Hoffmann J, Neeb L, Israel H, Dannenberg F, Triebe F, Dirnagl U, Reuter U
Charité-Universitätsmedizin Berlin, Department of Neurology, 10117 Berlin, Germany.
Cephalalgia. 2009 Nov;29(11):1212-7. doi: 10.1111/j.1468-2982.2009.01858.x. Epub 2009 Apr 9.
The release of calcitonin gene-related peptide (CGRP) and sensitization of the trigeminal nerve system are important elements in migraine pathophysiology. Sensitization can be induced by topical meningeal administration of inflammatory soup (IS). CGRP release is a marker of trigeminal nerve activation. We examined the effect of intracisternal IS administration on CGRP release in rat jugular vein blood at baseline, 2 and 15 min after the beginning of IS infusion. IS administration caused a significant increase of CGRP levels after 2 and 15 min compared with baseline. Daily oral treatment with topiramate for 4 and 8 weeks led to a dose- and time-dependent reduction of IS-induced CGRP release. Sumatriptan also attenuated stimulated neuropeptide release. These results indicate that intracisternal IS administration leads to activation of the trigeminal system. The inhibition of CGRP release by topiramate offers a possible mechanism that may in part account for the preventative antimigraine activity of this drug.
降钙素基因相关肽（CGRP）的释放以及三叉神经系统的致敏作用是偏头痛病理生理学中的重要因素。脑膜局部给予炎症介质混合物（IS）可诱导致敏作用。CGRP释放是三叉神经激活的一个标志。我们检测了在脑池内给予IS后，在基线水平、IS输注开始后2分钟和15分钟时大鼠颈静脉血中CGRP的释放情况。与基线相比，给予IS后2分钟和15分钟时CGRP水平显著升高。每日口服托吡酯4周和8周可导致IS诱导的CGRP释放呈剂量和时间依赖性降低。舒马曲坦也可减弱刺激引起的神经肽释放。这些结果表明，脑池内给予IS可导致三叉神经系统激活。托吡酯对CGRP释放的抑制作用提供了一种可能的机制，这可能部分解释了该药物预防偏头痛的作用。
