The calcitonin gene-related peptide receptor antagonist MK-8825 decreases spinal trigeminal activity during nitroglycerin infusion

The Journal of Headache and Pain

Research Article

Stephanie Albrecht¹  Karl Messlinger¹  Stephan Feistel¹ 

[1] Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Universitätsstr 17, 91054, Erlangen, Germany;

关键词: CGRP receptor antagonist;    Nitroglycerin;    Trigeminal nucleus caudalis;    Extracellular recording;    Headache;    Migraine;   

DOI  :  10.1186/1129-2377-14-93

 received in 2013-10-02, accepted in 2013-11-16,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundCalcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches. Migraineurs respond to infusion of nitroglycerin with delayed headaches, and inhibition of CGRP receptors has been shown to be effective in migraine therapy. In animal experiments nitrovasodilators like nitroglycerin induced increases in spinal trigeminal activity, which were reversed after inhibition of CGRP receptors. In the present study we asked if CGRP receptor inhibition can also prevent spinal trigeminal activity induced by nitroglycerin.MethodsIn isoflurane anaesthetised rats extracellular recordings were made from neurons in the spinal trigeminal nucleus with meningeal afferent input. The non-peptide CGRP receptor inhibitor MK-8825 (5 mg/kg) dissolved in acidic saline (pH 3.3) was slowly infused into rats one hour prior to prolonged glyceryl trinitrate (nitroglycerin) infusion (250 μg/kg/h for two hours).ResultsAfter infusion of MK-8825 the activity of spinal trigeminal neurons with meningeal afferent input did not increase under continuous nitroglycerin infusion but decreased two hours later below baseline. In contrast, vehicle infusion followed by nitroglycerin was accompanied by a transient increase in activity.ConclusionsCGRP receptors may be important in an early phase of nitroglycerin-induced central trigeminal activity. This finding may be relevant for nitroglycerin-induced headaches.

【 授权许可】

Unknown   
© Feistel et al.; licensee Springer. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.