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Two-hour infusion of vasoactive intestinal polypeptide induces delayed headache and extracranial vasodilation in healthy volunteers.
Cephalalgia ( IF 4.9 ) Pub Date : 2020-06-27 , DOI: 10.1177/0333102420937655
Lanfranco Pellesi 1 , Mohammad Al-Mahdi Al-Karagholi 1 , Basit Ali Chaudhry 1 , Cristina Lopez Lopez 2 , Josefin Snellman 2 , Jens Hannibal 3 , Faisal Mohammad Amin 1 , Messoud Ashina 1
Affiliation  

Background

In recent years, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) have gained special interest in headache science. VIP and PACAPs (two isoforms, PACAP27 and PACAP38) are related in structure and function, as are their receptors, but they show differences in vasodilating- and headache-inducing properties. Intravenous infusion of PACAP27 or PACAP38, but not VIP, induces a long-lasting dilation of cranial arteries and delayed headache. The relationship between the long-lasting cranial vasodilation and headache development is not fully clarified.

Methods

In a double-blinded, placebo-controlled, crossover study in 12 healthy volunteers, diameter changes of cranial arteries, occurrence of headache and the parasympathetic system were examined before, during and after a 2-hour continuous intravenous infusion of VIP and placebo. Primary endpoints were the differences in area under the curve for the superficial temporal artery diameter and headache intensity scores, as well as in headache incidence, between VIP and placebo.

Results

The superficial temporal artery diameter was significantly larger on the VIP day compared to placebo (p < 0.001) and the dilation lasted for more than 2 h. The incidence of headache was higher (p = 0.003) on the VIP day compared to the placebo day. The difference in headache intensity scores was more evident in the post-infusion period (120–200 min, p = 0.034) and in the post-hospital phase (4–12 h, p = 0.025). Cranial parasympathetic activity, measured through the production of tears, was higher during VIP compared to placebo (p = 0.033).

Conclusion

Continuous intravenous infusion of VIP over 2 h induced a long-lasting cranial vasodilation, activation of the cranial parasympathetic system, and delayed mild headaches in healthy volunteers.

Trial Registration: The study is registered at ClinicalTrials.gov (NCT03989817).



中文翻译:

血管活性肠多肽输注两小时可在健康志愿者中引起延迟性头痛和颅外血管舒张。

背景

近年来,血管活性肠肽 (VIP) 和垂体腺苷酸环化酶激活多肽 (PACAPs) 在头痛科学中引起了特别的兴趣。VIP 和 PACAPs(两种同工型,PACAP27 和 PACAP38)在结构和功能上是相关的,它们的受体也是如此,但它们在血管舒张和头痛诱导特性方面表现出差异。静脉输注 PACAP27 或 PACAP38(而非 VIP)会导致颅动脉长期扩张和延迟性头痛。持久的颅血管舒张与头痛发展之间的关系尚未完全阐明。

方法

在一项对 12 名健康志愿者进行的双盲、安慰剂对照、交叉研究中,在连续静脉输注 2 小时 VIP 和安慰剂之前、期间和之后检查了颅动脉直径变化、头痛和副交感神经系统的发生。主要终点是 VIP 和安慰剂之间颞浅动脉直径和头痛强度评分曲线下面积的差异,以及头痛发生率的差异。

结果

与安慰剂相比,VIP 日的颞浅动脉直径显着更大 ( p  < 0.001),扩张持续超过 2 小时。 与安慰剂日相比,VIP 日的头痛发生率更高(p = 0.003)。头痛强度评分的差异在输注后阶段(120-200 分钟,p  = 0.034)和出院后阶段(4-12 小时,p  = 0.025)更为明显。与安慰剂相比,VIP 期间通过眼泪的产生测量的颅副交感神经活动更高(p  = 0.033)。

结论

在健康志愿者中,连续静脉输注 VIP 超过 2 小时可引起持久的颅血管舒张、颅副交感神经系统激活和延迟轻度头痛。

试验注册:该研究在 ClinicalTrials.gov (NCT03989817) 上注册。

更新日期:2020-06-28
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