Abstract
BackgroundMigraineurs are highly sensitive to the nitric oxide donor glyceryl trinitrate which triggers attacks in many sufferers. In animal studies, glyceryl trinitrate increases neuronal activity in the trigeminovascular pathway and elevates neurotransmitter levels in the brainstem. Many migraineurs also display alterations in blink reflexes, known to involve brainstem circuits. We investigated the effect of GTN on evoked blinks in the anaesthetised rat to determine whether such reflexes may prove useful as the basis for a novel animal model to evaluate potential anti-migraine therapeutic agents.MethodIn anaesthetised rats the electromyogram associated with the reflex blink evoked by corneal airpuff was recorded. Rats were infused with glyceryl trinitrate, sumatriptan plus glyceryl trinitrate or vehicle control. Changes in the magnitude of the reflex blink-associated electromyogram following these treatments were measured.ResultsGlyceryl trinitrate potentiated the evoked reflex blink-associated EMG response from 2 h after infusion. That effect was abolished by simultaneous infusion of sumatriptan with glyceryl trinitrate.ConclusionsThese results show that simple skin surface measurements of evoked electromyographic activity in the rat can reliably detect the evoked blink reflex that can be potentiated by nitric oxide donors. This novel model may be an effective tool for evaluating putative anti-migraine therapeutic agents.
Highlights
Migraineurs are highly sensitive to the nitric oxide donor glyceryl trinitrate which triggers attacks in many sufferers
These results show that simple skin surface measurements of evoked electromyographic activity in the rat can reliably detect the evoked blink reflex that can be potentiated by nitric oxide donors
This novel model may be an effective tool for evaluating putative anti-migraine therapeutic agents
Summary
Migraineurs are highly sensitive to the nitric oxide donor glyceryl trinitrate which triggers attacks in many sufferers. The actual measurements are of an electromyographic activity, the blink reflex is an objective neurophysiological method that evaluates the connectivity of the lateral medulla and pons with the trigeminal and facial nerves It involves stimulation of the ipsilateral supraorbital branch of the trigeminal nerve which results in an afferent response along the trigeminal nerve to the trigeminal nucleus in the pons and the nucleus of the spinal tract of the trigeminal nerve in the brainstem. GTN infusion in healthy volunteers is shown to induce comparable changes in nociceptive blink reflex, to those found immediately before and during an attack in migraineurs [17] These reports, suggest the usefulness of the study of the blink reflex as a subtle neurophysiological outcome on central brainstem changes that occur in migraine patients, and, the potential modelling of these changes with the infusion of GTN
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