Serum CGRP, VIP, and PACAP usefulness in migraine: a case–control study in chronic migraine patients in real clinical practice

Calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypetide-38 (PACAP-38) have relevant roles in migraine pathophysiology. Their serum levels have been proposed as biomarkers for migraine. Our aim was to assess their diagnostic value in real clinical practice in a cohort of chronic migraine (CM), episodic migraine (EM) and healthy controls (HC). We recruited subjects with CM, EM and HC at two medical centers. Blood samples were drawn under fasting conditions in the interictal period, immediately centrifuged and stored at − 80 ºC. Serum levels were determined by ELISA. Neuropeptide levels, the effect of preventatives, correlations with clinical and demographic variables, and their diagnostic value were studied among clinical categories. 296 age- and sex-matched subjects (101 CM, 98 EM and 97 HC) were included. All three neuropeptide serum levels were higher in CM [median and IQ for CGRP = 18.023 pg/ml (14.4–24.7); VIP = 121.732 pg/ml (48.72–186.72) and PACAP = 204.931 pg/ml (101.08–597.64)] vs EM [CGRP = 14.659 pg/ml (10.29–17.45); VIP = 75.603 pg/ml (28.722–107.10); and PACAP = 94.992 pg/ml (65.77–128.48)] and vs HC [CGRP = 13.988 pg/ml (10.095–17.87); VIP = 84.685 pg/ml (35.32–99.79), and PACAP = 103.142 pg/ml (59.42–123.97)]. Using multinomial modeling, only VIP (OR 1.011, 95% CI 1.003–1.018, p = 0.005) and PACAP (OR 1.003, 95% CI 1.001–1.005, p = 0.002) increased the risk for CM, but not for EM. CGRP did not predict CM or EM. This model could correctly classify only 62/101 (61.38%) of CM, 75/98 (76.53%) of EM, and 5/97 (4.12%) of HC [globally 147/296 (49.8%)]. Individually, PACAP performed the best for classifying clinical categories [global accuracy 150/296 (50.67%)]. In CM, neuropeptide levels were higher in those OnaBT-treated than in no-treated patients. Although interictal serum CGRP and VIP were higher in CM than both EM or HC, their utility to discriminate migraine categories was low. Contrary to other studies, PACAP serum levels were also higher in CM than in EM or HC and had more discriminative capability to distinguish CM from EM and HC. Further investigation is needed for determination technique standardization.