Feistel Stephan, Albrecht Stephanie, Messlinger Karl
J Headache Pain. 2013 Nov 20;14(1):93. doi: 10.1186/1129-2377-14-93.
Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches. Migraineurs respond to infusion of nitroglycerin with delayed headaches, and inhibition of CGRP receptors has been shown to be effective in migraine therapy. In animal experiments nitrovasodilators like nitroglycerin induced increases in spinal trigeminal activity, which were reversed after inhibition of CGRP receptors. In the present study we asked if CGRP receptor inhibition can also prevent spinal trigeminal activity induced by nitroglycerin.
In isoflurane anaesthetised rats extracellular recordings were made from neurons in the spinal trigeminal nucleus with meningeal afferent input. The non-peptide CGRP receptor inhibitor MK-8825 (5 mg/kg) dissolved in acidic saline (pH 3.3) was slowly infused into rats one hour prior to prolonged glyceryl trinitrate (nitroglycerin) infusion (250 μg/kg/h for two hours).
After infusion of MK-8825 the activity of spinal trigeminal neurons with meningeal afferent input did not increase under continuous nitroglycerin infusion but decreased two hours later below baseline. In contrast, vehicle infusion followed by nitroglycerin was accompanied by a transient increase in activity.
CGRP receptors may be important in an early phase of nitroglycerin-induced central trigeminal activity. This finding may be relevant for nitroglycerin-induced headaches.
降钙素基因相关肽（CGRP）和一氧化氮（NO）被认为是偏头痛及其他原发性头痛的关键介质。偏头痛患者对硝酸甘油输注会出现延迟性头痛反应，且抑制CGRP受体已被证明在偏头痛治疗中有效。在动物实验中，像硝酸甘油这样的硝基血管扩张剂会导致三叉神经脊髓核活动增加，而在抑制CGRP受体后这种增加会逆转。在本研究中，我们探究了抑制CGRP受体是否也能预防硝酸甘油诱导的三叉神经脊髓核活动。
在异氟烷麻醉的大鼠中，对具有脑膜传入输入的三叉神经脊髓核中的神经元进行细胞外记录。将溶解于酸性生理盐水（pH 3.3）中的非肽类CGRP受体抑制剂MK-8825（5 mg/kg）在长时间输注硝酸甘油（250 μg/kg/h，持续两小时）前一小时缓慢注入大鼠体内。
注入MK-8825后，在持续输注硝酸甘油的情况下，具有脑膜传入输入的三叉神经脊髓核神经元活动并未增加，但两小时后降至基线以下。相比之下，先注入赋形剂再输注硝酸甘油会伴随着活动的短暂增加。
CGRP受体可能在硝酸甘油诱导的中枢三叉神经活动的早期阶段起重要作用。这一发现可能与硝酸甘油诱导的头痛有关。
