Premonitory and nonheadache symptoms induced by CGRP and PACAP38 in patients with migraine

Migraine attacks are often preceded by premonitory symptoms (PS) that may be triggered pharmacologically. We investigated the incidence of PS after administration of calcitonin gene-related peptide (CGRP) or pituitary adenylate cyclase-activating peptide-38 (PACAP38) in patients with migraine without aura (MO) who reported and did not report migraine-like attacks induced by these pharmacological triggers. In addition, we investigated the association between PS and familial predisposition for migraine. In our study, MO patients received continuous intravenous infusion of α-CGRP (n = 40) and PACAP38 (n = 32) for 20 minutes. Premonitory and nonheadache symptoms were recorded by a self-administered questionnaire. Information on familial predisposition was obtained by telephone interview of first-degree relatives using a validated semistructured questionnaire. Twenty-five of 40 patients (63%) developed a migraine-like attack after CGRP infusion and 23 of 32 patients (72%) developed an attack after PACAP38 infusion. Only 2 patients (9%) with a CGRP-induced migraine-like attack reported PS, whereas 11 patients (48%) reported PS after PACAP38. Patients who developed a migraine-like attack did not report more PS than did patients with no attack after CGRP (P = 0.519) or PACAP38 (P = 0.103). Additionally, we found no difference in PS between patients with familial predisposition of migraine (75%) and patients with no family predisposition (56%) (P = 0.101). In conclusion, CGRP did not induce PS, whereas PACAP38 induced PS in 48% of patients. However, CGRP and PACAP38 did not induce more PS in patients who developed an attack compared with those who did not develop an attack.