Comparative Analysis of CGRP, VIP and 
PACAP-38 Levels in Migraine with and 
Without Aura: A Case-control Study.

BACKGROUND

Migraine pathophysiology involves the release of vasoactive neuropeptides following trigeminovascular system activation. While calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) have been individually studied in migraine, their combined role in differentiating migraine subtypes remains unclear.

PURPOSE: The aim of this study was to evaluate serum levels of CGRP, VIP and PACAP-38 in patients with migraine with aura (MA) and without aura (MO) compared to healthy controls (HC), and assess their potential as diagnostic biomarkers.

METHODS

This case-control study included 296 participants (266 females, 30 males) divided into three groups: MA (n = 101), MO (n = 98) and HC (n = 97). Serum neuropeptide levels were measured using enzyme-linked immunosorbent assay (ELISA) under standardised conditions. Clinical characteristics were assessed using attack frequency and Headache Impact Test-6 (HIT-6) scores.

RESULTS

All three neuropeptides were significantly elevated in migraine patients compared to controls (p < .001). CGRP levels were highest in MA (45.6 ± 8.2 pg/mL), followed by MO (38.4 ± 7.8 pg/mL) and HC (28.3 ± 6.4 pg/mL). Similar patterns were observed for VIP (MA: 186.4 ± 24.6, MO: 165.8 ± 22.4, HC: 142.3 ± 20.8 pg/mL) and PACAP-38 (MA: 248.6 ± 32.4, MO: 228.5 ± 30.6, HC: 195.4 ± 28.2 pg/mL). MA patients showed marginally higher attack frequency (4.8 ± 2.3 vs. 4.2 ± 2.1 per month, p = .06) and HIT-6 scores (64.8 ± 6.2 vs 62.4 ± 5.8, p = .08) compared to MO patients.

CONCLUSION

The significant elevation of all three neuropeptides, particularly in MA patients, suggests their potential utility as biomarkers for migraine diagnosis and subtype differentiation. These findings support the neurogenic inflammation hypothesis in migraine pathophysiology and may have implications for targeted therapeutic approaches.