Pharmacological prophylaxis of chronic migraine: a review of double-blind placebo-controlled trials
ABSTRACT Chronic migraine is an important public health problem. The aim of treatment should be to reduce migraine frequency and its negative impact on functioning, as well as to limit the use of acute medications. These goals may be accomplished by introducing effective prophylaxis. The aim of the present article is to critically review the published evidence on the pharmacological prophylaxis of chronic migraine, analysing published double-blind, placebo-controlled studies on adult patients. The results of the review indicate that tizanidine, gabapentin, valproic acid, and particularly topiramate are effective prophylactics against chronic migraine, with improvements in several endpoints that were significantly superior to those achieved by placebo. However, the different results found by different trials, as well as several methodological problems inherent in the trials, suggest the need for further research to provide clear indications from large, multicentre, controlled trials with homogeneous inclusion criteria and adequate endpoints.
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ABSTRACT: Valproate is widely used for migraine treatments, although precise mechanisms of its anticephalgic action are poorly understood. Migraine attacks are thought to occur due to trigemino-vascular system activation, which in turn, stimulates nociceptive transmission in trigemino-thalamo-cortical pathway. The ventroposteromedial (VPM) nucleus of the thalamus is considered to play a prominent role in neurobiology of headaches by serving as the highest subcortical relay for conveying nociceptive information from intra- and extracranial structures to the cortex. While it has been demonstrated that valproate can modulate trigemino-vascular nociceptive neurotransmission in the VPM, its effects have been investigated using only intrathalamic ejection of the compound in pentobarbitone sodium anesthetized rats. The objective of our study was to evaluate the effects of intravenously administered valproate on both ongoing firing of the VPM neurons and their activity induced by electrical stimulation of the dura mater. The experiments were performed on rats under nonbarbiturate anesthesia. To define the dose-dependent properties and longevity of the studied effects of valproate, two distinguished dosing regiments were used: bolus (single infusion at a dose of 300mg/kg) and cumulative (thrice-repeated administration of 100mg/kg performed 30min apart). Intravenous administration of valproate produced the dose-dependent suppression of both the ongoing activity of the thalamic VPM neurons and their responses to electrical stimulation of the dura mater. This effect was fast-developing (within 5min) and short-lasting (no longer than 30min). These data suggest that intravenous administration of valproate could produce a reduction of the thalamo-cortical nociceptive transmission associated with trigemino-vascular activation.European journal of pharmacology 05/2013; DOI:10.1016/j.ejphar.2013.05.019 · 2.68 Impact Factor
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ABSTRACT: The authors have been working on the problem of spatial reconstruction of interneuronal contacts and, in particular, the synaptic contacts formed by climbing fibers on dendritic spines of Purkinje cells. Rana temporaria cerebellar cortex served as the experimental material. Preparations were studied using an electron microscope and photographed at ×8000 and ×15000 magnification factors. Spatial reconstruction of synaptic contacts was performed by visually comparing observed structures and superpositioning micrographs of fifteen successive slices. Distinct features of these synapses are identified and discussedNeuroinformatics and Neurocomputers, 1992., RNNS/IEEE Symposium on; 11/1992
Conference Paper: Design and analysis of a novel superconducting generator[Show abstract] [Hide abstract]
ABSTRACT: An ambient-temperature salient-pole iron rotor excited by a single superconducting winding is retrofittable into a conventional stator. The concept is illustrated by application to a prototype design of a 1.5 MVA superconducting generator. The fault test response transient is obtained by a frequency response method based on finite element magnetic diffusion solutionsElectric Machines and Drives Conference Record, 1997. IEEE International; 06/1997