Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

L H Lassen, V B Jacobsen, P A Haderslev, B Sperling, H K Iversen, J Olesen, P Tfelt-Hansen

Abstract

Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment of migraine attacks. It is therefore important to investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (halphaCGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of halphaCGRP (2 mug/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (V (mean)) in the middle cerebral artery (MCA), as well as the heart rate and blood pressure, were the outcome parameters. No change of rCBF was observed at the end of infusion [1.2% +/- 1.7 with halphaCGRP, vs. -1.6% +/- 3.1 with placebo (mean +/- SD)] (P = 0.43). V (mean) in MCA decreased to 13.5% +/- 3.6 with halphaCGRP versus 0.6% +/- 1.8 with placebo (P < 0.005). Since rCBF was unchanged, this indicates a dilation of the MCA. halphaCGRP induced a decrease in MAP (12%) (P < 0.005) and an increase in heart rate (58%) (P < 0.0001). CGRP dilates cerebral arteries, but the effect is so small that it is unlikely to be the only mechanism of CGRP-induced migraine.

Original languageEnglish
JournalJournal of Headache and Pain
Volume9
Issue number3
Pages (from-to)151-7
Number of pages7
ISSN1129-2369
DOIs
Publication statusPublished - Jun 2008
Externally publishedYes

Keywords

  • Adult
  • Blood Flow Velocity/drug effects
  • Blood Pressure/drug effects
  • Calcitonin Gene-Related Peptide/administration & dosage
  • Cerebrovascular Circulation/drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Heart Rate/drug effects
  • Humans
  • Male
  • Middle Aged
  • Middle Cerebral Artery/diagnostic imaging
  • Migraine Disorders/diagnostic imaging
  • Multivariate Analysis
  • Regional Blood Flow/drug effects
  • Time Factors
  • Tomography, Emission-Computed, Single-Photon/methods
  • Ultrasonography, Doppler, Transcranial

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