The trigeminovascular system has a pivotal role in the pathomechanism of migraine. The aim of the present study was to further develop existing models of migraine making them more suitable for testing the effects of compounds with presumed antimigraine activity in anaesthetised rats. Simultaneous recording of ongoing activity of spontaneously active neurons in the trigeminocervical complex as well as their discharges evoked by electrical stimulation of the dura mater via activation of A- and C-sensory fibres were carried out. Effects of sumatriptan, propranolol and topiramate were evaluated prior to and after application of a mixture containing inflammatory mediators on the dura. Propranolol (10 mg/kg s.c) and topiramate (30 mg/kg s.c.) resulted in a tendency to decrease the level of both spontaneous and evoked activity, while sumatriptan (1 mg/kg s.c.) did not exhibit any effect on recorded parameters. Application of an inflammatory soup to the dura mater boosted up spontaneous activity, which could be significantly attenuated by propranolol and topiramate but not by sumatriptan. In addition, all compounds prevented the delayed increase of spontaneous firing. In contrast to the ongoing activity, evoked responses were not augmented by inflammatory mediators. Nevertheless, inhibitory effect of propranolol and topiramate was evident when considering A- or C-fibre responses. Findings do not support the view that electrically evoked responses are useful for the measurement of trigeminal sensitization. It is proposed however, that inhibition of enhanced firing (immediate and/or delayed) evoked by inflammatory mediators as an endpoint have higher predictive validity regarding the clinical effectiveness of compounds.
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http://dx.doi.org/10.1016/j.brainres.2015.08.039 | DOI Listing |
Expert Rev Neurother
January 2025
Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain.
Introduction: The main treatment options for essential tremor (ET), which is probably one of the most common movement disorders, have been propranolol and primidone, for many years. This review aims to synthesize therapeutic attempts with other drugs.
Areas Covered: We have reviewed the current state of the pharmacological treatment of ET, both in patients and in experimental models of this disease, with special emphasis on the data published in the last 5 years.
J Headache Pain
December 2024
Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy.
Combination treatments for migraine prophylaxis present a promising approach to addressing the diverse and complex mechanisms underlying migraine. This review explores the potential of combining oral conventional prophylactics, onabotulinumtoxin A, monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway, and small molecule CGRP receptor antagonists (gepants). Among the most promising strategies, dual CGRP inhibition through mAbs and gepants may enhance efficacy by targeting both the CGRP peptide and its receptor, while the combination of onabotulinumtoxin A with CGRP treatments offers synergistic pain relief.
View Article and Find Full Text PDFCephalalgia
November 2024
Dept. of Systems Neuroscience, University Clinic Hamburg Eppendorf, Hamburg, Germany.
Background: In this study, we aimed to evaluate the differing global access to acute and preventive medications for migraine and tension-type headache.
Methods: A custom-built questionnaire created by members of the International Headache Society Juniors Group was sent to International Headache Society members worldwide, including a list of acute and preventive treatments for migraine and tension-type headache. This list was based on evidence-based medicine guidelines.
JMIR Form Res
November 2024
Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Background: Clinical trials demonstrate the efficacy and tolerability of medications targeting calcitonin gene-related peptide (CGRP) signaling for migraine prevention. However, these trials may not accurately reflect the real-world experiences of more diverse and heterogeneous patient populations, who often have higher disease burden and more comorbidities. Therefore, postmarketing safety surveillance is warranted.
View Article and Find Full Text PDFCan J Neurol Sci
November 2024
Ottawa Hospital, Division of Neurology, University of Ottawa, Ottawa, ON, Canada.
Objective: We have updated the migraine prevention guideline of the Canadian Headache Society from 2012, as there are new therapies available, and additionally, we have provided guidelines for the prevention of chronic migraine, which was not addressed in the previous iteration.
Methods: We undertook a systematic review to identify new studies since the last guideline. For studies identified, we performed data extraction and subsequent meta-analyses where possible.
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