Abstract
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.
Highlights
Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches
The clinical data are paralleled by animal experiments demonstrating the involvement of CGRP and NO in meningeal nociception, which is assumed to underlie the generation of headaches
The activity evoked by sodium nitroprusside (SNP) and nitroglycerin was decreased after CGRP receptor blockade to the preexisting level, suggesting an interaction of CGRP and NO mechanisms in neuronal activity evoked by nitrovasodilators [18]
Summary
Calcitonin 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. Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in the generation of migraine and other primary headaches [1,2], based on several clinical data. Infusion of the nitrovasodilators sodium nitroprusside (SNP) and nitroglycerin (glyceryl trinitrate, GTN) induced ongoing activity of spinal trigeminal neurons with meningeal afferent input [18], resembling the clinical experiments in migraineurs. The activity evoked by SNP and nitroglycerin was decreased after CGRP receptor blockade to the preexisting level, suggesting an interaction of CGRP and NO mechanisms in neuronal activity evoked by nitrovasodilators [18]
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