1,721,068 research outputs found
An update on migraine: current understanding and future directions
Full text linkMigraine is a common brain disorder with high disability rates which involves a series of abnormal neuronal networks, interacting at different levels of the central and peripheral nervous system. An increase in the interest around migraine pathophysiology has allowed researchers to unravel certain neurophysiological mechanisms and neurotransmitter involvement culminating in the recent development of novel therapies, which might substantially change the clinical approach to migraine patients. The present review will highlight the current aspects of migraine pathophysiology, covering an understanding of the complex workings of the migraine state and the brain regions responsible for them. We will further discuss the therapeutic agents which have appeared in the most recent years for migraine care, from calcitonin gene-related peptide (CGRP) receptor antagonists, gepants; through serotonin 5-HT1F receptor agonists, ditans, and CGRP or CGRP receptor monoclonal antibodies to invasive and non-invasive neuromodulation techniques
CGRP – a target for acute therapy in migraine: Clinical data
No full textBackground A better understanding of the mechanisms underlying the migraine attack has reinforced the concept that migraine is a complex brain disease, and has paved the way for the development of new migraine specific acute treatments. In recent years, targeting the calcitonin gene-related peptide and its receptors has been one of the most promising pharmacological strategies for both acute and preventive treatment of migraine. Findings Randomized double-blind placebo-controlled trials have demonstrated the superiority of small molecule calcitonin gene-related peptide receptor antagonists (gepants) over placebo in treating acute migraine attacks measured as the two-hour pain free endpoint. Gepants also improved migraine associated symptoms, such as nausea, photophobia and phonophobia. Two of the class have had their development stopped because of hepatotoxicity, which is emerging as being due to metabolites. Gepants have a good tolerability and can be safely used in patients with stable cardiovascular disease. Conclusion Exciting results have been obtained targeting the calcitonin gene-related peptide pathway to abort acute migraine attacks, thus reinforcing the relevance of mechanism-based treatments specific for migraine. </jats:sec
Topiramate for migraine prevention in fertile women: reproductive counseling is warranted.
No full textInvolvement of kainate glutamate receptors in the modulation of neuronal transmission in brain areas involved in migraine pathophysiology
No full textMigraine pathophysiology is thought to involve activation of the trigeminal fibres which
innervate dural structures. The nociceptive inflow from the meninges is relayed to the
trigeminocervical complex (TCC), before ascending to higher brain areas, including the
thalamus. Glutamate is implicated in the transmission of the nociceptive information
and thus an increased understanding of the nature and effects of glutamate receptors
activation has major implications in migraine pathophysiology and treatment. Here the
role of kainate receptors, a member of the ionotropic glutamate receptors subfamily,
was investigated in relaying sensory information upon activation of the
trigeminovascular system.
In order to study the role of kainate receptors on the periphery, we used the
neurogenic dural vasodilation (NDV) model, in which electrical stimulation of the dura
mater causes reproducible vasodilation, due to calcitonic gene-related peptide (CGRP)
release. In this set of experiments kainate receptor activation but not blockade was
effective in inhibiting NDV. Vasodilation induced by systemic administration of CGRP
was not changed by administration of a kainate receptor agonist.
In the TCC, local application by microiontophoresis of a selective kainate
receptor antagonist on second order neurons which were excited by meningeal electrical
stimulation, caused dual effects; 50% of the neurons tested were inhibited, whereas in a
second subpopulation, activation in response to meningeal stimulation was facilitated.
However, in all neurons tested, post-synaptic activation in response to kainate receptor
agonists application was selectively inhibited.
Microiontophoretic ejection of a kainate receptor antagonist in the
ventroposteromedial thalamus (VPM) was able to inhibit cell firing in response to dural
stimulation, as well as post-synaptic firing in response to kainate receptor activation.
Both effects were reversed when the kainate receptor antagonist was co-ejected with a
5-HT1B receptor antagonist.
We also carried electrophysiology studies in both the TCC and the VPM nucleus
in order to compare the effects of the clinically active kainate receptor antagonist
LY466195. Systemic and local application of LY466195 was able to inhibit cell firing
in response to dura mater stimulation in both the TCC and VPM nucleus. Moreover,
further to the kainate binding, a significant action of the compound on N-methyl-Daspartate
receptors was observed
The International Classification of Headache Disorders. 2nd Editing. 4 Working group on Other primary Headaches
No full textP/Q-type calcium-channel blockade in the periaqueductal gray facilitates trigeminal nociception: a functional genetic link for migraine?
No full textThe discovery of mis-sense mutations in the alpha1A subunit of the P/Q-type calcium channel in patients with familial hemiplegic migraine indicates the potential involvement of dysfunctional ion channels in migraine. The periaqueductal gray (PAG) region of the brainstem modulates craniovascular nociception and, through its role in the descending pain modulation system, may contribute to migraine pathophysiology. In this study we sought to investigate the possible link between the genetic mutations found in migraineurs and the PAG as a modulator of craniovascular nociception. We microinjected the P/Q-type calcium-channel blocker omega-agatoxin IVA into the rat ventrolateral PAG (vlPAG). We examined its effect on the nociceptive transmission of second-order neurons recorded in the trigeminal nucleus caudalis and activated by stimulation of the parietal dura mater. After injection of agatoxin into the vlPAG (n = 20) responses to dural stimulation were facilitated by 143% (p < 0.0001) for Adelta-fiber activity and 180% for C-fiber activity (p < 0.05). Similarly, spontaneous background activity increased by 163% (p < 0.0001). These results demonstrate that P/Q-type calcium channels in the PAG play a role in modulating trigeminal nociception and suggest a role for dysfunctional P/Q-type calcium channels in migraine pathophysiology.<br/
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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