Headache and non-headache symptoms provoked by nitroglycerin in migraineurs: A human pharmacological triggering study.

Nazia Karsan,Pyari R Bose,Peter J Goadsby,Charlotte Thompson,Jayde Newman

doi:10.1177/0333102420910114

Nazia Karsan, Pyari R Bose + Show 3 more

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https://doi.org/10.1177/0333102420910114

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Abstract

BackgroundStudying a spontaneous migraine attack is challenging, particularly the earliest components. Nitroglycerin is a potent, reliable and reproducible migraine trigger of the entirety of the migraine attack, making its use experimentally attractive.MethodsFifty-three subjects with migraine with a history of spontaneous premonitory symptoms were exposed to a 0.5 mcg/kg/min nitroglycerin infusion. Eighty-three percent (n = 44) developed typical premonitory and headache symptomatology. Fifty-seven percent (n = 25) were invited back to further study visits, during which they were re-exposed to nitroglycerin or placebo infusion in a double-blind randomised design. The phenotype of premonitory symptoms and headache was captured and compared to spontaneous attacks and between triggered attacks using agreement analysis.ResultsMore premonitory symptoms were triggered with nitroglycerin than placebo (mean symptom difference = 4, t20 = 7.06, p < 0.001). The agreement in triggering for the most commonly reported premonitory symptoms (concentration difficulty and tiredness) was >66%. The retriggering agreement for all but one premonitory symptom was >60%. The agreement in timing to onset of premonitory symptoms was reliable across two triggered attacks. The agreement with spontaneous attacks and between attacks for headache and its associated symptoms, including laterality, was less reliable.ConclusionsNitroglycerin can reliably and reproducibly provoke premonitory symptomatology associated with migraine. This forms an ideal model to study the earliest manifestations of migraine attacks.

Highlights

Non-headache symptomatology associated with migraine has been noted since at least the 19th century [1], while systematic studies of the prevalence and phenotype have only really emerged over the last 30 years [2,3]
This study looking at premonitory symptoms triggered with NTG amongst migraineurs exposed healthy controls to nitroglycerin, but data from healthy controls regarding the development of non-painful symptomatology following nitroglycerin exposure is not available [11]
We report the detailed phenotype of premonitory symptoms, headache and associated headache symptoms provoked by nitroglycerin amongst migraineurs, with additional analyses concerning re-exposure reliability of symptomatology

Summary

Introduction

Non-headache symptomatology associated with migraine has been noted since at least the 19th century [1], while systematic studies of the prevalence and phenotype have only really emerged over the last 30 years [2,3]. Capturing the entirety of a migraine attack to appreciate these symptoms fully and perform detailed phenotyping prospectively, as well studying spontaneous headache experimentally, are challenging issues. Nitroglycerin administered intravenously at 0.5 mcg/kg/min over 20 minutes is able to provoke migraine headache in up to 83% of sufferers [11,12,13] and has been shown to be able to trigger premonitory symptoms in some sufferers [11]. The phenotype of premonitory symptoms and headache was captured and compared to spontaneous attacks and between triggered attacks using agreement analysis. The agreement in timing to onset of premonitory symptoms was reliable across two triggered attacks. Conclusions: Nitroglycerin can reliably and reproducibly provoke premonitory symptomatology associated with migraine. This forms an ideal model to study the earliest manifestations of migraine attacks

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