背景:垂体腺苷酸环化酶激活多肽-38(PACAP38)在健康志愿者中引起头痛,但PACAP38导致头痛的确切机制尚不清楚。我们调查了舒马曲坦和酮咯酸对健康志愿者PACAP38引起的头痛的预防作用。此外,我们使用高分辨率磁共振血管造影研究了血管机制对PACAP38诱发的头痛的影响.
方法:将34名健康志愿者分为两组(A和B),并在20分钟内接受PACAP38(10picomol/kg/min)的输注。A组在输注PACAP38前20分钟静脉注射舒马曲坦(4mg)或酮咯酸(30mg)。B组在输注PACAP38后90分钟接受舒马曲坦或酮咯酸输注。在这两个实验中,我们使用了一个随机的,双盲,交叉设计。我们记录了头痛的特征和脑外动脉的周长。
结果:我们发现A组PACAP38引起的头痛的AUC(0-6h)没有差异,用舒马曲坦或酮咯酸预处理(p=0.297)。舒马曲坦和酮咯酸在PACAP38诱导的MMA周长变化(AUCBaseline-110分钟)中没有差异(p=0.227),STA(p=0.795)和MCA(p=0.356)。B组,与舒马曲坦相比,酮咯酸治疗后可减少PACAP38-头痛(p<0.001)。与酮咯酸相比,舒马曲坦治疗后显着降低了STA(p=0.039)和MMA(p=0.015)的周长,但没有降低MCA(p=0.981)的周长。在探索性分析中,我们发现,与未治疗(AUC0-90min)相比,使用舒马曲坦预处理可减少PACAP38引起的头痛.
结论:与舒马曲坦相比,酮咯酸后处理在减轻PACAP38引起的头痛方面更有效。酮咯酸在不影响PACAP38诱导的动脉扩张的情况下发挥作用,而舒马曲坦治疗后减弱了PACAP38诱导的MMA和STA的扩张。舒马曲坦预处理可减轻PACAP38引起的头痛,而不影响PACAP38引起的动脉扩张。我们的发现表明,酮咯酸和舒马曲坦可以减轻健康志愿者中PACAP38引起的头痛,而没有血管作用。
背景:Clinicaltrials.gov(NCT03585894)。2018年7月13日注册
BACKGROUND: Pituitary adenylate cyclase-activating polypeptide-38 (
PACAP38) induces headache in healthy volunteers but the precise mechanisms by which
PACAP38 leads to headache are unclear. We investigated the headache preventive effect of sumatriptan and ketorolac on
PACAP38-induced headache in healthy volunteers. In addition, we explored contribution of vascular mechanisms to PACAP38-induced headache using high resolution magnetic resonance angiography.
METHODS: Thirty-four healthy volunteers were divided in two groups (A and B) and received infusion of PACAP38 (10 picomol/kg/min) over 20 min. Group A was pretreated with intravenous sumatriptan (4 mg) or ketorolac (30 mg) 20 min before infusion of PACAP38. Group B received infusion of sumatriptan or ketorolac as post-treatment 90 min after infusion of PACAP38. In both experiments, we used a randomized, double-blind, cross-over design. We recorded headache characteristics and circumference of extra-intracerebral arteries.
RESULTS: We found no difference in AUC (0-6 h) of PACAP38-induced headache in group A, pretreated with sumatriptan or ketorolac (p = 0.297). There was no difference between sumatriptan and ketorolac in PACAP38-induced circumference change (AUCBaseline-110 min) of MMA (p = 0.227), STA (p = 0.795) and MCA (p = 0.356). In group B, post-treatment with ketorolac reduced PACAP38-headache compared to sumatriptan (p < 0.001). Post-treatment with sumatriptan significantly reduced the circumference of STA (p = 0.039) and MMA (p = 0.015) but not of MCA (p = 0.981) compared to ketorolac. In an explorative analysis, we found that pre-treatment with sumatriptan reduced PACAP38-induced headache compared to no treatment (AUC0-90min).
CONCLUSIONS: Post-treatment with ketorolac was more effective in attenuating PACAP38-induced headache compared to sumatriptan. Ketorolac exerted its effect without affecting PACAP38-induced arterial dilation, whereas sumatriptan post-treatment attenuated
PACAP38-induced dilation of MMA and STA. Pre-treatment with sumatriptan attenuated
PACAP38-induced headache without affecting
PACAP38-induced arterial dilation. Our findings suggest that ketorolac and sumatriptan attenuated PACAP38-induced headache in healthy volunteers without vascular effects.
BACKGROUND: Clinicaltrials.gov (NCT03585894). Registered 13 July 2018.