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https://www.readbyqxmd.com/read/27919795/current-and-novel-insights-into-the-neurophysiology-of-migraine-and-its-implications-for-therapeutics
#1
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...
December 2, 2016: 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
#2
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)...
September 19, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27819404/-calcitonin-gene-related-peptide-a-key-player-neuropeptide-in-migraine
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/27707951/different-processing-of-meningeal-and-cutaneous-pain-information-in-the-spinal-trigeminal-nucleus-caudalis
#6
Céline Melin, Florian Jacquot, Nicolas Vitello, Radhouane Dallel, Alain Artola
INTRODUCTION: Within superficial trigeminal nucleus caudalis (Sp5C) (laminae I/II), meningeal primary afferents project exclusively to lamina I, whereas nociceptive cutaneous ones distribute in both lamina I and outer lamina II. Whether such a relative absence of meningeal inputs to lamina II represents a fundamental difference from cutaneous pathways in the central processing of sensory information is still unknown. METHODS: We recorded extracellular field potentials in the superficial Sp5C of anesthetised rats evoked by electrically stimulating the dura mater, to selectively assess the synaptic transmission between meningeal primary afferents and second-order Sp5C neurons, the first synapse in trigeminovascular pathways...
October 5, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27677650/inhibitory-effect-of-high-frequency-greater-occipital-nerve-electrical-stimulation-on-trigeminovascular-nociceptive-processing-in-rats
#7
Olga A Lyubashina, Sergey S Panteleev, Alexey Y Sokolov
Electrical stimulation of the greater occipital nerve (GON) has recently shown promise as an effective non-pharmacological prophylactic therapy for drug-resistant chronic primary headaches, but the neurobiological mechanisms underlying its anticephalgic action are not elucidated. Considering that the spinal trigeminal nucleus (STN) is a key segmental structure playing a prominent role in pathophysiology of headaches, in the present study we evaluated the effects of GON electrical stimulation on ongoing and evoked firing of the dura-sensitive STN neurons...
September 27, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27642579/current-understanding-on-pain-mechanism-in-migraine-and-cluster-headache
#8
REVIEW
Alina Buture, Rubesh Gooriah, Randa Nimeri, Fayyaz Ahmed
CONTEXT: Migraine and cluster headache are undoubtedly painful conditions. The respective pathogenesis of these two conditions is incompletely understood. In both cases, the treatments used have largely been empirical and have relied to a much lesser extent on our understanding of the mechanisms causing pain. We hereby review the pain mechanisms in migraine and cluster headache, two of the commonest primary headache disorders. EVIDENCE ACQUISITION: A review of the English literature was conducted by searching PubMed for studies on pain mechanism in migraine and cluster headache...
June 2016: Anesthesiology and Pain Medicine
https://www.readbyqxmd.com/read/27618395/valproate-attenuates-nitroglycerin-induced-trigeminovascular-activation-by-preserving-mitochondrial-function-in-a-rat-model-of-migraine
#9
Ruxian Li, Yushuang Liu, Nan Chen, Yitong Zhang, Ge Song, Zhongling Zhang
BACKGROUND Migraine is a chronic disease that interferes with life quality and work productivity. Valproate shows protective effects against migraine, yet the underlying mechanisms are unclear. This study aimed to evaluate the potential effect of valproate on migraine using a rat model of nitroglycerin-induced trigeminovascular activation, as well as to explore the underlying mechanism. MATERIAL AND METHODS Intraperitoneal injection of nitroglycerin was conducted to induce trigeminovascular activation in rats...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27606340/metabotropic-glutamate-receptor-5-a-target-for-migraine-therapy
#10
Maggie W Waung, Simon Akerman, Mark Wakefield, Charlotte Keywood, Peter J Goadsby
INTRODUCTION: Many patients suffering from migraine gain little relief from existing treatments partly because many existing acute and preventive therapies used in migraine have been adopted from other neurologic conditions such as depression or epilepsy. Here, we present data supporting a new migraine-specific target, the mGlu5 receptor. METHODS: We studied the effect of mGlu5 blockade using ADX10059, on neuronal firing in the trigeminocervical complex (TCC) and durovascular effects of nociceptive trigeminovascular activation in the anesthetized rat...
August 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/27553188/targeting-of-calcitonin-gene-related-peptide-action-as-a-new-strategy-for-migraine-treatment
#11
Olga Kuzawińska, Krzysztof Lis, Grzegorz Cessak, Dagmara Mirowska-Guzel, Ewa Bałkowiec-Iskra
Migraine is a chronic, recurrent disorder, characterized by attacks of severe pain, affecting around 1% of adult population. Many studies suggest, that trigeminovascular system plays a key role in pathogenesis of migraine and other primary headaches. Calcitonin gene-related peptide (CGRP) is an endogenous substance, which is regarded a key mediator released from trigeminovascular system after stimulation of sensory nerve endings, responsible for dilatation of peripheral vessels and sensory transmission. CGRP is and extensively studied peptide as one of the most promising targets in migraine drug research...
August 10, 2016: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/27522962/monosodium-glutamate-alters-the-response-properties-of-rat-trigeminovascular-neurons-through-activation-of-peripheral-nmda-receptors
#12
Melissa O'Brien, Brian E Cairns
Ingestion of monosodium glutamate (MSG) has been shown to cause headaches in healthy individuals and trigger migraine-like headaches in migraine sufferers. We combined immunohistochemistry, in vivo electrophysiology, and laser Doppler recordings of dural vasculature to investigate the effect of systemic administration of MSG on the trigeminovascular pathway. Immunohistochemical analysis confirmed the expression of NMDA receptors on nerve fibres innervating dural blood vessels and excitatory amino acid transporter 2 on dural blood vessels...
August 11, 2016: Neuroscience
https://www.readbyqxmd.com/read/27465216/the-role-of-5-hydroxytryptamine-in-the-pathophysiology-of-migraine-and-its-relevance-to-the-design-of-novel-treatments
#13
Carlos M Villalón, Antoinette Maassen VanDenBrink
Migraine is a highly prevalent neurovascular disorder. Of the many factors that have been implicated over the years, 5-hydroxytryptamine (5-HT; serotonin) has long been involved in the pathophysiology of migraine. Certainly, some lines of evidence suggest: (i) a 5-HT depletion from blood platelets resulting in cranial extracerebral vasodilatation; and (ii) the effectiveness of an intravenous (i.v.) infusion of 5 HT to abort migraine in some patients. More direct evidence comes from some drugs that influence 5-HT release and/or interact (as agonists or antagonists) with 5-HT receptors to treat this disorder...
July 28, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27338837/wiping-out-cgrp-potential-cardiovascular-risks
#14
REVIEW
Antoinette MaassenVanDenBrink, Joris Meijer, Carlos M Villalón, Michel D Ferrari
Migraine is a common episodic neurovascular brain disorder associated with increased risk of cardio- and cerebrovascular ischemia. Migraine headache is likely caused by activation of the trigeminovascular system and release of calcitonin gene-related peptide (CGRP). Monoclonal antibodies against CGRP or its receptor are currently being evaluated for the prevention of migraine attacks. Preliminary efficacy data are promising. However, because CGRP may act as a vasodilatory safeguard during cerebral and cardiac ischemia, CGRP blockade could transform transient mild ischemic events into full-blown infarcts...
September 2016: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/27301459/diet-induced-obesity-alters-dural-cgrp-release-and-potentiates-trpa1-mediated-trigeminovascular-responses
#15
Balázs Marics, Barna Peitl, Angelika Varga, Kitti Pázmándi, Attila Bácsi, József Németh, Zoltán Szilvássy, Gábor Jancsó, Mária Dux
BACKGROUND: Clinical studies suggest a link between obesity and the primary headache disorder migraine. In our study we aimed to reveal the effect of obesity on meningeal nociceptor function in rats receiving a high-fat, high-sucrose diet. METHODS: Transient receptor potential ankyrin 1 (TRPA1) receptor activation-induced changes in meningeal blood flow, release of calcitonin gene-related peptide (CGRP) from trigeminal afferents and TRPA1 protein expression in the trigeminal ganglia were measured in control and obese rats...
June 14, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27293545/pituitary-adenylate-cyclase-activating-polypeptide-expression-in-peripheral-blood-mononuclear-cells-of-migraineurs
#16
Lei Hou, Dongjun Wan, Zhao Dong, Wenjing Tang, Xun Han, Li Li, Fei Yang, Shengyuan Yu
BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) plays several important roles in vasodilation, neurotransmission, neuromodulation and neurotrophy, as well as activation of the trigeminovascular system. The aim of the present study was to explore the relationship between altered PACAP levels in peripheral blood and different types of headache. METHODS: The present study enrolled 101 outpatients with headache and 35 healthy control volunteers...
2016: Cell & Bioscience
https://www.readbyqxmd.com/read/27246325/transcranial-magnetic-stimulation-and-potential-cortical-and-trigeminothalamic-mechanisms-in-migraine
#17
Anna P Andreou, Philip R Holland, Simon Akerman, Oliver Summ, Joe Fredrick, Peter J Goadsby
A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats...
July 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27215627/spreading-depression-in-primary-and-secondary-headache-disorders
#18
REVIEW
Shih-Pin Chen, Cenk Ayata
PURPOSE OF REVIEW: Spreading depression (SD) is a wave of simultaneous and near-complete depolarization of virtually all cells in brain tissue associated with a transient "depression" of all spontaneous or evoked electrical activity in the brain. SD is widely accepted as the pathophysiological event underlying migraine aura and may play a role in headache pathogenesis in secondary headache disorders such as ischemic stroke, subarachnoid or intracerebral hemorrhage, traumatic brain injury, and epilepsy...
July 2016: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/27189587/endovanilloids-are-potential-activators-of-the-trigeminovascular-nocisensor-complex
#19
Mária Dux, Éva Deák, Noémi Tassi, Péter Sántha, Gábor Jancsó
BACKGROUND: In the dura mater encephali a significant population of trigeminal afferents coexpress the nociceptive ion channel transient receptor potential vanilloid type 1 (TRPV1) receptor and calcitonin gene-related peptide (CGRP). Release of CGRP serves the central transmission of sensory information, initiates local tissue reactions and may also sensitize the nociceptive pathway. To reveal the possible activation of meningeal TRPV1 receptors by endogenously synthetized agonists, the effects of arachidonylethanolamide (anandamide) and N-arachidonoyl-dopamine (NADA) were studied on dural vascular reactions and meningeal CGRP release...
2016: Journal of Headache and Pain
https://www.readbyqxmd.com/read/27155150/immunohistochemical-localization-of-the-calcitonin-gene-related-peptide-binding-site-in-the-primate-trigeminovascular-system-using-functional-antagonist-antibodies
#20
Silke Miller, Hantao Liu, Karin Warfvinge, Licheng Shi, Mary Dovlatyan, Cen Xu, Lars Edvinsson
Calcitonin gene-related peptide (CGRP) is a potent vasodilator and a neuromodulator implicated in the pathophysiology of migraine. It binds to the extracellular domains of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein (RAMP) 1 that together form the CGRP receptor. Antagonist antibodies against CGRP and its binding site at the receptor are clinically effective in preventing migraine attacks. The blood-brain barrier penetration of these antagonist antibodies is limited, suggesting that a potential peripheral site of action is sufficient to prevent migraine attacks...
July 22, 2016: Neuroscience
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