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Migraine Disorders: HELP
Articles by Michael J. M. Fischer
Based on 6 articles published since 2008
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Between 2008 and 2019, M. J. M. Fischer wrote the following 6 articles about Migraine Disorders.
 
+ Citations + Abstracts
1 Review Neuropeptide effects in the trigeminal system: pathophysiology and clinical relevance in migraine. 2011

Messlinger, Karl / Fischer, Michael J M / Lennerz, Jochen K. ·Institute of Physiology and Pathophysiology, University of Erlangen-Nuernberg, Erlangen, Germany. Messlinger@physiologie1.uni-erlangen.de ·Keio J Med · Pubmed #21979827.

ABSTRACT: The neuropeptides substance P, calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) have been considered as important mediators in migraine and other primary headaches. CGRP and VIP have been found at increased concentrations in jugular venous plasma during attacks of migraine or cluster headache, and CGRP receptor antagonists have recently been shown to be effective in migraine therapy. Substance P and CGRP are produced from a subset of trigeminal afferents, whereas VIP derives from parasympathetic efferents. Release of these neuropeptides in the meninges can cause arterial vasodilatation, mast cell degranulation and plasma extravasation in animal experiments, but only CGRP seems to be relevant in migraine. Animal models have confirmed the important role of CGRP in meningeal nociception. The activity of spinal trigeminal neurons is a sensitive integrative measure of trigeminal activity and is partly under the control of CGRP, most likely via central mechanisms. CGRP released from central terminals of trigeminal afferents in the spinal trigeminal nucleus seems to facilitate nociceptive transmission via presynaptic mechanisms. The central effect of CGRP is substantiated by suppression of nociceptive c-fos activation and neuronal activity in the spinal trigeminal nucleus following CGRP receptor inhibition. These proposed functions are supported by the localization of CGRP receptor components in the rat cranial dura mater, trigeminal ganglion and spinal trigeminal nucleus. The currently available data indicate multiple sites of CGRP action in trigeminal nociception and the pathogenesis of migraine; however, central CGRP receptors are likely to be the essential targets in the treatment of migraine using CGRP receptor antagonists.

2 Review [Neuropeptide effects on the trigeminal system: pathophysiology and clinical significance for migraine]. 2011

Messlinger, K / Fischer, M J M / Lennerz, J K. ·Institut für Physiologie und Pathophysiologie, Universität Erlangen-Nürnberg, Erlangen, Deutschland Messlinger@physiologie1.uni-erlangen.de ·Schmerz · Pubmed #21818718.

ABSTRACT: Neuropeptides, such as calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal polypeptide (VIP) are considered important mediators in primary headaches. Increased concentrations of CGRP have been found in jugular venous plasma during attacks of migraine and, concomitant with VIP elevation, during cluster headache. Substance P and CGRP are produced from subsets of trigeminal afferents whereas VIP derives from parasympathetic efferents. Release of these neuropeptides in the meninges causes arterial vasodilatation, mast cell degranulation and plasma extravasation in animal experiments. Particularly CGRP seems to be important, as receptor antagonists have recently been shown to have a therapeutic effect on migraine. Animal models have confirmed the role of CGRP in meningeal nociception. The activity of spinal trigeminal neurons is a sensitive integrative measure of trigeminal activity and CGRP released from central terminals of trigeminal afferents in the spinal trigeminal nucleus has been shown to facilitate nociceptive transmission, most likely by a presynaptic action. The proposed CGRP functions are supported by the distribution of CGRP receptor components localized in the rat cranial dura mater, the trigeminal ganglion and the spinal trigeminal nucleus. The currently available data indicate multiple sites of CGRP action in trigeminal nociception and the pathogenesis of migraine but central CGRP receptors are probably the essential targets in the treatment of migraine using CGRP receptor antagonists.

3 Review Calcitonin gene-related peptide receptor antagonists for migraine. 2010

Fischer, Michael J M. ·Department of Pharmacology, University of Cambridge, Cambridge, UK. mjmf2@cam.ac.uk ·Expert Opin Investig Drugs · Pubmed #20482328.

ABSTRACT: IMPORTANCE OF THE FIELD: Migraine is a highly prevalent disabling condition, and the current treatment options are not satisfactory. The role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology is well established. CGRP receptor antagonists address this new target and have the potential to improve therapy for both responders and non-responders to previous options. AREAS COVERED IN THIS REVIEW: This review describes CGRP, its receptors and their role in the pathophysiology of migraine. CGRP receptor antagonists are a recent development; all reported antagonists are reported in chronological order. The experimental evidence, as well as all clinical trials since the first proof-of-concept study in 2004, is discussed. WHAT THE READER WILL GAIN: An overview of the CGRP system and why it provides an attractive drug target for headache. The main focus is on the currently presented CGRP receptor antagonists and clinical evidence for this new therapeutic option. TAKE HOME MESSAGE: CGRP receptor antagonists will provide an additional and valuable therapeutic option for the treatment of headaches.

4 Article Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus. 2018

Fischer, Michael J M / Schmidt, Jakob / Koulchitsky, Stanislav / Klussmann, Sven / Vater, Axel / Messlinger, Karl. ·Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Universitätstrasse 17, D-91054, Erlangen, Germany. · Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria. · Department of Pharmacology, University of Liège, Liège, Belgium. · Aptarion Biotech, Berlin, Germany. · Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Universitätstrasse 17, D-91054, Erlangen, Germany. karl.messlinger@fau.de. ·J Headache Pain · Pubmed #29335794.

ABSTRACT: BACKGROUND: Calcitonin gene-related peptide (CGRP) plays a major role in the pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons integrate nociceptive afferent input from trigeminal tissues including intracranial afferents, and their activity is thought to reflect facial pain and headache in man. CGRP receptor inhibitors and anti-CGRP antibodies have been demonstrated to be therapeutically effective in migraine. In parallel, CGRP receptor inhibition has been shown to lower spinal trigeminal neuron activity in animal models of meningeal nociception. METHODS: In a rat model of meningeal nociception, single cell activity of neurons in the spinal trigeminal nucleus with meningeal afferent input was recorded to test a further pharmacological approach, scavenging CGRP with a CGRP-binding L-RNA oligonucleotide, the L-aptamer NOX-C89. Cumulative ascending doses of NOX-C89 were intravenously infused. RESULTS: Spontaneous activity of spinal trigeminal neurons did not change after 0.05 mg/kg NOX-C89, however, after additional infusion of 0.5 mg/kg and 5 mg/kg NOX-C89, spontaneous activity was dose-dependently reduced. Identical doses of a control L-aptamer had no effect. This pharmacological effect of NOX-C89 was observed 10-25 min after infusion, but no difference was detected in the period 0-5 min. For comparison, the previously investigated CGRP receptor antagonist olcegepant had reduced activity within 5 min after infusion. Alongside the reduced spontaneous activity, after infusion of NOX-C89 the heat-induced neuronal activity was abolished. CONCLUSIONS: Scavenging CGRP by mirror-image RNA aptamers provides further evidence that this approach can be used to control spinal trigeminal activity.

5 Article Increase in CGRP- and nNOS-immunoreactive neurons in the rat trigeminal ganglion after infusion of an NO donor. 2011

Dieterle, Anne / Fischer, Michael J M / Link, Andrea S / Neuhuber, Winfried L / Messlinger, Karl. ·Institute of Physiology and Pathophysiology, University of Erlangen-Nuernberg, Universitaetsstrasse 17, Erlangen, Germany. ·Cephalalgia · Pubmed #20974582.

ABSTRACT: BACKGROUND: Nitrovasodilators, such as glyceroltrinitrate (GTN), which produce nitric oxide (NO) in the organism, are known to cause delayed headaches in migraineurs, accompanied by increased plasma levels of calcitonin gene-related peptide (CGRP) in the cranial venous outflow. Increases in plasma CGRP and NO metabolites have also been found in spontaneous migraine attacks. In a rat model of meningeal nociception, infusion of NO donors induced activity of neurons in the spinal trigeminal nucleus. METHODS: Isoflurane-anaesthetised rats were intravenously infused with GTN (250 µg/kg) or saline for two hours and fixed by perfusion after a further four hours. Cryosections of dissected trigeminal ganglia were immunostained for detection of CGRP and neuronal NO synthase (nNOS). The ganglion neurons showing immunofluorescence for either of these proteins were counted. RESULTS: The proportions of CGRP- and nNOS- as well as double-immunopositive neurons were increased after GTN infusion compared to saline treatment in all parts of the trigeminal ganglion (CGRP) or restricted to the ophthalmic region (nNOS). The size of immunopositive neurons was not significantly different compared to controls. CONCLUSION: High levels of NO may induce the expression or availability of CGRP and nNOS. Similar changes may be involved in nitrovasodilator-induced and spontaneous headache attacks in migraineurs.

6 Article Calcitonin gene-related peptide receptor antagonist olcegepant acts in the spinal trigeminal nucleus. 2009

Sixt, Marie-Luise / Messlinger, Karl / Fischer, Michael J M. ·Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Universitätstrasse 17, 91054 Erlangen, Germany. ·Brain · Pubmed #19737844.

ABSTRACT: Several lines of evidence suggest a major role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine and other primary headaches. Inhibition of CGRP receptors by olcegepant and telcagepant has been successfully used to treat acute migraine and to reduce the activity of spinal trigeminal neurons involved in meningeal nociception in rodents. The site of CGRP receptor inhibition is unclear, however. In adult Wistar rats anaesthetized with isofluorane systemic intravenous infusion (0.9 mg/kg) or unilateral facial injection (1 mM in 100 microl) of capsaicin was used to induce activity in the trigeminal nociceptive system. Animals were pre-treated either by saline or olcegepant. In comparison with vehicle infusion or the non-injected side of the face, capsaicin significantly increased the expression of the activation markers Fos in the spinal trigeminal nucleus and phosphorylated extracellular signal-regulated kinase in the trigeminal ganglion. Pre-treatment with olcegepant (900 microg/kg) inhibited the capsaicin-induced expression of Fos throughout the spinal trigeminal nucleus by 57%. In contrast, the expression of phosphorylated extracellular signal-regulated kinase in the trigeminal ganglion was not changed by olcegepant pre-treatment. CGRP receptor inhibition, which has been shown to decrease spinal trigeminal activity, is likely to occur in the central nervous system rather than in the periphery including the trigeminal ganglion. This may be important for future therapeutic interventions with CGRP receptor antagonists in migraine.