Tvedskov Jesper Filtenborg, Lipka Kerstin, Ashina Messoud, Iversen Helle K, Schifter Søren, Olesen Jes
Danish Headache Center, University of Copenhagen and Department of Neurology, Glostrup University Hospital, Glostrup, Copenhagen, Denmark.
Ann Neurol. 2005 Oct;58(4):561-8. doi: 10.1002/ana.20605.
Increased calcitonin gene-related peptide (CGRP) in external jugular venous blood during migraine attack is one of the most cited findings in the headache literature. The finding has not been convincingly reproduced and is based on comparison with historic control subjects. The validity of this finding is important for the understanding of migraine. We therefore investigated the issue using an intrapatient comparison design and two different CGRP assays. We sampled blood from the external jugular and cubital vein during, as well as outside of, an attack of migraine without aura. We succeeded in 17 patients, whereas only cubital fossa blood could be sampled in an additional 4 patients. CGRP was measured with the same assay as most previous studies (assay I) and furthermore with a more sensitive and validated assay (assay II). For assay I, mean CGRP concentration in external jugular venous blood during attack was 17.18 pmol/L compared with 15.88 pmol/L outside of attack. Mean difference was 1.81 pmol/L (95% confidence interval [CI]: -2.88, 6.41; p = 0.44). In peripheral blood during attack, CGRP was 16.86 pmol/L compared with 17.57 pmol/L outside of attack. Mean difference was -0.79 pmol/L (95% CI: -4.64, 3.06; p = 0.69). For assay II, external jugular venous blood concentration of CGRP during attack was 32.59 pmol/L compared with 30.59 pmol/L outside of attack; mean difference was 2.00 pmol/L (standard error, 2.39; 95% CI: -3.07, 7.07; p = 0.416). In peripheral blood during attack, CGRP was 33.37 pmol/L compared with 31.84 pmol/L outside of attack; mean difference was 1.53 pmol/L (standard error, 1.90; 95% CI: -2.46, 5.51; p = 0.431). Thus, no difference between CGRP level in external jugular or cubital fossa blood during and outside of attack was found. No difference was found between external jugular and peripheral venous blood. Thus, previous findings of increased CGRP level in external jugular or cubital fossa venous blood could not be confirmed. Our finding strongly suggests that CGRP is not increased in jugular venous blood during migraine without aura. CGRP cannot be used as a biomarker to validate human or animal models of migraine.
偏头痛发作时颈外静脉血中降钙素基因相关肽（CGRP）升高是头痛文献中被引用最多的发现之一。这一发现尚未得到令人信服的重复验证，且是基于与历史对照受试者的比较。这一发现的有效性对于理解偏头痛很重要。因此，我们采用患者自身对照设计和两种不同的CGRP检测方法对该问题进行了研究。我们在无先兆偏头痛发作期间及发作之外，从颈外静脉和肘静脉采集血液样本。我们成功采集到了17例患者的样本，另外4例患者仅能采集到肘窝血液样本。我们使用了与大多数先前研究相同的检测方法（检测方法I）来测量CGRP，此外还使用了一种更灵敏且经过验证的检测方法（检测方法II）。对于检测方法I，发作期间颈外静脉血中CGRP的平均浓度为17.18 pmol/L，发作之外为15.88 pmol/L。平均差异为1.81 pmol/L（95%置信区间[CI]：-2.88，6.41；p = 0.44）。发作期间外周血中CGRP为16.86 pmol/L，发作之外为17.57 pmol/L。平均差异为-0.79 pmol/L（95% CI：-4.64，3.06；p = 0.69）。对于检测方法II，发作期间颈外静脉血中CGRP的浓度为32.59 pmol/L，发作之外为30.59 pmol/L；平均差异为2.00 pmol/L（标准误，2.39；95% CI：-3.07，7.07；p = 0.416）。发作期间外周血中CGRP为33.37 pmol/L，发作之外为31.84 pmol/L。平均差异为1.53 pmol/L（标准误，1.90；95% CI：-2.46，5.51；p = 0.431）。因此，未发现发作期间和发作之外颈外静脉或肘窝血液中CGRP水平存在差异。颈外静脉血和外周静脉血之间也未发现差异。因此，先前关于颈外静脉或肘窝静脉血中CGRP水平升高的发现未能得到证实。我们的发现强烈表明，无先兆偏头痛发作期间颈静脉血中CGRP并未升高。CGRP不能用作验证偏头痛人类或动物模型的生物标志物。
