Effect of adrenomedullin on the cerebral circulation: relevance to primary headache disorders


Kenneth A. Petersen, MD, PhD, Danish Headache Centre, University Hospital of Copenhagen and Department of Neurology, Glostrup University Hospital, DK-2600 Glostrup, Denmark. Tel. + 45 3810-0448, e-mail kapetersen@dadlnet.dk


Adrenomedullin (ADM) is closely related to calcitonin gene-related peptide, which has a known causative role in migraine. Animal studies have strongly suggested that ADM has a vasodilatory effect within the cerebral circulation. For these reasons, ADM is also likely to be involved in migraine. However, the hypothetical migraine-inducing property and effect on human cerebral circulation of ADM have not previously been investigated. Human ADM (0.08 µg kg−1 min−1) or placebo (saline 0.9%) was administered as a 20-min intravenous infusion to 12 patients suffering from migraine without aura in a crossover double-blind study. The occurrence of headache and associated symptoms were registered regularly 24 h post infusion. Cerebral blood flow (CBF) was measured by 133Xenon single-photon emission computed tomography, mean blood flow velocity in the middle cerebral artery (VMCA) by transcranial Doppler and the diameter of peripheral arteries by transdermal ultrasound (C-scan). ADM did not induce significantly more headache or migraine compared with placebo (P = 0.58). CBF was unaffected by ADM infusion (global CBF, P = 0.32 and rCBFMCA, P = 0.38) and the same applied for the VMCA (P = 0.18). The superficial temporal artery dilated compared with placebo (P < 0.001), and facial flushing was seen after ADM administration (P = 0.001). In conclusion, intravenous ADM is not a mediator of migraine headache and does not dilate intracranial arteries.