Background

Calcitonin gene-related peptide is recognized as a key player in migraine, yet the mechanisms and sites of calcitonin gene-related peptide action remain unknown. The efficacy of calcitonin gene-related peptide-blocking antibodies as preventative migraine drugs supports a peripheral site of action, such as the trigeminovasculature. Given the apparent disconnect between the importance of vasodilatory peptides in migraine and the prevailing opinion that vasodilation is an epiphenomenon, the goal of this study was to test whether vasodilation plays a role in calcitonin gene-related peptide-induced light aversive behavior in mice.

Methods

Systemic mean arterial pressure and light aversive behavior were measured after intraperitoneal administration of calcitonin gene-related peptide and vasoactive intestinal peptide in wild-type CD1 mice. The functional significance of vasodilation was tested by co-administration of a vasoconstrictor (phenylephrine, endothelin-1, or caffeine) with calcitonin gene-related peptide to normalize blood pressure during the light aversion assay.

Results

Both calcitonin gene-related peptide and vasoactive intestinal peptide induced light aversion that was associated with their effect on mean arterial pressure. Notably, vasoactive intestinal peptide caused relatively transient vasodilation and light aversion. Calcitonin gene-related peptide-induced light aversion was still observed even with normalized blood pressure. However, two of the agents, endothelin-1 and caffeine, did reduce the magnitude of light aversion.

Conclusion

We propose that perivascular calcitonin gene-related peptide causes light-aversive behavior in mice by both vasomotor and non-vasomotor mechanisms.

中文翻译：

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外周CGRP在小鼠偏头痛样畏光中的血管作用。

背景

降钙素基因相关肽被认为是偏头痛的关键因素，但降钙素基因相关肽作用的机制和位点仍然未知。降钙素基因相关肽阻断抗体作为偏头痛预防药物的功效支持外周作用部位，例如三叉血管系统。鉴于血管舒张肽在偏头痛中的重要性与血管舒张是一种附带现象的普遍观点之间明显脱节，本研究的目的是测试血管舒张是否在小鼠降钙素基因相关肽诱导的光厌恶行为中起作用。

方法

在野生型 CD1 小鼠腹腔注射降钙素基因相关肽和血管活性肠肽后，测量全身平均动脉压和光厌恶行为。通过血管收缩剂（苯肾上腺素、内皮素-1 或咖啡因）与降钙素基因相关肽的共同给药来测试血管舒张的功能意义，以在避光试验期间使血压正常化。

结果

降钙素基因相关肽和血管活性肠肽均诱导光厌恶，这与其对平均动脉压的影响有关。值得注意的是，血管活性肠肽引起相对短暂的血管舒张和光厌恶。即使血压正常，仍观察到降钙素基因相关肽诱导的光厌恶。然而，两种药物，内皮素-1 和咖啡因，确实降低了厌恶光的程度。

结论

我们提出血管周围降钙素基因相关肽通过血管舒缩机制和非血管舒缩机制在小鼠中引起光厌恶行为。