Adrenomedullin induces migraine-like attacks in patients with migraine without aura

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.