Can serum neuropeptide levels help diagnose pediatric migraine? A prospective case-control study

The objective of this study was to examine the serum levels of vasoactive neuropeptides (calcitonin gene-related peptide [CGRP], pituitary adenylate cyclase-activating peptide-38 [PACAP-38], substance P [SP], and vasoactive intestinal peptide [VIP], which have been linked to the pathophysiology of migraine in adults) in pediatric migraine without aura during both pain attacks and pain-free periods and in a control group, with a view of evaluating their diagnostic value in pediatric migraine.

The diagnosis of migraine is based on clinical features described by patients and pediatric patients may not be able to express migraine symptoms as clearly as adults. The fact that objective biological markers of migraine have not yet been fully defined makes diagnosis difficult, especially in children.

This prospective cross-sectional case-control study included 39 children and adolescents (aged 8-18 years) diagnosed with migraine without aura and 40 healthy control children between May 2022 and March 2023. The 39 patients with migraine were evaluated both during the course of their migraine attacks and during periods of pain-free status. Plasma vasoactive peptides were measured using an enzyme-linked immunosorbent assay.

The comparison of serum SP, PACAP-38, and CGRP neuropeptide levels in the 39 patients with migriane during the ictal and interictal periods revealed no significant differences between the two periods. VIP neuropeptide levels in the ictal period (mean [standard deviation, SD] 291.6 [118.5] pg/mL) in the migraine cohort were found to be significantly higher than the levels observed in both the interictal (mean [SD] 263.6 [100.9] pg/mL, p = 0.019) and healthy control groups (mean [SD] 229.7 [109.3] pg/mL, p = 0.018) (p < 0.05). The level of the neuropeptide SP (mean [SD] 150.5 [29] pg/mL) in the interictal period was found to be lower than that observed in the healthy control group (mean [SD] 174.6 [39.4] pg/mL, p = 0.030) (p < 0.05). Furthermore, the CGRP level in the interictal period (mean [SD] 395.6 [197.6] pg/mL) was found to be significantly higher than that observed in the healthy control group (mean [SD] 320.3 [126.6] pg/mL, p = 0.049) (p < 0.05). No significant differences were observed in the levels of the other neuropeptides.

The present study revealed elevated VIP levels during the ictal period and elevated CGRP levels during the interictal period in patients with migraine without aura when compared to controls. In addition, VIP serum levels were significantly higher in the ictal period compared to both the interictal period and healthy controls. The findings of our study lend support to the use of these neuropeptides as biomarkers for migraine. Nevertheless, further studies and standardization are necessary to ascertain the diagnostic value of single or combinations of SP, PACAP-38, VIP, and CGRP neuropeptides in diagnosing pediatric migraine and differentiating pediatric migraine from non-migraine headaches.