scholarly journals Neurovascular mechanisms of migraine and cluster headache

2017 ◽  
Vol 39 (4) ◽  
pp. 573-594 ◽  
Author(s):  
Jan Hoffmann ◽  
Serapio M Baca ◽  
Simon Akerman
Keyword(s):  
Cluster Headache ◽  
Vascular Response ◽  
Trigeminovascular System ◽  
The Past ◽  
Anatomical Basis ◽  
Calcitonin Gene ◽  
Pituitary Adenylate Cyclase ◽  
Acute Attacks ◽  
Trigeminal Activation

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. These findings have shifted our understanding of these disorders to a primarily neuronal origin with the vascular manifestations being the consequence rather than the origin of trigeminal activation. Nevertheless, the neurovascular component, or coupling, seems to be far more complex than initially thought, being involved in several accompanying features. The review will discuss in detail the anatomical basis and the functional role of the neurovascular mechanisms relevant to migraine and cluster headache.

Recognizing the role of CGRP and CGRP receptors in migraine and its treatment

Cephalalgia ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 366-373 ◽  
Author(s):  
Lars Edvinsson ◽  
Karin Warfvinge
Keyword(s):  
Small Molecules ◽  
Migraine Headache ◽  
The Novel ◽  
Trigeminovascular System ◽  
Calcitonin Gene ◽  
Site Of Action ◽  
Acute Attacks ◽  
Sensory Nervous System ◽  
The Brain

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. Gepants are small molecules that have limited ability to cross the blood-brain barrier (BBB), whereas CGRP antibodies are 1500 times larger molecules, and are virtually excluded from the brain, with a BBB permeability of < 0.1%. Thus we propose that the primary site of action for the antimigraine drugs is outside the CNS in areas not limited by the BBB. Potential solution Therefore, it is reasonable to discuss the localization of CGRP and its receptor components in relation to the BBB. The trigeminovascular system, located outside the BBB, has a key role in migraine symptomatology, and it is likely targeted by the novel CGRP drugs that successfully terminate migraine headache.

scholarly journals Role Of Cgrp In Sensitization Of Dura Mater

2001 ◽  
Vol 1 ◽  
pp. 20-20
Author(s):  
K. Messlinger
Keyword(s):  
Dura Mater ◽  
Trigeminal Nerve ◽  
Plasma Levels ◽  
Nerve Fibers ◽  
Considerable Proportion ◽  
Trigeminovascular System ◽  
Dura Mater Encephali ◽  
Related Peptide ◽  
Calcitonin Gene

The mammalian dura mater encephali is richly supplied by trigeminal nerve fibers, a considerable proportion of which contains calcitonin gene-related peptide (CGRP). As plasma levels of CGRP are increased in some forms of headaches, the question is in which way CGRP is involved in nociceptive mechanisms within the peripheral and the central trigeminovascular system.

scholarly journals Alterations in PACAP-38-like immunoreactivity in the plasma during ictal and interictal periods of migraine patients

Cephalalgia ◽  
2013 ◽  
Vol 33 (13) ◽  
pp. 1085-1095 ◽  
Author(s):  
Bernadett Tuka ◽  
Zsuzsanna Helyes ◽  
Adrienn Markovics ◽  
Teréz Bagoly ◽  
János Szolcsányi ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Healthy Subjects ◽  
Disease Duration ◽  
Animal Experiments ◽  
Control Group ◽  
Trigeminovascular System ◽  
Blood Samples ◽  
Calcitonin Gene ◽  
Pituitary Adenylate Cyclase ◽  
Healthy Control

Background Recent studies on migraineurs and our own animal experiments have revealed that pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) has an important role in activation of the trigeminovascular system. The aim of this study was to determine the PACAP-38-like immunoreactivity (LI) in the plasma of healthy subjects, and parallel with the calcitonin gene-related peptide (CGRP)-LI in migraine patients in the ictal and interictal periods. Methods A total of 87 migraineurs and 40 healthy control volunteers were enrolled in the examination. Blood samples were collected from the cubital veins in both periods in 21 patients, and in either the ictal or the interictal period in the remaining 66 patients, and were analysed by radioimmunoassay. Results A significantly lower PACAP-38-LI was measured in the interictal plasma of the migraineurs as compared with the healthy control group ( p < 0.011). In contrast, elevated peptide levels were detected in the ictal period relative to the attack-free period in the 21 migraineurs ( pPACAP-38 < 0.001; pCGRP < 0.035) and PACAP-38-LI in the overall population of migraineurs ( p < 0.009). A negative correlation was observed between the interictal PACAP-38-LI and the disease duration. Conclusion This is the first study that has provided evidence of a clear association between migraine phases (ictal and interictal) and plasma PACAP-38-LI alterations.

Corticosteroids alter CGRP and melatonin release in cluster headache episodes

Cephalalgia ◽  
2014 ◽  
Vol 35 (4) ◽  
pp. 317-326 ◽  
Author(s):  
Lars Neeb ◽  
Linn Anders ◽  
Philipp Euskirchen ◽  
Jan Hoffmann ◽  
Heike Israel ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Plasma Levels ◽  
External Jugular Vein ◽  
Short Term ◽  
Hypothalamic Dysfunction ◽  
Calcitonin Gene ◽  
Observational Cohort ◽  
Trigeminal Activation ◽  
Melatonin Production ◽  
Urine Levels

Background Calcitonin gene-related peptide (CGRP) is a marker of trigeminal activation in acute cluster headache (CH). Melatonin production is altered in CH patients and may reflect hypothalamic dysfunction. We assessed the effects of short-term CH prevention with corticosteroids on CGRP and melatonin release in a prospective observational cohort study hypothesizing that corticosteroids influence the interictal activity of both systems indicated by the change of these biomarkers. Methods Episodic CH subjects ( n = 9) in the bout and controls with multiple sclerosis ( n = 6) received 1000 mg/d methylprednisolone (MPD) i.v. for three days followed by oral tapering with prednisone. We determined CGRP plasma levels in external jugular vein blood outside an attack and 6-sulfatoxymelatonin (aMT6s) – the stable metabolite of melatonin – in 12-hour day- and nighttime urine collection prior to and several times after MPD therapy and again when CH subjects were outside the bout in complete remission. CH patients recorded the frequency of attacks. Results In parallel to the reduction of headache frequency, administration of corticosteroids resulted in significantly decreased CGRP plasma levels and increased nocturnal aMT6s urine excretion in CH subjects. No significant changes were observed in controls. Conclusion Corticosteroids alter CGRP plasma and aMT6s urine levels in a cluster bout. These changes may indicate an effect of corticosteroids on trigeminal activation and hypothalamic dysfunction.

Modern migraine treatment

Ból ◽  
2019 ◽  
Vol 20 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Adam Stępień
Keyword(s):  
Monoclonal Antibodies ◽  
Chronic Disease ◽  
Migraine Attack ◽  
Sensory Nerve ◽  
Migraine Treatment ◽  
Trigeminovascular System ◽  
High Effectiveness ◽  
The Past ◽  
Calcitonin Gene ◽  
Functional Factors

Migraine is a chronic disease that periodically manifests as severe headaches accompanied by nausea, vomiting, photophobia and sensitivity to light and sound. Prevalence of migraine among women is estimated at 17% and 9% among men. Etiology and pathogenesis remain poorly elucidated. Involvement of genetic and functional factors of the trigeminovascular system including release of numerous neuropeptides from sensory nerve endings during the event has been demonstrated. The key role in the development of migraine attack is attributed to the calcitonin gene-related peptide and serotonin. Monoclonal antibodies directed against GCRP peptide and receptor – erenumab, galacenezumab, and fremanezumab, have been implemented in the therapy of episodic as well as chronic migraine in the past year. All pivotal trials demonstrated their safety as well as high effectiveness in the reduction of the number of days affected by headaches and migraine attacks.

scholarly journals Sleep disturbance management in patients with trigeminal autonomic cephalalgias

2021 ◽  
pp. 100-108
Author(s):  
N. V. Vashchenko ◽  
A. M. Uzhakhov ◽  
Ju. E. Azimova
Keyword(s):  
Cluster Headache ◽  
Vagus Nerve ◽  
Sleep Disturbances ◽  
Primary Headaches ◽  
Prophylactic Therapy ◽  
Trigeminal Autonomic Cephalalgias ◽  
Trigeminovascular System ◽  
Acute Therapy

Trigeminal autonomic cephalalgias (TACs) are rare but are the most intense primary headaches that severely limit patients’ ability to work and be socially active. This article reviews the modern classification of TACs, based on the International Classification of Headache Disorders-3, and the key differences between TAC types, as well as the pathophysiological mechanisms – the role of the trigeminovascular system, autonomic nervous system, hypothalamus and vagus nerve – and their relation to circadian rhythms. The sleep disturbances that can occur in patients with TACs, exacerbating the course of the disease, and the role of melatonin, hypothalamus and suprachiasmatic nucleus in these conditions are also discussed. In addition, current therapies for cluster headache are described, which include acute therapy and prophylactic therapy, with recommendations regarding the timing of prophylactic therapy discontinuation. The review also includes the available data on melatonin as well as new therapies such as CGRP monoclonal antibodies and neuromodulation, which includes the two most promising techniques: non-invasive vagus nerve stimulation and sphenopalatine ganglion microstimulation. Furthermore, the authors present the clinical case of a patient with chronic cluster headache, which was significantly reduced in frequency and intensity when melatonin was added to the therapy.

scholarly journals Neuropeptide changes in an improved migraine model with repeat stimulations

2021 ◽  
Vol 12 (1) ◽  
pp. 523-532
Author(s):  
Yichen Guo ◽  
Yawen Cheng ◽  
Jiaqi An ◽  
Yi Qi ◽  
Guogang Luo
Keyword(s):  
Rat Model ◽  
Medical Condition ◽  
Future Research ◽  
Trigeminal Ganglia ◽  
Trigeminovascular System ◽  
Dynamic Changes ◽  
Repeated Stimulation ◽  
Calcitonin Gene ◽  
Pituitary Adenylate Cyclase ◽  
Stimulation Of

Abstract Migraine is a medical condition with a severe recursive headache. The activation of the trigeminovascular system is an important mechanism. The neuropeptide calcitonin gene-related peptide (CGRP) plays a crucial role in the pathogenesis of migraine. Several other neuropeptides are also involved; however, their roles in migraine remain unclear. In this study, using a rat model of migraine induced by electrical stimulation of the trigeminal ganglia (TG) and an improved version induced with repeated stimulation, we observed the dynamic changes of these peptides in TG and blood. We demonstrated that the expression of CGRP, pituitary adenylate cyclase activating polypeptide (PACAP), neuropeptide Y (NPY), vasoactive intestinal peptide, and nociceptin in TG was significantly elevated and peaked at different time points after a single stimulation. Their levels in the blood plasma were significantly increased at 12 h after stimulation. The peptides were further elevated with repeated stimulation. The improved rat model of migraine with repeated stimulation of TG resulted in a more pronounced elevation of CGRP, PACAP, and NPY. Thus, the dynamic changes in neuropeptides after stimulation suggest that these neuropeptides may play an important role in the pathogenesis of migraine. Additionally, the migraine model with repetitive stimulation would be a novel model for future research.

scholarly journals Modern ideas about cluster headache. Literature review

2019 ◽  
Vol 2 (19) ◽  
pp. 19-23
Author(s):  
A. Savitskaya ◽  
E. G. Filatova
Keyword(s):  
Cluster Headache ◽  
Channel Blocker ◽  
Prophylactic Therapy ◽  
Review Of The Literature ◽  
Delay In Diagnosis ◽  
Leading Role ◽  
Separate Form ◽  
History Of ◽  
Acute Attacks

The article presents a review of the literature where, starting with the publication of Ekbom K. (1947), the history of the allocation of cluster headache into a separate form of primary head pain is described, modern diagnostic criteria are presented, the pathogenesis, clinical features of the disease are described. It is shown that due to the rarity of this type of headache and low awareness of doctors, the delay in diagnosis is on average 6–7 years. Patients are prescribed a lot of unnecessary examinations and expert consultations: oculists, ENT doctors, neurosurgeons, psychiatrists, etc. Favorite incorrect diagnoses are migraine and trigeminal neuralgia. The evidence of the leading role of the hypothalamus in the pathogenesis of cluster headache is presented. The principles of therapy are discussed: for the relief of acute attacks, triptans are used as in migraine, the leader of prophylactic therapy is a calcium channel blocker verapamil. In chronic forms and attacks resistant to pharmacological treatment, neurostimulation methods are used.

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