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https://www.readbyqxmd.com/read/28642283/selective-inhibition-of-trigeminovascular-neurons-by-fremanezumab-a-humanized-monoclonal-anti-cgrp-antibody
#1
Agustin Melo-Carrillo, Rodrigo Noseda, Rony Nir, Aaron Schain, Jennifer Stratton, Andrew M Strassman, Rami Burstein
A large body of evidence supports an important role for 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 monoclonal anti-CGRP antibodies (CGRP-mAb) 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...
June 22, 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
#2
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
#3
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
#4
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...
May 19, 2017: Headache
https://www.readbyqxmd.com/read/28488307/baicalin-alleviates-nitroglycerin-induced-migraine-in-rats-via-the-trigeminovascular-system
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
(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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28108291/neuroendocrine-signaling-modulates-specific-neural-networks-relevant-to-migraine
#15
Margarida Martins-Oliveira, Simon Akerman, Philip R Holland, Jan R Hoffmann, Isaura Tavares, Peter J Goadsby
Migraine is a disabling brain disorder involving abnormal trigeminovascular activation and sensitization. Fasting or skipping meals is considered a migraine trigger and altered fasting glucose and insulin levels have been observed in migraineurs. Therefore peptides involved in appetite and glucose regulation including insulin, glucagon and leptin could potentially influence migraine neurobiology. We aimed to determine the effect of insulin (10U·kg(-1)), glucagon (100μg·200μl(-1)) and leptin (0.3, 1 and 3mg·kg(-1)) signaling on trigeminovascular nociceptive processing at the level of the trigeminocervical-complex and hypothalamus...
May 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/27919795/current-and-novel-insights-into-the-neurophysiology-of-migraine-and-its-implications-for-therapeutics
#16
REVIEW
Simon Akerman, Marcela Romero-Reyes, Philip R Holland
Migraine headache and its associated symptoms have plagued humans for two millennia. It is manifest throughout the world, and affects more than 1/6 of the global population. It is the most common brain disorder, and is characterized by moderate to severe unilateral headache that is accompanied by vomiting, nausea, photophobia, phonophobia, and other hypersensitive symptoms of the senses. While there is still a clear lack of understanding of its neurophysiology, it is beginning to be understood, and it seems to suggest migraine is a disorder of brain sensory processing, characterized by a generalized neuronal hyperexcitability...
April 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27898338/effect-of-pgd2-on-middle-meningeal-artery-and-mrna-expression-profile-of-l-pgd2-synthase-and-dp-receptors-in-trigeminovascular-system-and-other-pain-processing-structures-in-rat-brain
#17
Aysegül Sekeroglu, Julie Mie Jacobsen, Inger Jansen-Olesen, Saurabh Gupta, Majid Sheykhzade, Jes Olesen, Deepak K Bhatt
BACKGROUND: Prostaglandins (PGs), particularly prostaglandin D2 (PGD2), E2 (PGE2), and I2 (PGI2), are considered to play a role in migraine pain. In humans, infusion of PGD2 causes lesser headache as compared to infusion of PGE2 and PGI2. Follow-up studies in rats have shown that infusion of PGE2 and PGI2 dilate the middle meningeal artery (MMA), and mRNA for PGE2 and PGI2 receptors is present in rat trigeminovascular system (TVS) and in the brain structures associated with pain. In the present study, we have characterized the dilatory effect of PGD2 on rat MMA and studied the relative mRNA expression of PGD2 receptors and lipocalin-type of PGD2 synthase (L-PGDS)...
February 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27819404/-calcitonin-gene-related-peptide-a-key-player-neuropeptide-in-migraine
#18
REVIEW
M L Ramos-Romero, F E Sobrino-Mejia
Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP is widely distributed in the nervous system, particularly at anatomical areas thought to be involved with migraine pathophysiology, including the trigeminovascular nociceptive system. Over the past two decades, a convergence of basic and clinical evidence has established the CGRP as a key player in migraine. CGRP enhances sensitivity to sensory input at multiple levels in both the periphery and central nervous system...
November 16, 2016: Revista de Neurologia
https://www.readbyqxmd.com/read/27778243/activation-of-the-nuclear-factor-e2-related-factor%C3%A2-2-anitioxidant-response-element-alleviates-the-nitroglycerin-induced-hyperalgesia-in-rats
#19
Wei Di, Xiaolei Shi, Hua Lv, Jun Liu, Hong Zhang, Zhiwei Li, Yannan Fang
BACKGROUND: Antioxidants have been proven to weaken hyperalgesia in neuropathic pain. Endogenous antioxidant defense system may have a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in regulating the activation of the trigeminovascular system (TGVS) and hypersensitivity in nitroglycerin (NTG)-induced hyperalgesia rats. METHODS: The expression levels of Nrf2, HO, HO1, and NQO1 in the trigeminal nucleus caudalis (TNC) were detected by western blot...
December 2016: Journal of Headache and Pain
https://www.readbyqxmd.com/read/27770405/pharmacology-of-reflex-blinks-in-the-rat-a-novel-model-for-headache-research
#20
M G Jones, A P Andreou, S B McMahon, D Spanswick
BACKGROUND: Migraineurs are highly sensitive to the nitric oxide donor glyceryl trinitrate which triggers attacks in many sufferers. In animal studies, glyceryl trinitrate increases neuronal activity in the trigeminovascular pathway and elevates neurotransmitter levels in the brainstem. Many migraineurs also display alterations in blink reflexes, known to involve brainstem circuits. We investigated the effect of GTN on evoked blinks in the anaesthetised rat to determine whether such reflexes may prove useful as the basis for a novel animal model to evaluate potential anti-migraine therapeutic agents...
December 2016: Journal of Headache and Pain
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