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https://www.readbyqxmd.com/read/29438129/central-and-peripheral-processes-in-headache
#1
Adithya Varma, Saurabh Jain, Arshad Majid, Milena De Felice
PURPOSE OF REVIEW: Migraine is an extremely incapacitating collection of neurological symptoms that usually includes a severe, throbbing, recurring pain on one side of the head. The World Health Organization ranks migraine as the third most prevalent disease and the seventh commonest primary pain condition in the world. Trigeminovascular-mediated central sensitization has been implicated in the development of migraine symptoms including pain following light touch. This review explores the activation and sensitization of the brain systems that have emerged from recent studies and that contribute to migraine...
February 12, 2018: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/29357683/cerebellar-involvement-in-migraine
#2
Lieke Kros, Chantal A Angueyra Aristizábal, Kamran Khodakhah
Background Although there is a great wealth of knowledge about the neurobiological processes underlying migraine and its accompanying symptoms, the mechanisms by which an attack starts remain elusive, and the disease remains undertreated. Although the vast majority of literature focuses on the involvement of the trigeminovascular systems and higher systems it innervates, such as thalamic and hypothalamic nuclei, several lines of evidence implicate the cerebellum in the pathophysiology of migraine. Aim In this review, we aim to summarize potential cerebellar involvement seen from different perspectives including the results from imaging studies, cerebellar connectivity to migraine-related brain structures, comorbidity with disorders implying cerebellar dysfunction, similarities in triggers precipitating both such disorders, and migraine and cerebellar expression of migraine-related genes and neuropeptides...
January 1, 2018: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29352859/is-selective-5-ht1f-receptor-agonism-an-entity-apart-from-that-of-the-triptans-in-antimigraine-therapy
#3
REVIEW
Eloísa Rubio-Beltrán, Alejandro Labastida-Ramírez, Carlos M Villalón, Antoinette MaassenVanDenBrink
Migraine is a neurovascular disorder that involves activation of the trigeminovascular system and cranial vasodilation mediated by release of calcitonin gene-related peptide (CGRP). The gold standard for acute migraine treatment are the triptans, 5-HT1B/1D/(1F) receptor agonists. Their actions are thought to be mediated through activation of: (i) 5-HT1B receptors in cranial blood vessels with subsequent cranial vasoconstriction; (ii) prejunctional 5-HT1D receptors on trigeminal fibers that inhibit trigeminal CGRP release; and (iii) 5-HT1B/1D/1F receptors in central nervous system involved in (anti)nociceptive modulation...
January 17, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29317063/trigeminal-long-term-potentiation-as-a-cellular-substrate-for-migraine
#4
Dong-Ho Youn
Most previous studies suggest that the subnucleus caudalis (Vc) of spinal trigeminal nucleus (Vsp) plays a key role in the generation and maintenance of migraine, a type of primary headache, by participating in the trigeminovascular system. Furthermore, the excitability of the Vc with the stimulation of the peripheral nociceptive fibers innervating the intracranial vessels or dura matter is regarded as a main cellular substrate for migraine. Here, a revised hypothesis is introduced, reinforcing the previous hypothesis and complementing it...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29260608/tonic-regulation-of-middle-meningeal-artery-diameter-by-atp-sensitive-potassium-channels
#5
Arsalan U Syed, Masayo Koide, Joseph E Brayden, George C Wellman
Activation of ATP-sensitive potassium (KATP) channels in arterial smooth muscle (ASM) contributes to vasodilation evoked by a variety of endogenous and exogenous compounds. Although controversial, activation of KATP channels by neuropeptides such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating peptide (PACAP) in the trigeminovascular system, including the middle meningeal artery (MMA), has been linked to migraine headache. The objective of the current study was to determine if ongoing KATP channel activity also influences MMA diameter...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29237283/ghrelin-attenuated-hyperalgesia-induced-by-chronic-nitroglycerin-cgrp-and-trpv1-as-targets-for-migraine-management
#6
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
#7
REVIEW
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...
January 2018: 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
#8
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
#9
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
#10
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
#11
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
#12
REVIEW
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...
December 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29022756/soluble-guanylyl-cyclase-is-a-critical-regulator-of-migraine-associated-pain
#13
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
#14
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
#15
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/pituitary-adenylate-cyclase-activating-polypeptide-receptors-in-the-trigeminovascular-system-implications-for-migraine
#16
REVIEW
Tahlia Sundrum, Christopher S Walker
The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in a wide range of functions including vasodilatation, 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. 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
#17
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
#18
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
#19
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
#20
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
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