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https://www.readbyqxmd.com/read/28792272/trigeminovascular-calcitonin-gene-related-peptide-function-in-cacna1a-r192q-mutated-knock-in-mice
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28488307/baicalin-alleviates-nitroglycerin-induced-migraine-in-rats-via-the-trigeminovascular-system
#11
Yu-Yao Sun, Wen-Jun Zhang, Cui-Lan Dong, Xiao-Fan Zhang, Jun Ji, Xue Wang, Ling Wang, Wan-Li Hu, Wen-Juan Du, Cheng-Long Cui, Chun-Feng Zhang, Fei Li, Chong-Zhi Wang, Chun-Su Yuan
Migraine is a common neurological disorder with a serious impact on quality of life. The aim of this study was to explore the effect of baicalin on nitroglycerin-induced migraine rats. We carried out a behavioral research within 2 h post-nitroglycerin injection, and blood samples were drawn for measurements of nitric oxide (NO), calcitonin gene-related peptide, and endothelin (ET) levels. Immunohistochemistry was adopted to detect the activation of C-fos immunoreactive neurons in periaqueductal gray. The number, area size, and integrated optical density of C-fos positive cells were measured using Image-Pro Plus...
June 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28485848/the-trigeminovascular-pathway-role-of-cgrp-and-cgrp-receptors-in-migraine
#12
REVIEW
Lars Edvinsson
The trigeminal ganglion plays a key role in primary headache pathophysiology. Calcitonin gene-related peptide (CGRP) and CGRP receptors are expressed in trigeminal neurons that form C-fibers and A-fibers, respectively. In acute migraine and cluster headache attacks, there is release of CGRP into the cranial venous outflow. In addition, intravenous CGRP can induce migraine-like symptoms in migraine patients. These findings led to the development of anti-migraine therapies that inhibit CGRP action. Currently, CGRP receptor antagonists, the gepants, and monoclonal antibodies towards CGRP and the CGRP receptor are all showing positive relief of acute and chronic migraine in clinical trials...
May 2017: Headache
https://www.readbyqxmd.com/read/28485844/neuropeptides-and-neurotransmitters-that-modulate-thalamo-cortical-pathways-relevant-to-migraine-headache
#13
REVIEW
Rodrigo Noseda, David Borsook, Rami Burstein
Dynamic thalamic regulation of sensory signals allows the cortex to adjust better to rapidly changing behavioral, physiological, and environmental demands. To fulfill this role, thalamic neurons must themselves be subjected to constantly changing modulatory inputs that originate in multiple neurochemical pathways involved in autonomic, affective, and cognitive functions. This review defines a chemical framework for thinking about the complexity of factors that modulate the response properties of relay trigeminovascular thalamic neurons...
May 2017: Headache
https://www.readbyqxmd.com/read/28478842/periodontal-disease-as-a-potential-factor-of-migraine-chronification
#14
Pablo Ameijeira, Yago Leira, Juan Blanco, Rogelio Leira
Migraine is a hereditary constitutional base disorder, which is characterized by recurrent episodes of headache pulsatile characteristics associated with photophobia/phonophobia, nausea and/or vomiting. The main complication in migraine is the chronicity of the process, now recognized as a chronic migraine. Although pathogenic mechanisms that may influence the pathophysiology of migraine and its possible chronicity are not fully understood, previous studies have shown in patients with migraine molecular alterations of systemic inflammation, neurogenic inflammation, endothelial dysfunction, innate immunity, dysfunction of matrix proteases and blood-brain barrier...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28430869/inhibition-of-the-p2x7-panx1-complex-suppresses-spreading-depolarization-and-neuroinflammation
#15
Shih-Pin Chen, Tao Qin, Jessica L Seidel, Yi Zheng, Matthias Eikermann, Michel D Ferrari, Arn M J M van den Maagdenberg, Michael A Moskowitz, Cenk Ayata, Katharina Eikermann-Haerter
Spreading depolarization is a wave of neuronal and glial depolarization. Within minutes after spreading depolarization, the neuronal hemichannel pannexin 1 (PANX1) opens and forms a pore complex with the ligand-gated cation channel P2X7, allowing the release of excitatory neurotransmitters to sustain spreading depolarization and activate neuroinflammation. Here, we explore the hypothesis that the P2X7-PANX1 pore complex is a critical determinant of spreading depolarization susceptibility with important consequences for neuroinflammation and trigeminovascular activation...
June 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28337634/topical-dura-mater-application-of-cfa-induces-enhanced-expression-of-c-fos-and-glutamate-in-rat-trigeminal-nucleus-caudalis-attenuated-by-kyna-derivate-szr72
#16
M Lukács, K Warfvinge, J Tajti, F Fülöp, J Toldi, L Vécsei, L Edvinsson
BACKGROUND: Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund's Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72...
December 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28301861/neuropeptide-y-inhibits-the-trigeminovascular-pathway-through-npy-y1-receptor-implications-for-migraine-erratum
#17
(no author information available yet)
No abstract text is available yet for this article.
April 2017: Pain
https://www.readbyqxmd.com/read/28245765/kynurenines-and-pacap-in-migraine-medicinal-chemistry-and-pathogenetic-aspects
#18
János Tajti, Délia Szok, Gábor Nagy-Grócz, Bernadett Tuka, Anna Petrovics-Balog, József Toldi, László Vécsei
BACKGROUND: Migraine is a highly disabling neurovascular primary headache disorder, with its exact pathomechanism being still unrevealed. The current leading hypotheses are based on the sensitization and activation of the trigeminovascular system. OBJECTIVE: To review the literature with focus on the effects of kynurenines (L-kynurenine and kynurenic acid) and pituitary adenylate cyclase-activating polypeptide on the regulation of the trigeminovascular system. METHOD: A literature search was conducted to identify preclinical and clinical publications (198 references) by using the keywords 'kynurenines', 'pituitary adenylate cyclase-activating polypeptide', and 'migraine' in the database of MEDLINE/PubMed up to 10 September 2016for topical review...
February 27, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28165287/cgrp-receptor-antagonist-activity-of-olcegepant-depends-on-the-signalling-pathway-measured
#19
Christopher S Walker, Ann C Raddant, Michael J Woolley, Andrew F Russo, Debbie L Hay
Background Calcitonin gene-related peptide (CGRP) is a neuropeptide that acts in the trigeminovascular system and is believed to play an important role in migraine. CGRP activates two receptors that are both present in the trigeminovascular system; the CGRP receptor and the amylin 1 (AMY1) receptor. CGRP receptor antagonists, including olcegepant (BIBN4096BS) and telcagepant (MK-0974), can treat migraine. This study aimed to determine the effectiveness of these antagonists at blocking CGRP receptor signalling in trigeminal ganglia (TG) neurons and transfected CGRP and AMY1 receptors in Cos7 cells, to better understand their mechanism of action...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28133727/diet-induced-obesity-enhances-trpv1-mediated-neurovascular-reactions-in-the-dura-mater
#20
Balázs Marics, Barna Peitl, Kitti Pázmándi, Attila Bácsi, József Németh, Orsolya Oszlács, Gábor Jancsó, Mária Dux
OBJECTIVE: Exploring the pathophysiological changes in transient receptor potential vanilloid 1 (TRPV1) receptor of the trigeminovascular system in high-fat, high-sucrose (HFHS) diet-induced obesity of experimental animals. BACKGROUND: Clinical and experimental observations suggest a link between obesity and migraine. Accumulating evidence indicates that metabolic and immunological alterations associated with obesity may potentially modulate trigeminovascular functions...
March 2017: Headache
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