Background

Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches.

Objective

The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides.

Methods

In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K⁺ or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of PACAP and calcitonin gene-related peptide receptors and ligands.

Results

Calcitonin gene-related peptide (CGRP) is released from the trigeminal ganglion and dura mater. In contrast, PACAP is only released from the trigeminal ganglion. We observed a weak correlation between the stimulated release of the two neuropeptides. PACAP-38 immunoreactivity was expressed alone and in a subpopulation of neurons in the trigeminal ganglion that also store calcitonin gene-related peptide. The receptor subtype PAC₁ was mainly expressed in the satellite glial cells (SGCs), which envelop the neurons in the trigeminal ganglion, in some neuronal processes, inside the Aδ-fibres and in the outermost layer of the myelin sheath that envelopes the Aδ-fibres.

Conclusion

Unlike CGRP, PACAP is only released within the trigeminal ganglion. This raises the question of whether a migraine therapy aimed at preventing peripheral PACAP signalling would be as successful as the CGRP signalling targeted treatments.

中文翻译：

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三叉神经血管系统垂体腺苷酸环化酶激活肽和降钙素基因相关肽释放的差异。

背景

几种神经递质在三叉神经节的神经元中表达。一种这样的信号分子是垂体腺苷酸环化酶激活肽 (PACAP)。PACAP 信号已被建议在原发性头痛的病理生理学中具有可能的作用。

客观的

本研究旨在研究 PACAP 与降钙素基因相关肽（目前两种最相关的偏头痛肽）之间的关系。

方法

在当前的研究中，我们使用 ELISA 来研究 PACAP 和降钙素基因相关肽的释放，以使用大鼠半颅骨模型响应 60 mM K ⁺或辣椒素。我们将此分析与 qPCR 和免疫组织化学相结合，研究 PACAP 和降钙素基因相关肽受体和配体的表达。

结果

降钙素基因相关肽 (CGRP) 从三叉神经节和硬脑膜释放。相比之下，PACAP 仅从三叉神经节释放。我们观察到两种神经肽的刺激释放之间存在弱相关性。PACAP-38 免疫反应性在三叉神经节的神经元亚群中单独表达，也存储降钙素基因相关肽。受体亚型 PAC ₁主要在卫星神经胶质细胞 (SGC) 中表达，卫星神经胶质细胞包裹着三叉神经节中的神经元，在一些神经元突中，在 Aδ-纤维内部和包裹 Aδ-的髓鞘的最外层。纤维。

结论

与 CGRP 不同，PACAP 仅在三叉神经节内释放。这就提出了一个问题，即旨在预防外周 PACAP 信号传导的偏头痛治疗是否会与 CGRP 信号传导靶向治疗一样成功。