To determine total pituitary adenylate cyclase activating polypeptide (PACAP) in peripheral blood as a potential marker of the activation of the parasympathetic arm of the trigemino‐vascular system in chronic migraine (CM) in a case‐control study.

Women older than 17 and diagnosed as CM were recruited. Healthy women with no headache history and women with episodic migraine (EM) served as control groups. Total PACAP and vasoactive intestinal peptide (VIP) levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack and having taken no symptomatic medication the day before.

We assessed serum samples from 86 women with CM, 32 healthy women, and 35 women with EM. There were no differences in PACAP levels in CM patients (109.8 ± 43.8, 97.4 [32.5–253.1] pg/mL), controls (108.7 ± 43.0, 98.7 [50.7–197.3] pg/mL), or EM patients (98.8 ± 34.3, 94.2 [52.0–190.7] pg/mL). VIP levels were significantly increased (P = .027) in CM as compared to control healthy women (136.0 ± 111.5 pg/mL; 103.1 [20.5–534.0] pg/mL vs 88.6 ± 61.0 pg/mL; 66.0 [21.1–256.1]) and EM patients (103.0 ± 56.7 pg/mL; 103.5 [15.2–263.0] pg/mL). In the range of this study variables such as age, CM duration, the presence of aura, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption or kind of preventative treatment did not significantly influence PACAP or VIP levels.

In contrast to VIP, interictal PACAP level measured in peripheral blood does not seem to be a biomarker reflecting parasympathetic activation in CM.