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https://www.readbyqxmd.com/read/29022756/soluble-guanylyl-cyclase-is-a-critical-regulator-of-migraine-associated-pain
#1
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
#2
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
#3
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
#4
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
#5
Agustin Melo-Carrillo, Andrew M Strassman, Rony-Reuven Nir, Aaron 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-mAb) 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...
September 29, 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
#6
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
#7
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
#8
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...
August 25, 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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28707585/migraine-neurogenic-inflammation-drug-development-pharmacochemical-aspects
#14
Melinda Lukács, János Tajti, Ferenc Fülöp, József Toldi, Lars Edvinsson, László Vécsei
BACKGROUND: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP)...
July 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28700539/propranolol-treatment-prevents-chronic-central-sensitization-induced-by-repeated-dural-stimulation
#15
Nelly Boyer, Jérémy Signoret-Genest, Alain Artola, Radhouane Dallel, Lénaïc Monconduit
Migraine is currently conceptualized as a chronic disease with episodic manifestations. In some patients, migraine attack frequency increases, leading to chronic migraine. Daily preventive therapy is initiated to decrease attack frequency. Propranolol, a first-line medication for migraine prophylaxis, reduces attack frequency in nearly 50% of patients receiving it. However, the mechanisms of its antimigraine action are unclear. We examined the effect of daily propranolol treatment (10 mg·kg per os, 8 days) in a rat model of recurrent activation of dural nociceptors (repeated infusion of an inflammatory soup (IS) on the dura through a cannula every 2-3 days)...
July 8, 2017: Pain
https://www.readbyqxmd.com/read/28699403/rna-seq-investigations-of-human-post-mortem-trigeminal-ganglia
#16
Danielle M LaPaglia, Matthew R Sapio, Peter D Burbelo, Jean Thierry-Mieg, Danielle Thierry-Mieg, Stephen J Raithel, Christopher E Ramsden, Michael J Iadarola, Andrew J Mannes
Background The trigeminal ganglion contains neurons that relay sensations of pain, touch, pressure, and many other somatosensory modalities to the central nervous system. The ganglion is also a reservoir for latent herpes virus 1 infection. To gain a better understanding of molecular factors contributing to migraine and headache, transcriptome analyses were performed on postmortem human trigeminal ganglia. Methods RNA-Seq measurements of gene expression were conducted on small sub-regions of 16 human trigeminal ganglia...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28642283/selective-inhibition-of-trigeminovascular-neurons-by-fremanezumab-a-humanized-monoclonal-anti-cgrp-antibody
#17
Agustin Melo-Carrillo, Rodrigo Noseda, Rony Nir, Aaron J Schain, Jennifer Stratton, Andrew M Strassman, Rami Burstein
A large body of evidence supports an important role for calcitonin gene-related peptide (CGRP) in migraine pathophysiology. This evidence gave rise to a global effort to develop a new generation of therapeutics that inhibit the interaction of CGRP with its receptor in migraineurs. Recently, a new class of such drugs, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs), were found to be effective in reducing the frequency of migraine. The purpose of this study was to better understand how the CGRP-mAb fremanezumab (TEV-48125) modulates meningeal sensory pathways...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28616038/electroacupuncture-at-fengchi-gb20-inhibits-calcitonin-gene-related-peptide-expression-in-the-trigeminovascular-system-of-a-rat-model-of-migraine
#18
Luo-Peng Zhao, Lu Liu, Pei Pei, Zheng-Yang Qu, Yu-Pu Zhu, Lin-Peng Wang
Most migraine patients suffer from cutaneous allodynia; however, the underlying mechanisms are unclear. Calcitonin gene-related peptide (CGRP) plays an important role in the pathophysiology of migraine, and it is therefore, a potential therapeutic target for treating the pain. In the present study, a rat model of conscious migraine, induced by repeated electrical stimulation of the superior sagittal sinus, was established and treated with electroacupuncture at Fengchi (GB20) (depth of 2-3 mm, frequency of 2/15 Hz, intensity of 0...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28580293/acupuncture-modulates-the-abnormal-brainstem-activity-in-migraine-without-aura-patients
#19
Zhengjie Li, Fang Zeng, Tao Yin, Lei Lan, Nikos Makris, Kristen Jorgenson, Taipin Guo, Feng Wu, Yujie Gao, Mingkai Dong, Mailan Liu, Jie Yang, Ying Li, Qiyong Gong, Fanrong Liang, Jian Kong
Migraine is a common neurological disease with a high prevalence and unsatisfactory treatment options. The specific pathophysiological mechanisms of migraine remain unclear, which restricts the development of effective treatments for this prevalent disorder. The aims of this study were to 1) compare the spontaneous brain activity differences between Migraine without Aura (MwoA) patients and healthy controls (HCs), using amplitude of low-frequency fluctuations (ALFF) calculation method, and 2) explore how an effective treatment (verum acupuncture) could modulate the ALFF of MwoA patients...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28542895/aura-and-other-neurologic-dysfunction-in-or-with-migraine
#20
Narayan R Kissoon, Fred Michael Cutrer
PREMISE: Migraine can present with a wide range of neurological symptoms. PROBLEM: Based on currently available data, the symptoms of typical migraine aura are most likely related to cortical spreading depression (CSD), and evidence supports that CSD can lead to trigeminovascular activation resulting in the headache phase of migraine. POTENTIAL SOLUTION: An alternative diagnosis to migraine aura should be considered if migrainous headaches present with transient neurological symptoms that have features inconsistent with aura...
July 2017: Headache
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