Cgrp May Play A Causative Role in Migraine

TLDR

CGRP levels rise in jugular venous blood during migraine attacks, but it is unclear whether this elevation is a consequence of migraine or a trigger. In a double‑blind crossover trial, 12 migraine‑without‑aura patients received 20‑minute intravenous infusions of human αCGRP (2 µg min⁻¹) or placebo, with headache intensity scored on a 0–10 scale. αCGRP infusion induced headaches in all participants (median peak score 1 vs 0 for placebo, P < 0.01; median maximum 4 vs 0, P = 0.006) and triggered migraine‑like attacks in three patients, indicating that CGRP can provoke migraine.

Abstract

Calcitonin gene-related peptide (CGRP) has been detected in increased amounts in external jugular venous blood during migraine attacks. However, it is unknown whether this is secondary to migraine or whether CGRP may cause headache. In a double-blind crossover study, the effect of human αCGRP (2 μg/min) or placebo infused intravenously for 20 min was studied in 12 patients suffering from migraine without aura. Headache intensity was scored on a scale from 0 to 10. Two patients were excluded due to severe hypotension and one because she had an infection. In the first hour median peak headache score was 1.0 in the hαCGRP group vs. 0 in the placebo group ( P &lt; 0.01). During the following 11 h all patients experienced headaches after hαCGRP vs. one patient after placebo ( P = 0.0004). The median maximal headache score was 4 after CGRP and 0 after placebo ( P = 0.006). In three patients after hαCGRP, but in no patients after placebo, the delayed headache fulfilled the IHS criteria for migraine without aura. As intravenous administration of hαCGRP causes headache and migraine in migraineurs, our study suggests that the increase in CGRP observed during spontaneous migraine attacks may play a causative role.