Primary trigeminal afferents are the main source for stimulus-induced CGRP release into jugular vein blood and CSF
Primary trigeminal afferents are the main source for stimulus-induced CGRP release into jugular vein blood and CSF
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DOI：
10.1177/0333102412447701
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发表时间：
2012-07-01
期刊：
影响因子：
4.9
通讯作者：
Reuter, Uwe
中科院分区：
文献类型：
--
作者：
Hoffmann, Jan;Wecker, Sascha;Reuter, Uwe
背景：炎性汤(IS)能显著释放降钙素基因相关肽(CGRP)。目前还不清楚IS诱导的CGRP释放是源于三叉神经血管系统的初级神经元还是次级神经元。方法：我们利用大鼠在体脑室内注射IS后，测定CGRP释放到颈外静脉和脑脊液(CSF)的情况。我们还对三叉神经节和脑干(三叉神经尾侧核)进行了聚合酶链式反应(PCR)和免疫组织化学染色。结果：新生辣椒素治疗后，颈外静脉和脑脊液中CGRP的释放均显著减少，但颈静脉血的抑制作用较脑脊液更为明显。基线CGRP水平不受NCT的影响。聚合酶链式反应结果显示，NCT后，三叉神经节CGRP基因表达显著减少，而脑干CGRP基因表达无明显变化。三叉神经节和脑干的免疫组织化学结果支持上述结果。结论：三叉神经切断脑膜后，静息状态的CGRP水平仍可维持。然而，就功能而言，初级三叉神经传入是强制性的，因为它们是刺激诱导的CGRP释放的主要来源。
Background: Administration of inflammatory soup (IS) leads to a significant release of calcitonin gene-related peptide (CGRP). Whether IS-induced CGRP release originates in primary or secondary neurons of the trigeminovascular system has not been clarified.Methods: We determined CGRP release into the external jugular vein and in cerebrospinal fluid (CSF) following intracisternal IS administration using an in vivo rat model. We further performed polymerase chain reaction (PCR) and immunohistochemistry of the trigeminal ganglion and brainstem (trigeminal nucleus caudalis). To further elucidate a primary vs. secondary origin, experiments were repeated after neonatal capsaicin treatment (NCT) as this treatment destroys primary trigeminal afferents.Results: IS-induced CGRP release into the external jugular vein and CSF were significantly reduced after NCT in both compartments but inhibition was more pronounced in jugular vein blood than in CSF. Baseline CGRP levels were not affected by NCT. PCR results show that following NCT, CGRP mRNA was significantly reduced in the trigeminal ganglion but not in the brainstem. Immunohistochemistry of the TG and brainstem support these results.Conclusions: We conclude that resting state CGRP levels can be maintained after trigeminal denervation of the meninges. However, for functional purposes primary trigeminal afferents are mandatory as they are the major source for stimulus-induced CGRP release.