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

Cephalalgia. 2009 Jan;29(1):23-30. doi: 10.1111/j.1468-2982.2008.01695.x.

Abstract

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 microg 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 (133)Xenon single-photon emission computed tomography, mean blood flow velocity in the middle cerebral artery (V(MCA)) 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 rCBF(MCA), P = 0.38) and the same applied for the V(MCA) (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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin / metabolism*
  • Adrenomedullin / pharmacokinetics*
  • Adult
  • Brain / metabolism
  • Cerebrovascular Circulation / physiology*
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders / metabolism*
  • Ultrasonography, Doppler, Transcranial

Substances

  • Adrenomedullin