Jones M G, Andreou A P, McMahon S B, Spanswick D
Neurorestoration Group, Wolfson Centre for Age-Related Disease, Kings College London, London, UK.
Zenith NeuroTech, Wolfson Centre for Age-Related Disease, Kings College London, London, UK.
J Headache Pain. 2016 Dec;17(1):96. doi: 10.1186/s10194-016-0686-x. Epub 2016 Oct 21.
Migraineurs 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.
In 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.
Glyceryl 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.
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.
偏头痛患者对一氧化氮供体硝酸甘油高度敏感，硝酸甘油会引发许多患者的偏头痛发作。在动物研究中，硝酸甘油会增加三叉神经血管通路中的神经元活动，并提高脑干中的神经递质水平。许多偏头痛患者的眨眼反射也存在改变，已知这涉及脑干回路。我们研究了硝酸甘油对麻醉大鼠诱发眨眼的影响，以确定这种反射是否可作为评估潜在抗偏头痛治疗药物的新型动物模型的基础。
在麻醉大鼠中，记录与角膜吹气诱发的反射性眨眼相关的肌电图。给大鼠输注硝酸甘油、舒马曲坦加硝酸甘油或载体对照。测量这些处理后反射性眨眼相关肌电图幅度的变化。
硝酸甘油在输注后2小时增强了诱发的反射性眨眼相关肌电图反应。同时输注舒马曲坦和硝酸甘油可消除该效应。
这些结果表明，对大鼠诱发的肌电图活动进行简单的皮肤表面测量可以可靠地检测到可被一氧化氮供体增强的诱发眨眼反射。这种新型模型可能是评估潜在抗偏头痛治疗药物的有效工具。
