Objective: To determine whether the intravenous infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients.

Methods: We have enlisted twenty migraine without aura patients to participate in a placebo-controlled and double-blinded clinical study. In a randomized and crossover design the patients received an intravenous infusion of human adrenomedullin (19.9 picomole/kg/min) or placebo (saline) administrated via an automated intravenous pump for period of (20 minutes). The patients participated in two study days with washout period of minimum of seven days. The main outcome of the study was predefined as a difference in migraine incidence (0–12 h).

Results: Eleven migraine without aura patients (55%) fulfilled migraine attacks criteria after adrenomedullin infusion in comparison to only three patients reported attack (15%) after placebo (P= 0.039). We found that patients reported in a period of (0-12 hours) stronger headache intensity after adrenomedullin in comparison to placebo infusion (P= 0.035).

Conclusion: Our data implicate adrenomedullin in migraine pathogenesis. This suggests that adrenomedullin and/or its receptors are novel therapeutic targets for the treatment of migraine. However, we cannot discount for the possibility that adrenomedullin may be acting through the canonical CGRP receptor.