Department of Pediatrics, Qilu Hospital of Shandong University, No.107 West Wenhua Road, Jinan, 250012, Shandong Province, China.
J Headache Pain. 2022 Jun 13;23(1):68. doi: 10.1186/s10194-022-01435-7.
An increasing number of studies have suggested that the important role of vasoactive peptides, such as pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) and calcitonin gene-related peptide (CGRP), in the pathophysiology of migraine seems undeniable in adults, but studies in pediatric migraine patients remain scarce. We prospectively investigated CGRP and PACAP-38 plasma levels in children with migraine during ictal and interictal periods and compared the results between migraine patients with aura and without aura. We were the first to explore the diagnostic value of a combination of CGRP and PACAP-38.
Seventy-six migraine patients aged 4-18 years and seventy-seven age-matched healthy children were included in the study. Plasma vasoactive peptides were measured using the enzyme-linked immunosorbent assay (ELISA). Differences and correlations of groups were analyzed using the independent samples t-test, analysis of variance (ANOVA), Mann-Whitney U test, and multiple linear regression. We also performed logistic regression and receiver operating characteristic curve (ROC) analyses to evaluate the diagnostic value of CGRP and PACAP-38 in pediatric migraine.
PACAP-38 and CGRP levels in migraine patients during the ictal and interictal periods were higher than those in controls (p < 0.001). PACAP-38 and CGRP levels in migraine patients with aura and without aura were higher than those in controls (p < 0.001). PACAP-38 and CGRP were independent risk factors in diagnosing pediatric migraine (adjusted OR (PACAP-38) =1.331, 95% CI: 1.177-1.506, p < 0.001; adjusted OR (CGRP) = 1.113, 95% CI: 1.064-1.165, p < 0.001). Area Under Curve (AUC) comparison: Combination (0.926) > CGRP (0.869) > PACAP-38 (0.867).
Our study found almost the same changes in CGRP and PACAP levels in pediatric migraine, suggesting that CGRP and PACAP-38 may work together to play an integral role in pediatric migraine. Higher CGRP levels were found in the ictal phase than in the interictal phase and with aura group than without aura group, indicating that CGRP may take part in the formation of pain and aura. Moreover, ROC and logistic regression analyses suggested that CGRP and PACAP-38 are good indicators to diagnose pediatric migraine, and the combination of CGRP and PACAP-38 was valuable in diagnosing pediatric migraine and differentiating pediatric migraine from non-migraine headaches.
The study has been registered at the Chinese Clinical Trial Registry ( ChiCTR2100043157 ).
越来越多的研究表明，血管活性肽（如垂体腺苷酸环化酶激活肽-38（PACAP-38）和降钙素基因相关肽（CGRP））在偏头痛的病理生理学中起着重要作用，这在成人中似乎是不可否认的，但儿科偏头痛患者的研究仍然很少。我们前瞻性地研究了偏头痛发作期和发作间期儿童的 CGRP 和 PACAP-38 血浆水平，并比较了有先兆和无先兆偏头痛患者之间的结果。我们是第一个探索 CGRP 和 PACAP-38 联合的诊断价值的。
本研究纳入了 76 名 4-18 岁的偏头痛患者和 77 名年龄匹配的健康儿童。采用酶联免疫吸附试验（ELISA）检测血管活性肽。采用独立样本 t 检验、方差分析（ANOVA）、Mann-Whitney U 检验和多元线性回归分析组间差异和相关性。我们还进行了逻辑回归和受试者工作特征曲线（ROC）分析，以评估 CGRP 和 PACAP-38 在儿科偏头痛中的诊断价值。
偏头痛患者发作期和发作间期的 PACAP-38 和 CGRP 水平高于对照组（p<0.001）。有先兆和无先兆偏头痛患者的 PACAP-38 和 CGRP 水平均高于对照组（p<0.001）。PACAP-38 和 CGRP 是诊断儿科偏头痛的独立危险因素（调整后的优势比（PACAP-38）=1.331，95%置信区间：1.177-1.506，p<0.001；调整后的优势比（CGRP）=1.113，95%置信区间：1.064-1.165，p<0.001）。曲线下面积（AUC）比较：联合（0.926）>CGRP（0.869）>PACAP-38（0.867）。
本研究发现儿科偏头痛患者 CGRP 和 PACAP 水平几乎相同，提示 CGRP 和 PACAP-38 可能共同发挥作用，在儿科偏头痛中发挥整体作用。在发作期比在发作间期和有先兆组比无先兆组发现 CGRP 水平更高，表明 CGRP 可能参与疼痛和先兆的形成。此外，ROC 和逻辑回归分析表明，CGRP 和 PACAP-38 是诊断儿科偏头痛的良好指标，CGRP 和 PACAP-38 的联合对诊断儿科偏头痛和区分儿科偏头痛与非偏头痛性头痛具有重要价值。
本研究已在中国临床试验注册中心（ChiCTR2100043157）注册。
