Schoonman, G. G. et al. Migraine headache is not associated with cerebral or meningeal vasodilatation-a 3T magnetic resonance angiography study. Brain 131, 2192-2200

Department of Neurology (K5-Q), Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
Brain (Impact Factor: 9.2). 05/2008; 131(Pt 8):2192-200. DOI: 10.1093/brain/awn094
Source: PubMed


Migraine headache is widely believed to be associated with cerebral or meningeal vasodilatation. Human evidence for this hypothesis is lacking. 3 Tesla magnetic resonance angiography (3T MRA) allows for repetitive, non-invasive, sensitive assessment of intracranial vasodilatation and blood flow. Nitroglycerine (NTG) can faithfully induce migraine attacks facilitating pathophysiological studies in migraine. Migraineurs (n = 32) randomly received NTG (IV 0.5 microg/kg/min for 20 min; n = 27) or placebo (n = 5; for blinding reasons). Using 3T MRA, we measured: (i) blood flow in the basilar (BA) and internal carotid arteries (ICA) and (ii) diameters of the middle meningeal, external carotid, ICA, middle cerebral, BA and posterior cerebral arteries at three timepoints: (a) at baseline, outside an attack; (b) during infusion of NTG or placebo and (c) during a provoked attack or, if no attack had occurred, at 6 h after infusion. Migraine headache was provoked in 20/27 (74%) migraineurs who received NTG, but in none of the five patients who received placebo. The headache occurred between 1.5 h and 5.5 h after infusion and was unilateral in 18/20 (90%) responders. During NTG (but not placebo) infusion, there was a transient 6.7-30.3% vasodilatation (P < 0.01) of all blood vessels. During migraine, blood vessel diameters were no different from baseline, nor between headache and non-headache sides. There were no changes in BA and ICA blood flow during either NTG infusion or migraine. In contrast to widespread belief, migraine attacks are not associated with vasodilatation of cerebral or meningeal blood vessels. Future anti-migraine drugs may not require vasoconstrictor action.

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    • "µm for cortical arterioles and 38±8 µm for cortical venules. After injection of GTN there was a clear vasodilatatory effect on cortical arterioles (n = 6; P<0.05, Figure 2A,B,C) consistent with many previous observations [3], [17], [18], [19], [22]. There was also a clear trend for vasodilation of venules (Figure 2A,D,E) but this effect did not reach the significance (n = 8; P = 0.09). "
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    ABSTRACT: Vascular changes underlying headache in migraine patients induced by Glyceryl trinitrate (GTN) were previously studied with various imaging techniques. Despite the long history of medical and experimental use of GTN, its effects on the brain vasculature are still poorly understood presumably due to low spatial resolution of the imaging modalities used so far. We took advantage of the micrometer-scale vertical resolution of two-photon microscopy to differentiate between the vasodynamic effects of GTN on meningeal versus cortical vessels imaged simultaneously in anesthetized rats through either thinned skull or glass-sealed cranial window. Intermediate and small calibre vessels were visualized in vivo by imaging intravascular fluorescent dextran, and detection of blood flow direction allowed identification of individual arterioles and venules. We found that i.p.-injected GTN induced a transient constriction of meningeal arterioles, while their cortical counterparts were, in contrast, dilated. These opposing effects of GTN were restricted to arterioles, whereas the effects on venules were insignificant. Interestingly, the NO synthase inhibitor L-NAME did not affect the diameter of meningeal vessels but induced a constriction of cortical vessels. The different cellular environment in cortex versus meninges as well as distinct vessel wall anatomical features probably play crucial role in the observed phenomena. These findings highlight differential region- and vessel-type-specific effects of GTN on cranial vessels, and may implicate new vascular mechanisms of NO-mediated primary headaches.
    PLoS ONE 02/2014; 9(2):e89699. DOI:10.1371/journal.pone.0089699 · 3.23 Impact Factor
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    • "A critical assumption in this estimation is that the diameter of the conduit vessel being insonated remains constant across the range of CO 2 levels we tested (e.g., Serrador et al., 2000). However, there is some evidence that larger conduit arteries may change diameter to vasodilatory challenges (e.g., hypercapnia, hypoxia and nitroglycerine; Giller et al., 1993; Hansen et al., 2007; Schoonman et al., 2008; Willie et al., 2012; Wilson et al., 2011). Thus, TCD may underestimate CBF responses in some situations, as velocity will be reduced in the insonated vessel if it is dilated relative to if the vessel remained a constant diameter. "
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    ABSTRACT: The potential differences in cerebrovascular responses between the anterior and posterior circulations in response to changes in CO2 are unclear in humans. Using transcranial Doppler ultrasound, we compared the CO2 reactivity of the (1) BA and PCA and (2) MCA and PCA during hyperoxic rebreathing in supine position. The reactivity in the BA and PCA were similar in both absolute (1.27±0.5 and 1.27±0.6cm/s/Torr; P=0.992) and relative (3.98±1.3 and 3.66±1.5%/Torr CO2; P=0.581) measures, suggesting that the PCA is an adequate surrogate measure of reactivity for the BA. The MCA reactivity was greater than the PCA in absolute (2.09±0.7 and 1.22±0.5cm/s/Torr CO2; P<0.001), but not relative measures (3.25±1.0 and 3.56±1.6%/Torr CO2; P=0.629). Our findings (a) confirm regional differences in the absolute reactivity in the human brain and (b) suggest that in cerebrovascular studies investigating functions mediated by posterior brain structures (e.g., control of breathing), the posterior vasculature should also be insonated.
    Respiratory Physiology & Neurobiology 06/2013; 189(1). DOI:10.1016/j.resp.2013.05.036 · 1.97 Impact Factor
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    • "Successive findings corroborate the release of vasoactive and neuroactive substances like endorphins, serotonin, histamine, adenosine, prostaglandins and nitric oxide in causing neurogenic inflammation.16–18 Various findings19,20 including non-induction of migraine headache by vasodilating substances as vasoactive intestinal peptide (VIP) could not be explained by vasogenic theory. VIP has been found to induce vasodilation of cranial vessels but failure to triggering migraine attack21 supports that vascular changes are not necessary in migraine. "
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    ABSTRACT: Migraine is defined as recurrent attack of headache that are commonly unilateral and accompanied by gastrointestinal and visual disorders. Migraine is more prevalent in females than males with a ratio of 3:1. It is primarily a complex neurovascular disorder involving local vasodilation of intracranial, extracerebral blood vessels and simultaneous stimulation of surrounding trigeminal sensory nervous pain pathway that results in headache. The activation of 'trigeminovascular system' causes release of various vasodilators, especially calcitonin gene-related peptide (CGRP) that induces pain response. At the same time, decreased levels of neurotransmitter, serotonin have been observed in migraineurs. Serotonin receptors have been found on the trigeminal nerve and cranial vessels and their agonists especially triptans prove effective in migraine treatment. It has been found that triptans act on trigeminovascular system and bring the elevated serum levels of key molecules like calcitonin gene related peptide (CGRP) to normal. Currently CGRP receptor antagonists, olcegepant and telcagepant are under consideration for antimigraine therapeutics. It has been observed that varying levels of ovarian hormones especially estrogen influence serotonin neurotransmission system and CGRP levels making women more predisposed to migraine attacks. This review provides comprehensive information about the role of serotonin and CGRP in migraine, specifically the menstrual migraine.
    Annals of Neurosciences 04/2012; 19(2):88-94. DOI:10.5214/ans.0972.7531.12190210
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