Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark; Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark.
J Invest Dermatol. 2021 Jul;141(7):1687-1698. doi: 10.1016/j.jid.2021.02.002. Epub 2021 Feb 16.
The pathogenesis of rosacea is incompletely understood. Signaling neuropeptides, including PACAP, a regulator of vasodilation and edema, are upregulated in rosacea skin. Here, we evaluated PACAP38-induced rosacea features and examined whether a 5-HT receptor agonist could reduce these features.
A total of 35 patients with erythematotelangiectatic rosacea received an intravenous infusion of 10 pmol/kg/minute of PACAP38 followed by an intravenous infusion of 4 mg sumatriptan or placebo (saline) on two study days in a double-blind, randomized, placebo-controlled, and cross-over trial.
PACAP38 increased facial skin blood flow by 90%, dilated the superficial temporal artery by 56%, and induced prolonged flushing and facial edema. Compared with placebo, sumatriptan reduced PACAP38-induced facial skin blood flow for 50 minutes (P = 0.023), constricted the superficial temporal artery for 80 minutes (P = 0.010), and reduced duration of flushing (P = 0.001) and facial edema (P < 0.001).
We established a clinical experimental model of rosacea features and showed that sumatriptan was able to attenuate PACAP38-induced rosacea flushing and edema. Findings support a key role of PACAP38 in rosacea flushing pathogenesis. It remains unknown whether PACAP38 inhibition can improve rosacea.
The trial was registered at ClinicalTrials.govNCT03878784 in March 2019.
酒渣鼻的发病机制尚不完全清楚。信号神经肽，包括血管舒张和水肿的调节因子 PACAP，在酒渣鼻皮肤中上调。在这里，我们评估了 PACAP38 诱导的酒渣鼻特征，并研究了 5-HT 受体激动剂是否可以减轻这些特征。
共有 35 名红斑毛细血管扩张性酒渣鼻患者接受了 10 pmol/kg/minute 的 PACAP38 静脉输注，然后在双盲、随机、安慰剂对照和交叉试验的两天内接受了 4mg 舒马曲坦或安慰剂（生理盐水）的静脉输注。
PACAP38 使面部皮肤血流量增加了 90%，使颞浅动脉扩张了 56%，并引起了长时间的潮红和面部水肿。与安慰剂相比，舒马曲坦可使 PACAP38 诱导的面部皮肤血流量减少 50 分钟（P = 0.023），使颞浅动脉收缩 80 分钟（P = 0.010），并减少潮红持续时间（P = 0.001）和面部水肿（P < 0.001）。
我们建立了酒渣鼻特征的临床实验模型，并表明舒马曲坦能够减轻 PACAP38 诱导的酒渣鼻潮红和水肿。这些发现支持 PACAP38 在酒渣鼻潮红发病机制中的关键作用。尚不清楚 PACAP38 抑制是否可以改善酒渣鼻。
该试验于 2019 年 3 月在 ClinicalTrials.govNCT03878784 注册。
