Department of Molecular Physiology and Biophysics and Department of Neurology, University of Iowa, Iowa City, IA, 52242, USA.
Veterans Affairs Medical Center, Iowa City, IA, 52246, USA.
J Headache Pain. 2023 Apr 3;24(1):34. doi: 10.1186/s10194-023-01569-2.
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.
降钙素基因相关肽（CGRP）和垂体腺苷酸环化酶激活肽（PACAP）已成为偏头痛发病机制的介质。这两种都是血管扩张肽，如果注入人体，会引起类似偏头痛的发作；如果注入啮齿动物，会引起类似偏头痛的症状。在这篇叙述性综述中，我们比较了这两种肽在偏头痛的临床和临床前作用中的相似和不同之处。一个值得注意的临床差异是，PACAP 会引起患者类似前驱期的症状，但 CGRP 不会。这两种肽在不同但重叠的与偏头痛相关的区域都有发现，尤其是 CGRP 在三叉神经节，PACAP 在蝶腭神经节。在啮齿动物中，这两种肽具有相似的活性，包括血管扩张、神经源性炎症和痛觉过敏。最引人注目的是，CGRP 和 PACAP 在啮齿动物中引起类似偏头痛的症状，表现为畏光和触觉过敏。然而，这些肽似乎通过独立的机制起作用，可能通过不同的细胞内信号通路。这些信号通路的复杂性因存在多种 CGRP 和 PACAP 受体而进一步放大，这些受体可能有助于偏头痛的发病机制。基于这些差异，我们认为 PACAP 及其受体提供了一系列丰富的靶点，以补充和增强基于 CGRP 的偏头痛治疗方法。
