Plasma levels of vasoactive neuropeptides in pediatric patients with migraine during attack and attack-free periods

Abstract

Background Increasing evidence suggests that vasoactive neuropeptides such as pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide are involved in the pathophysiology of migraine in adults, but their role in pediatric migraineurs remains unclear. We prospectively investigated plasma levels of these vasoactive neuropeptides in pediatric migraine patients without aura and compared the results with those of age-matched healthy controls. Methods Thirty-eight children aged 6–18 years with migraine without aura and 20 age-matched control subjects were included in the study. Neuropeptides in plasma samples from the controls, and in either the ictal or interictal periods in pediatric migraine without aura, were measured using ELISA. Results PACAP-38 and vasoactive intestinal peptide levels in both ictal and interictal plasma were higher in the patients with pediatric migraine without aura than in the controls ( p < 0.001), although calcitonin gene-related peptide and substance P levels remained unchanged. Otherwise, no significant difference was determined between ictal and interictal periods in terms of all neuropeptide levels. Conclusions This study demonstrates increased plasma PACAP-38 and vasoactive intestinal peptide levels, but not calcitonin gene-related peptide and substance P levels, in pediatric patients with migraine during both attack and attack-free periods. The study findings suggest that PACAP-38 and vasoactive intestinal peptide may be implicated in the pathophysiology of migraine, particularly in pediatric migraineurs.

Determining 5HT7R’s Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine

“…Such repetition of IS-induced development of central sensitization and its consequence, cutaneous hyperalgesia, may arise from hyperexcitability that likely develops in trigeminal nociceptive neurons in response to their repetitive activation ( Figures 2C,E ). The sensitization of trigeminal meningeal nociceptors in migraine is strongly related to meningeal neurogenic inflammation with a cascade of events such as neuropeptides release (e.g., CGRP and SP) ( Hanci et al, 2021 ). CGRP is a potent vasodilator leading to vasodilation in the dura mater during a migraine attack ( Hanko et al, 1985 ; Kilinc et al, 2018 ), while substance P shows a far less potent vasoactive effect compared with CGRP, but it is the prime mediator that regulates plasma protein extravasation secondary to capillary leakage ( Markowitz et al, 1988 ).…”

Pituitary Adenylate Cyclase-Activating Polypeptide: A Potent Therapeutic Agent in Oxidative Stress

“…Unlike the previous nervous system disorders discussed, PACAP is negatively implicated in migraine pathology [99][100][101]. The manifestation of migraines may be correlated with vasodilation [99].…”

“…Notably, it was found that electroacupuncture (EA) treatment significantly decreased concentrations of CGRP, VIP, and PACAP in rat models of recurrent migraines [99]. Clinically, plasma samples from pediatric migraine patients without aura were examined to determine the levels of PACAP and VIP compared to the control [101]. Concentrations of PACAP-38 and VIP were significantly higher in migraine patients than healthy individuals [101].…”

“…Clinically, plasma samples from pediatric migraine patients without aura were examined to determine the levels of PACAP and VIP compared to the control [101]. Concentrations of PACAP-38 and VIP were significantly higher in migraine patients than healthy individuals [101].…”

Characterisation of agonist signalling profiles and agonist‐dependent antagonism at PACAP‐responsive receptors: Implications for drug discovery

“…The role of VIP in migraine is less clear. VIP is capable of inducing a delayed vascular headache in healthy volunteers and circulating VIP is elevated following a spontaneous migraine attack (Hanci et al, 2020;Pellesi et al, 2020). However, in migraine patients, VIP either does not or only weakly, induces a migraine-like attack (Amin et al, 2014;Rahmann et al, 2008).…”