Substance P release from rat dura mater is inversely correlated with CGRP release- experiments using glycerol trinitrate and anti-CGRP antibodies.

IF 7.3 1区医学 Q1 CLINICAL NEUROLOGY

Journal of Headache and Pain Pub Date : 2025-05-16 DOI:10.1186/s10194-025-02050-y

Mária Dux, Karl Messlinger

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Abstract

Background: The neuropeptides calcitonin gene-related peptide (CGRP) and substance P are important mediators of neurogenic inflammation when they are released from activated primary nociceptive afferents. It is long evident that neuropeptides play an important role in migraine pathophysiology, but the significance of neurogenic inflammation is still debated.

Methods: In an approved hemisected rodent head preparation, we measured CGRP release from the cranial dura mater in parallel with substance P release using animals pre-treated with anti-CGRP antibodies or control solutions.

Results: Apart from the known decrease in CGRP release following antibody treatment, we found a significant inverse correlation of basal and stimulated CGRP versus substance P release across all experiments. The results are discussed in connection with our previously published data.

Conclusions: An increase in CGRP release seems to inhibit substance P release in meningeal structures possibly decreasing substance P-dependent plasma extravasation, which argues against a significant role of neurogenic inflammation in migraine.

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大鼠硬脑膜P物质释放与CGRP释放呈负相关——使用三硝酸甘油和抗CGRP抗体的实验。

背景：降钙素基因相关肽（CGRP）和P物质是神经源性炎症的重要介质，当它们从激活的初级伤害感受事件释放出来时。神经肽在偏头痛的病理生理中起着重要的作用是显而易见的，但神经源性炎症的意义仍然存在争议。方法：在一种被批准的半切啮齿动物头部制备中，我们用抗CGRP抗体或对照溶液预处理动物，测量了CGRP从颅硬脑膜释放的同时，也测量了P物质的释放。结果：除了已知的抗体治疗后CGRP释放减少外，我们发现在所有实验中，基础和刺激的CGRP与P物质释放呈显著的负相关。这些结果将与我们以前发表的数据联系起来讨论。结论：CGRP释放的增加似乎抑制脑膜结构中P物质的释放，可能减少P物质依赖性血浆外溢，这反驳了偏头痛中神经源性炎症的重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Headache and Pain 医学-临床神经学

CiteScore

11.80

自引率

13.50%

发文量

143

审稿时长

6-12 weeks

期刊介绍： The Journal of Headache and Pain, a peer-reviewed open-access journal published under the BMC brand, a part of Springer Nature, is dedicated to researchers engaged in all facets of headache and related pain syndromes. It encompasses epidemiology, public health, basic science, translational medicine, clinical trials, and real-world data. With a multidisciplinary approach, The Journal of Headache and Pain addresses headache medicine and related pain syndromes across all medical disciplines. It particularly encourages submissions in clinical, translational, and basic science fields, focusing on pain management, genetics, neurology, and internal medicine. The journal publishes research articles, reviews, letters to the Editor, as well as consensus articles and guidelines, aimed at promoting best practices in managing patients with headaches and related pain.