Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Headache Pain. 2017 Nov 23;18(1):110. doi: 10.1186/s10194-017-0821-3.
To review the role of PACAP38 in human models of primary headaches, discuss possible mechanisms of PACAP38-induced migraine, and outline future directions.
Experimental studies have established PACAP38 as a potent pharmacological "trigger" molecule of migraine-like attacks. These studies have also revealed a heterogeneous PACAP38 migraine response in migraine without aura patients. In addition, findings from brain imaging studies have demonstrated neuronal and vascular changes in migraine patients both ictally and interictally after PACAP38 infusion.
Human migraine models have shed light on the importance of PACAP38 in the pathophysiology of primary headaches. These studies have also pointed to the PAC receptor and the PACAP38 molecule itself as target sites for drug testing. Future research should seek to understand the mechanisms underlying PACAP38-induced migraine. The results from an ongoing proof of concept randomized clinical trial may reveal the therapeutic potential of anti-PAC receptor antibodies for migraine prevention.
本文旨在回顾 PACAP38 在原发性头痛的人类模型中的作用，讨论 PACAP38 诱导偏头痛的可能机制，并概述未来的研究方向。
实验研究已经证实 PACAP38 是偏头痛样发作的一种有效的药理学“触发”分子。这些研究还揭示了无先兆偏头痛患者 PACAP38 偏头痛反应的异质性。此外，脑成像研究的结果表明，PACAP38 输注后，偏头痛患者在发作期和发作间期均存在神经元和血管变化。
人类偏头痛模型阐明了 PACAP38 在原发性头痛发病机制中的重要性。这些研究还指出 PAC 受体和 PACAP38 分子本身是药物测试的靶点。未来的研究应致力于理解 PACAP38 诱导偏头痛的机制。正在进行的概念验证随机临床试验的结果可能揭示抗 PAC 受体抗体预防偏头痛的治疗潜力。
