal ghrelin (150 µg/kg) treatment on the development of chronic migraine induced by intermittent injection of nitroglycerin 10 mg/kg. Methods Baseline and post-drug (2 h following nitroglycerin injection) mechanical and thermal sensitivity were assessed by von Frey hair and tail immersion tests, respectively on days 1, 3, 5, 7, 9 and 11...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29226741/side-effects-associated-with-current-and-prospective-antimigraine-pharmacotherapies
#2
Abimael González-Hernández, Bruno A Marichal-Cancino, Antoinette MaassenVanDenBrink, Carlos M Villalón
Migraine is a neurovascular disorder. Current acute specific antimigraine pharmacotherapies target trigeminovascular 5-HT1B/1D, 5-HT1F and CGRP receptors but, unfortunately, they induce some cardiovascular and central side effects that lead to poor treatment adherence/compliance. Therefore, new antimigraine drugs are being explored. Areas covered. This review considers the adverse (or potential) side effects produced by current and prospective antimigraine drugs, including medication overuse headache (MOH) produced by ergots and triptans, the side effects observed in clinical trials for the new gepants and CGRP antibodies, and a section discussing the potential effects resulting from disruption of the cardiovascular CGRPergic neurotransmission...
December 9, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29200178/induction-of-chronic-migraine-phenotypes-in-a-rat-model-after-environmental-irritant-exposure
#3
Phillip Edward Kunkler, LuJuan Zhang, Philip Lee Johnson, Gerry Stephen Oxford, Joyce Harts Hurley
Air pollution is linked to increased emergency room visits for headache and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well-understood. We previously reported that chronic environmental irritant exposure sensitizes the trigeminovascular system response to nasal administration of environmental irritants. Here, we examine whether chronic environmental irritant exposure induces migraine behavioral phenotypes. Male rats were exposed to acrolein, a TRPA1 agonist, or room air by inhalation for 4 days prior to meningeal blood flow measurements, periorbital cutaneous sensory testing or other behavioral testing...
December 1, 2017: Pain
https://www.readbyqxmd.com/read/29174963/diagnosis-pathophysiology-and-management-of-cluster-headache
#4
REVIEW
Jan Hoffmann, Arne May
Cluster headache is a trigeminal autonomic cephalalgia characterised by extremely painful, strictly unilateral, short-lasting headache attacks accompanied by ipsilateral autonomic symptoms or the sense of restlessness and agitation, or both. The severity of the disorder has major effects on the patient's quality of life and, in some cases, might lead to suicidal ideation. Cluster headache is now thought to involve a synchronised abnormal activity in the hypothalamus, the trigeminovascular system, and the autonomic nervous system...
November 23, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/29131327/cgrp-and-ptx3-as-predictors-of-efficacy-of-onabotulinumtoxin-type-a-in-chronic-migraine-an-observational-study
#5
Clara Domínguez, Alba Vieites-Prado, María Pérez-Mato, Tomás Sobrino, Xiana Rodríguez-Osorio, Ana López, Francisco Campos, Francisco Martínez, José Castillo, Rogelio Leira
OBJECTIVE: The aim of this study is to find a relation between several biomarkers in peripheral blood and outcome after treatment with onabotulinumtoxin A (OnabotA). BACKGROUND: OnabotA is an effective treatment in chronic migraine (CM). Different studies have tried to find predictors of response to treatment, either with clinical characteristics, neuroimaging features, or molecular biomarkers; however, it is still not possible to predict the individual outcome...
November 13, 2017: Headache
https://www.readbyqxmd.com/read/29082826/gender-aspects-of-cgrp-in-migraine
#6
Alejandro Labastida-Ramírez, Eloísa Rubio-Beltrán, Carlos M Villalón, Antoinette MaassenVanDenBrink
Background Migraine is two to three times more prevalent in women than in men, but the mechanisms involved in this gender disparity are still poorly understood. In this respect, calcitonin gene-related peptide (CGRP) plays a key role in migraine pathophysiology and, more recently, the functional interactions between ovarian steroid hormones, CGRP and the trigeminovascular system have been recognized and studied in more detail. Aims To provide an overview of CGRP studies that have addressed gender differences utilizing animal and human migraine preclinical research models to highlight how the female trigeminovascular system responds differently in the presence of varying ovarian steroid hormones...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29050521/glutamate-receptor-antagonists-with-the-potential-for-migraine-treatment
#7
Anna Ferrari, Cecilia Rustichelli, Carlo Baraldi
Preclinical, clinical, and other (e.g., genetic) evidence support the concept that migraine susceptibility may at least partially result from a glutamatergic system disorder. Therefore, the receptors of the glutamatergic system are considered relatively new targets for investigational drugs to treat migraine. Investigational and established glutamate receptor antagonists (GluRAs) have been shown to possess antinociceptive properties in preclinical models of trigeminovascular nociception and have been evaluated in clinical trials...
October 27, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29022756/soluble-guanylyl-cyclase-is-a-critical-regulator-of-migraine-associated-pain
#8
Manel Ben Aissa, Alycia F Tipton, Zachariah Bertels, Ronak Gandhi, Laura S Moye, Madeline Novack, Brian M Bennett, Yueting Wang, Vladislav Litosh, Sue H Lee, Irina N Gaisina, Gregory Rj Thatcher, Amynah A Pradhan
Background Nitric oxide (NO) has been heavily implicated in migraine. Nitroglycerin is a prototypic NO-donor, and triggers migraine in humans. However, nitroglycerin also induces oxidative/nitrosative stress and is a source of peroxynitrite - factors previously linked with migraine etiology. Soluble guanylyl cyclase (sGC) is the high affinity NO receptor in the body, and the aim of this study was to identify the precise role of sGC in acute and chronic migraine. Methods We developed a novel brain-bioavailable sGC stimulator (VL-102), and tested its hyperalgesic properties in mice...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29020807/recognizing-the-role-of-cgrp-and-cgrp-receptors-in-migraine-and-its-treatment
#9
Lars Edvinsson, Karin Warfvinge
Premise The brain and the sensory nervous system contain a rich supply of calcitonin gene-related peptide (CGRP) and CGRP receptor components. Clinical studies have demonstrated a correlation between CGRP release and acute migraine headache that led to the development of CGRP-specific drugs that either abort acute attacks of migraine (gepants) or are effective as prophylaxis (antibodies). However, there is still much discussion concerning the site of action of these drugs. Problem Here we describe the most recent data related to CGRP in the trigeminal ganglion and its connections to the CNS, putative key regions involved in migraine pathophysiology...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29019093/triptans-and-cgrp-blockade-impact-on-the-cranial-vasculature
#10
REVIEW
Silvia Benemei, Francesca Cortese, Alejandro Labastida-Ramírez, Francesca Marchese, Lanfranco Pellesi, Michele Romoli, Anne Luise Vollesen, Christian Lampl, Messoud Ashina
The trigeminovascular system plays a key role in the pathophysiology of migraine. The activation of the trigeminovascular system causes release of various neurotransmitters and neuropeptides, including serotonin and calcitonin gene-related peptide (CGRP), which modulate pain transmission and vascular tone. Thirty years after discovery of agonists for serotonin 5-HT1B and 5-HT1D receptors (triptans) and less than fifteen after the proof of concept of the gepant class of CGRP receptor antagonists, we are still a long way from understanding their precise site and mode of action in migraine...
October 10, 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28977676/pacap-receptors-in-the-trigeminovascular-system-implications-for-migraine
#11
REVIEW
Tahlia Sundrum, Christopher S Walker
The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in a wide range of functions including vasodilation, neuroprotection, nociception and neurogenic inflammation. PACAP activates three distinct receptors, the PAC1 receptor, which responds to PACAP and the VPAC1 and VPAC2 receptors, which respond to both PACAP and vasoactive intestinal polypeptide (VIP). The trigeminovascular system plays a key role in migraine and contains the trigeminal nerve, which is the major conduit of craniofacial pain...
October 4, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28972120/fremanezumab-a-humanized-monoclonal-anti-cgrp-antibody-inhibits-thinly-myelinated-a%C3%AE-but-not-unmyelinated-c-meningeal-nociceptors
#12
Agustin Melo-Carrillo, Andrew M Strassman, Rony-Reuven Nir, Aaron J Schain, Rodrigo Noseda, Jennifer Stratton, Rami Burstein
Calcitonin gene-related peptide (CGRP), the most abundant neuropeptide in primary afferent sensory neurons, is strongly implicated in the pathophysiology of migraine headache, but its role in migraine is still equivocal. As a new approach to migraine treatment, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs) were developed to reduce the availability of CGRP, and were found effective in reducing the frequency of chronic and episodic migraine. We recently tested the effect of fremanezumab (TEV-48125), a CGRP-mAb, on the activity of second-order trigeminovascular dorsal horn neurons that receive peripheral input from the cranial dura, and found a selective inhibition of high-threshold but not wide-dynamic range class of neurons...
November 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28948863/neurovascular-mechanisms-of-migraine-and-cluster-headache
#13
Jan Hoffmann, Serapio M Baca, Simon Akerman
Vascular theories of migraine and cluster headache have dominated for many years the pathobiological concept of these disorders. This view is supported by observations that trigeminal activation induces a vascular response and that several vasodilating molecules trigger acute attacks of migraine and cluster headache in susceptible individuals. Over the past 30 years, this rationale has been questioned as it became clear that the actions of some of these molecules, in particular, calcitonin gene-related peptide and pituitary adenylate cyclase-activating peptide, extend far beyond the vasoactive effects, as they possess the ability to modulate nociceptive neuronal activity in several key regions of the trigeminovascular system...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28885085/targeting-the-central-projection-of-the-dural-trigeminovascular-system-for-migraine-prophylaxis
#14
Simon Akerman, Marcela Romero-Reyes
Migraine abortives likely target both peripheral-dural and central trigeminovascular mechanisms in mediating their therapeutic effects. However, in preclinical assays, many migraine preventives have little success at inhibiting similar trigeminovascular-mediated peripheral changes within the dural microenvironment. In addition, their effects on central trigeminovascular neuronal responses are largely unknown. Using a validated preclinical model of acute dural-intracranial (migraine-like) head pain, using Sprague Dawley rats, we tested whether migraine preventives suppress ongoing firing of central trigeminocervical neurons, and evoked responses to cranial neurovascular activation...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28842814/protein-kinase-c-%C3%AE-contributes-to-central-sensitization-in-a-rat-model-of-chronic-migraine
#15
Baixue Wu, Sha Wang, Guangcheng Qin, Jingmei Xie, Ge Tan, Jiying Zhou, Lixue Chen
Protein kinase C γ (PKCγ) is a critical regulator of central sensitization and is widely recognized to be involved in the pathogenesis of chronic migraine (CM). However, the function of PKCγ in CM remains unknown. This study investigated the role of PKCγ on pathogenesis of CM. We repeated infusions of inflammatory soup (IS) on the intact dura of conscious rats to model recurrent trigeminovascular or dural nociceptor activation assumed to occur in patients with CM. The von Frey test was then used to detect changes in pain threshold...
October 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28836816/comparative-effects-of-traditional-chinese-and-western-migraine-medicines-in-an-animal-model-of-nociceptive-trigeminovascular-activation
#16
Yonglie Zhao, Margarida Martins-Oliveira, Simon Akerman, Peter J Goadsby
Background Migraine is a highly prevalent and disabling disorder of the brain with limited therapeutic options, particularly for preventive treatment. There is a need to identify novel targets and test their potential efficacy in relevant preclinical migraine models. Traditional Chinese medicines have been used for millennia and may offer avenues for exploration. Methods We evaluated two traditional Chinese medicines, gastrodin and ligustrazine, and compared them to two Western approaches with propranolol and levetiracetam, one effective and one ineffective, in an established in vivo rodent model of nociceptive durovascular trigeminal activation...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28831746/the-katp-channel-in-migraine-pathophysiology-a-novel-therapeutic-target-for-migraine
#17
Mohammad Al-Mahdi Al-Karagholi, Jakob Møller Hansen, Johanne Severinsen, Inger Jansen-Olesen, Messoud Ashina
BACKGROUND: To review the distribution and function of KATP channels, describe the use of KATP channels openers in clinical trials and make the case that these channels may play a role in headache and migraine. DISCUSSION: KATP channels are widely present in the trigeminovascular system and play an important role in the regulation of tone in cerebral and meningeal arteries. Clinical trials using synthetic KATP channel openers report headache as a prevalent-side effect in non-migraine sufferers, indicating that KATP channel opening may cause headache, possibly due to vascular mechanisms...
August 23, 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28792272/trigeminovascular-calcitonin-gene-related-peptide-function-in-cacna1a-r192q-mutated-knock-in-mice
#18
Kayi Y Chan, Alejandro Labastida-Ramírez, Martha B Ramírez-Rosas, Sieneke Labruijere, Ingrid M Garrelds, Alexander Hj Danser, Arn Mjm van den Maagdenberg, Antoinette MaassenVanDenBrink
Familial hemiplegic migraine type 1 (FHM1) is a rare migraine subtype. Whereas transgenic knock-in mice with the human pathogenic FHM1 R192Q missense mutation in the Cacna1a gene reveal overall neuronal hyperexcitability, the effects on the trigeminovascular system and calcitonin gene-related peptide (CGRP) receptor are largely unknown. This gains relevance as blockade of CGRP and its receptor are therapeutic targets under development. Hence, we set out to test these effects in FHM1 mice. We characterized the trigeminovascular system of wild-type and FHM1 mice through: (i) in vivo capsaicin- and CGRP-induced dural vasodilation in a closed-cranial window; (ii) ex vivo KCl-induced CGRP release from isolated dura mater, trigeminal ganglion and trigeminal nucleus caudalis; and (iii) peripheral vascular function in vitro ...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28776455/chronic-changes-in-pituitary-adenylate-cyclase-activating-polypeptide-and-related-receptors-in-response-to-repeated-chemical-dural-stimulation-in-rats
#19
Xun Han, Ye Ran, Min Su, Yinglu Liu, Wenjing Tang, Zhao Dong, Shengyuan Yu
Background Preclinical experimental studies revealed an acute alteration of pituitary adenylate cyclase-activating polypeptide in response to a single activation of the trigeminovascular system, which suggests a potential role of pituitary adenylate cyclase-activating polypeptide in the pathogenesis of migraine. However, changes in pituitary adenylate cyclase-activating polypeptide after repeated migraine-like attacks in chronic migraine are not clear. Therefore, the present study investigated chronic changes in pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulations in the rat...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28726232/-frequent-episodic-migraine-and-calcitonin-gene-related-peptide-influence-of-treatment-with-topiramate-and-zonisamide-on-levels-of-the-peptide
#20
D A Garcia-Estevez, M Pardo-Parrado, S Silvarrey-Rodriguez
INTRODUCTION: The pathophysiology of pain in migraine is related to the activation of the trigeminovascular system by releasing vasoactive neuropeptides, the most important of which is calcitonin gene-related peptide (CGRP), which causes a neurogenic inflammation in the leptomeningeal vessels. AIM: To study whether CGRP is increased in frequent episodic migraine and whether preventive treatment with topiramate or zonisamide modifies its levels. SUBJECTS AND METHODS: We studied 28 patients with episodic migraine with or without aura, in accordance with the International Headache Society criteria, with a frequency of 4-14 days/month...
August 16, 2017: Revista de Neurologia
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