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

TY - JOUR

T1 - Involvement of calcitonin gene-related peptide in migraine

T2 - regional cerebral blood flow and blood flow velocity in migraine patients

AU - Lassen, L H

AU - Jacobsen, V B

AU - Haderslev, P A

AU - Sperling, B

AU - Iversen, Helle Klingenberg

AU - Olesen, J

AU - Tfelt-Hansen, P

PY - 2008/6

Y1 - 2008/6

N2 - 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.

AB - 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.

KW - Adult

KW - Blood Flow Velocity

KW - Blood Pressure

KW - Calcitonin Gene-Related Peptide

KW - Cerebrovascular Circulation

KW - Cross-Over Studies

KW - Double-Blind Method

KW - Female

KW - Heart Rate

KW - Humans

KW - Male

KW - Middle Aged

KW - Middle Cerebral Artery

KW - Migraine Disorders

KW - Multivariate Analysis

KW - Regional Blood Flow

KW - Time Factors

KW - Tomography, Emission-Computed, Single-Photon

KW - Ultrasonography, Doppler, Transcranial

U2 - 10.1007/s10194-008-0036-8

DO - 10.1007/s10194-008-0036-8

M3 - Journal article

C2 - 18437288

SN - 1129-2369

VL - 9

SP - 151

EP - 157

JO - Journal of Headache and Pain

JF - Journal of Headache and Pain

IS - 3

ER -