PACAP and its role in primary headaches.
PACAP and its role in primary headaches.
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DOI：
10.1186/s10194-018-0852-4
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发表时间：
2018-03-09
期刊：
影响因子：
--
通讯作者：
Vécsei L
中科院分区：
文献类型：
--
作者：
Edvinsson L;Tajti J;Szalárdy L;Vécsei L
脑垂体腺苷环化酶激活肽(PACAP)是一种神经肽，参与多种功能，如伤害性感受和原发性头痛。关于PACAP的定位，已在三叉神经节(TG)、副交感蝶腭神经节(SPG)和耳神经节(OTG)以及脑干三叉神经颈复合体中观察到。免疫组织化学显示PACAP-38存在于SPG/OTG的大量胞体中，与血管活性肠肽(VIP)、一氧化氮合酶(NOS)共储存，少量与胆碱乙酰转移酶共储存。此外，在三叉神经系统的降钙素基因相关肽(CGRP)免疫反应细胞亚群中也发现了PACAP。PACAP/VIP受体(PAC1、VPAC1和VPAC2)存在于感觉神经元和与三叉神经血管系统相关的血管平滑肌中。据推测，PACAP参与了伤害性感受。在支持方面，PACAP合成或接收的取消会导致疼痛反应减弱，而全身注射PACAP-38会触发动物的疼痛行为，并在没有明显血管扩张作用的偏头痛患者中延迟偏头痛样发作。此外，根据三叉神经激活实验模型的研究结果，在急性偏头痛发作和丛集性头痛中，血浆水平也有升高的记录。这表明三叉神经系统的激活可能导致静脉中PACAP水平的升高，这种变化在头痛治疗后可以减少。这篇综述中的数据表明，PACAP及其受体可能是偏头痛治疗的有希望的靶点。
Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide implicated in a wide range of functions, such as nociception and in primary headaches. Regarding its localization, PACAP has been observed in the sensory trigeminal ganglion (TG), in the parasympathetic sphenopalatine (SPG) and otic ganglia (OTG), and in the brainstem trigeminocervical complex. Immunohistochemistry has shown PACAP-38 in numerous cell bodies of SPG/OTG, co-stored with vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS) and, to a minor degree, with choline acetyltransferase. PACAP has in addition been found in a subpopulation of calcitonin gene-related peptide (CGRP)-immunoreactive cells in the trigeminal system. The PACAP/VIP receptors (PAC1, VPAC1, and VPAC2) are present in sensory neurons and in vascular smooth muscle related to the trigeminovascular system. It is postulated that PACAP is involved in nociception. In support, abolishment of PACAP synthesis or reception leads to diminished pain responses, whereas systemic PACAP-38 infusion triggers pain behavior in animals and delayed migraine-like attacks in migraine patients without marked vasodilatory effects. In addition, increased plasma levels have been documented in acute migraine attacks and in cluster headache, in accordance with findings in experimental models of trigeminal activation. This suggest that the activation of the trigeminal system may result in elevated venous levels of PACAP, a change that can be reduced when headache is treated. The data presented in this review indicate that PACAP and its receptors may be promising targets for migraine therapeutics.
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