Altered neurovascular coupling in migraineurs could be a consequence of impaired function of modulatory brainstem nuclei. The cold pressor test (CPT) should activate brainstem structures. We measured visually evoked cerebral blood flow velocity response (VEFR) to CPT in migraine.
Methods
Twenty-three healthy volunteers and 29 migraineurs participated in the study. We measured arterial blood pressure, end-tidal CO2, heart rate and cerebral blood flow velocity in posterior and middle cerebral artery using transcranial Doppler. VEFR was calculated as cerebrovascular reactivity to photic stimulation before, during and after CPT.
Results
In healthy individuals, there was a significant decrease in peak systolic VEFR from CPT phase to recovery phase (p < 0.05). There was an increase in mean VEFR from basal to CPT phase and a decrease from CPT to recovery phase, both significant (p < 0.05). End-diastolic VEFR increased from basal to CPT phase and decreased in recovery phase below the basal phase values, all changes significant (p < 0.05). In migraine, no statistically significant changes in peak systolic, mean or end-diastolic VEFRs were observed between phases (p > 0.05). The differences in phases in mean and end-diastolic VEFRs between the basal phase and the CPT phase and between the CPT phase and the recovery phase were significantly higher in healthy individuals (p < 0.05).
Conclusions
The absence of the effect of CPT on VEFR in migraine is likely to be a consequence of impaired subcortical modulation of neurovascular coupling.
NosedaRBursteinR. Migraine pathophysiology: Anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain2013; 154(Suppl 1): S44–S53.
2.
KruitMCvan BuchemMALaunerLJ. Migraine is associated with an increased risk of deep white matter lesions, subclinical posterior circulation infarcts and brain iron accumulation: The population-based MRI CAMERA study. Cephalalgia2010; 30: 129–136.
3.
KurthTChabriatHBousserMG. Migraine and stroke: A complex association with clinical implications. Lancet Neurol2012; 11: 92–100.
4.
MurinovaNKrashinDLLucasS. Vascular risk in migraineurs: Interaction of endothelial and cortical excitability factors. Headache2014; 54: 583–590.
5.
ArkinkEBBleekerEJSchmitzN. Cerebral perfusion changes in migraineurs: A voxelwise comparison of interictal dynamic susceptibility contrast MRI measurements. Cephalalgia2012; 32: 279–288.
6.
MalekiNBecerraLBrawnJ. Concurrent functional and structural cortical alterations in migraine. Cephalalgia2012; 32: 607–620.
7.
ZaletelMStruclMBajrovićFF. Coupling between visual evoked cerebral blood flow velocity responses and visual evoked potentials in migraneurs. Cephalalgia2005; 25: 567–574.
8.
HamelE. Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol (1985)2006; 100: 1059–1064.
9.
AkermanSHollandPRGoadsbyPJ. Diencephalic and brainstem mechanisms in migraine. Nat Rev Neurosci2011; 12: 570–584.
10.
Jeffrey-GauthierRGuillemotJPPichéM. Neurovascular coupling during nociceptive processing in the primary somatosensory cortex of the rat. Pain2013; 154: 1434–1441.
11.
PetrovicPPeterssonKMHanssonP. Brainstem involvement in the initial response to pain. Neuroimage2004; 22: 995–1005.
12.
FabjanAMusizzaBBajrovićFF. The effect of the cold pressor test on a visually evoked cerebral blood flow velocity response. Ultrasound Med Biol2012; 38: 13–20.
13.
The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004; 24 (Suppl 1): 9–160.
14.
AaslidRCerebral hemodynamics. In: NewellDWAaslidR (eds). Transcranial Doppler, New York: Raven Press, 1992, pp. 53–55.
15.
NedeltchevKArnoldMSchwerzmannM. Cerebrovascular response to repetitive visual stimulation in interictal migraine with aura. Cephalalgia2004; 24: 700–706.
16.
WolfMEJagerTBaznerH. Changes in functional vasomotor reactivity in migraine with aura. Cephalalgia2009; 29: 1156–1164.
17.
BrigoFStortiMTezzonF. Primary visual cortex excitability in migraine: A systematic review with meta-analysis. Neurol Sci2013; 34: 819–830.
18.
ChenWTLinYYFuhJL. Sustained visual cortex hyperexcitability in migraine with persistent visual aura. Brain2011; 134(Pt 8): 2387–2395.
19.
ShibataKOsawaMIwataM. Pattern reversal visual evoked potentials in migraine with aura and migraine aura without headache. Cephalalgia1998; 18: 319–323.
BednarMKubovaZKremlacekJ. Lack of visual evoked potentials amplitude decrement during prolonged reversal and motion stimulation in migraineurs. Clin Neurophysiol2014; 125: 1223–1230.
22.
AfraJProietti CecchiniASandorPS. Comparison of visual and auditory evoked cortical potentials in migraine patients between attacks. Clin Neurophysiol2000; 111: 1124–1129.
23.
CoppolaGCurraASerraoM. Lack of cold pressor test-induced effect on visual-evoked potentials in migraine. J Headache Pain2010; 11: 115–121.
24.
CoppolaGPierelliFSchoenenJ. Habituation and migraine. Neurobiol Learn Mem2009; 92: 249–259.
25.
HumphreyPP. 5-Hydroxytryptamine and the pathophysiology of migraine. J Neurology1991; 238(Suppl 1): S38–S44.
26.
LotheAMerletIDemarquayG. Interictal brain 5-HT1A receptors binding in migraine without aura: A 18F-MPPF-PET study. Cephalalgia2008; 28: 1282–1291.
27.
JuditASandorPSSchoenenJ. Habituation of visual and intensity dependence of auditory evoked cortical potentials tends to normalize just before and during the migraine attack. Cephalalgia2000; 20: 714–719.
28.
DemarquayGLotheARoyetJP. Brainstem changes in 5-HT1A receptor availability during migraine attack. Cephalalgia2011; 31: 84–94.
29.
Saengjaroentham C, Supornsilpchai W, Ji-Au W, et al. Serotonin depletion can enhance the cerebrovascular responses induced by cortical spreading depression via the nitric oxide pathway. Int J Neurosci. Epub ahead of print 2014 May 19.
ChangJCShookLLBiagJ. Biphasic direct current shift, haemoglobin desaturation and neurovascular uncoupling in cortical spreading depression. Brain2010; 133(Pt 4): 996–1012.
32.
PerkoDPretnar-OblakJSabovičM. Cerebrovascular reactivity to l-arginine in the anterior and posterior cerebral circulation in migraine patients. Acta Neurol Scand2011; 124: 269–274.
33.
MosekANovakVOpfer-GehrkingTL. Autonomic dysfunction in migraineurs. Headache1999; 39: 108–117.
34.
NakamuraTKawabeKSapruHN. Cold pressor test in the rat: Medullary and spinal pathways and neurotransmitters. Am J Physiol Heart Circ Physiol2008; 295: H1780–H1787.
35.
SamuelsERSzabadiE. Functional neuroanatomy of the noradrenergic locus coeruleus: Its roles in the regulation of arousal and autonomic function part I: Principles of functional organisation. Curr Neuropharmacol2008; 6: 235–253.
36.
SamuelsERSzabadiE. Functional neuroanatomy of the noradrenergic locus coeruleus: Its roles in the regulation of arousal and autonomic function part II: Physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans. Curr Neuropharmacol2008; 6: 254–285.
37.
TopcuogluMAAydinHSakaE. Occipital cortex activation studied with simultaneous recordings of functional transcranial Doppler ultrasound (fTCD) and visual evoked potential (VEP) in cognitively normal human subjects: Effect of healthy aging. Neurosci Lett2009; 452: 17–22.
