Schlereth Tanja, Schukraft Jonas, Krämer-Best Heidrun H, Geber Christian, Ackermann Tatiana, Birklein Frank
Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, D-55131 Mainz, Germany.
Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, D-55131 Mainz, Germany.
Neuropeptides. 2016 Oct;59:57-62. doi: 10.1016/j.npep.2016.06.001. Epub 2016 Jun 18.
Calcitonin gene related peptide (CGRP) and substance P (SP) are neuropeptides that are simultaneously released from nociceptive C-fibers. CGRP is a potent vasodilator, inducing a long-lasting increase in superficial skin blood flow, whereas SP induces only a brief vasodilation but a significant plasma extravasation. CGRP and SP may play important roles in the pathophysiology of various pain states but little is known about their interaction. Different concentrations of SP (ranging from 10M to 10M) were applied to the volar forearm of 24 healthy subjects via dermal microdialysis. SP was applied either alone or in combination with CGRP10M and CGRP 10M. As expected, SP induced a transient increase in skin blood flow that decayed shortly after application. This transient blood flow peak was blunted with co-application of CGRP 10M and inhibited with co-application of CGRP10M. SP alone induced plasma protein extravasation (PPE). However, when CGRP10M was added, the PPE significantly increased. Our results demonstrate a complex interaction of the neuropeptides CGRP and SP. CGRP10M prevented SP-induced early vasodilation but augmented SP-induced PPE. These interactions might explain why vascular symptoms in chronic pain can differ strikingly between individuals.
降钙素基因相关肽(CGRP)和P物质(SP)是从伤害性C纤维同时释放的神经肽。CGRP是一种强效血管舒张剂,可使浅表皮肤血流持久增加,而SP仅诱导短暂的血管舒张,但会引起明显的血浆外渗。CGRP和SP可能在各种疼痛状态的病理生理学中起重要作用,但对它们之间的相互作用知之甚少。通过皮肤微透析将不同浓度的SP(范围从10M至10M)应用于24名健康受试者的掌侧前臂。SP单独应用或与10M CGRP和10M CGRP联合应用。正如预期的那样,SP诱导皮肤血流短暂增加,在应用后不久即衰减。这种短暂的血流峰值在与10M CGRP联合应用时减弱,在与10M CGRP联合应用时受到抑制。单独使用SP可诱导血浆蛋白外渗(PPE)。然而,当加入10M CGRP时,PPE显著增加。我们的结果表明神经肽CGRP和SP之间存在复杂的相互作用。10M CGRP可预防SP诱导的早期血管舒张,但增强SP诱导的PPE。这些相互作用可能解释了为什么慢性疼痛中的血管症状在个体之间可能有显著差异。