近年来,血管活性肠肽(VIP)和垂体腺苷酸环化酶激活多肽(PACAP)在头痛科学中引起了特别的兴趣。VIP和PACAP(两种亚型,PACAP27和PACAP38)在结构和功能上相关,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,而不是VIP,引起颅内动脉长期扩张和迟发性头痛。持久的颅血管舒张与头痛发展之间的关系尚未完全阐明。
在双盲中,安慰剂对照,在12名健康志愿者中进行交叉研究,颅内动脉的直径变化,之前检查了头痛和副交感神经系统的发生,在连续2小时静脉输注VIP和安慰剂期间和之后。主要终点是颞浅动脉直径和头痛强度评分的曲线下面积的差异,以及头痛的发病率,在VIP和安慰剂之间。
与安慰剂相比,VIP日的颞浅动脉直径明显更大(p<0.001),扩张持续2小时以上。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液后期间更为明显(120-200分钟,p=0.034)和住院后阶段(4-12小时,p=0.025)。颅副交感神经活动,通过眼泪的产生来衡量,与安慰剂相比,VIP期间更高(p=0.033)。
持续静脉输注VIP超过2小时可引起持久的头颅血管舒张,激活颅副交感神经系统,并延迟健康志愿者的轻度头痛。试验注册:该研究在ClinicalTrials.gov(NCT03989817)注册。
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.
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.
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).
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).