Shared and independent roles of CGRP and PACAP in migraine pathophysiology.
Shared and independent roles of CGRP and PACAP in migraine pathophysiology.
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DOI：
10.1186/s10194-023-01569-2
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发表时间：
2023-04-03
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神经肽降钙素基因相关肽（CGRP）和垂体腺苷酸环化酶激活多肽（PACAP）已成为偏头痛发病机制的介质。两者都是血管扩张肽，当注入人体时会引起偏头痛样发作，当注入啮齿动物时会引起偏头痛样症状。在这篇叙述性综述中，我们比较了这些肽在临床和临床前偏头痛作用中的相似性和差异。一个值得注意的临床差异是PACAP，而不是CGRP，导致患者的先兆样症状。这两种肽被发现在不同的，但重叠的区域相关的偏头痛，最值得注意的是与流行的CGRP在三叉神经节和PACAP在蝶腭神经节。在啮齿类动物中，这两种肽具有相同的活性，包括血管舒张、神经源性炎症和伤害感受。最引人注目的是，CGRP和PACAP在啮齿动物中引起类似的偏头痛样症状，表现为光厌恶和触觉异常性疼痛。然而，这些肽似乎通过独立的机制起作用，可能是通过不同的细胞内信号传导途径。这些信号通路的复杂性被多种CGRP和PACAP受体的存在放大，这可能有助于偏头痛的发病机制。基于这些差异，我们认为PACAP及其受体提供了丰富的靶点，以补充和增强目前基于CGRP的偏头痛治疗。
The neuropeptides calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have emerged as mediators of migraine pathogenesis. Both are vasodilatory peptides that can cause migraine-like attacks when infused into people and migraine-like symptoms when injected into rodents. In this narrative review, we compare the similarities and differences between the peptides in both their clinical and preclinical migraine actions. A notable clinical difference is that PACAP, but not CGRP, causes premonitory-like symptoms in patients. Both peptides are found in distinct, but overlapping areas relevant to migraine, most notably with the prevalence of CGRP in trigeminal ganglia and PACAP in sphenopalatine ganglia. In rodents, the two peptides share activities, including vasodilation, neurogenic inflammation, and nociception. Most strikingly, CGRP and PACAP cause similar migraine-like symptoms in rodents that are manifested as light aversion and tactile allodynia. Yet, the peptides appear to act by independent mechanisms possibly by distinct intracellular signaling pathways. The complexity of these signaling pathways is magnified by the existence of multiple CGRP and PACAP receptors that may contribute to migraine pathogenesis. Based on these differences, we suggest PACAP and its receptors provide a rich set of targets to complement and augment the current CGRP-based migraine therapeutics.
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DOI：
10.1186/s10194-017-0821-3
发表时间：
2017-11-23
期刊：
The journal of headache and pain
影响因子：
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作者：
Ashina H;Guo S;Vollesen ALH;Ashina M
通讯作者：
Ashina M
DOI：
10.1177/0333102420983282
发表时间：
2021-04
期刊：
Cephalalgia : an international journal of headache
影响因子：
--
作者：
Bhakta M;Vuong T;Taura T;Wilson DS;Stratton JR;Mackenzie KD
通讯作者：
Mackenzie KD
偏头痛病理生理学中的K（ATP）通道：偏头痛的新型治疗靶点。
DOI：
10.1186/s10194-017-0800-8
发表时间：
2017-08-23
期刊：
The journal of headache and pain
影响因子：
--
作者：
Al-Karagholi MA;Hansen JM;Severinsen J;Jansen-Olesen I;Ashina M
通讯作者：
Ashina M
影响因子：
48
作者：
Bigal, Marcelo E.;Edvinsson, Lars;Silberstein, Stephen D.
通讯作者：
Silberstein, Stephen D.
影响因子：
14.5
作者：
Al-Karagholi, Mohammad Al-Mahdi;Hansen, Jakob Moller;Ashina, Messoud
通讯作者：
Ashina, Messoud