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Open Access 01-12-2018 | Research article

Increased thalamic glutamate/glutamine levels in migraineurs

Authors: Adina Bathel, Lauren Schweizer, Philipp Stude, Benjamin Glaubitz, Niklas Wulms, Sibel Delice, Tobias Schmidt-Wilcke

Published in: The Journal of Headache and Pain | Issue 1/2018

Abstract

Background

Increased cortical excitability has been hypothesized to play a critical role in various neurological disorders, such as restless legs syndrome, epilepsy and migraine. Particularly for migraine, local hyperexcitability has been reported. Levels of regional excitatory and inhibitory neurotransmitters are related to cortical excitability and hence may play a role in the origin of the disease. Consequently, a mismatch of the excitatory-inhibitory neurotransmitter network might contribute to local hyperexcitability and the onset of migraine attacks. In this study we sought to assess local levels of glutamate / glutamine (GLX) and gamma-aminobutyric acid (GABA) in the occipital cortex and right thalamus of migraineurs and healthy subjects.

Methods

We measured interictally local biochemical concentrations in the occipital lobe and the right thalamus in patients with migraine (without aura) and healthy controls (HCs) using proton magnetic resonance spectroscopy at 3 T. GLX levels were acquired using PRESS and GABA levels using the GABA-sensitive editing sequence MEGA-PRESS. Regional GLX and GABA levels were compared between groups.

Results

Statistical analyses revealed significantly increased GLX levels in both the primary occipital cortex and thalamus. However, we found no group differences in GABA levels for these two regions. Correlation analyses within the migraine group revealed no significant correlations between pain intensity and levels of GLX or GABA in either of the two brain regions.

Conclusions

Further research is needed to investigate the role of GABA/GLX ratios in greater depth and to measure changes in neurotransmitter levels over time, i.e. during migraine attacks and interictally.

Stovner LJ, Zwart JA, Hagen K, Terwindt GM, Pascual J (2006) Epidemiology of headache in Europe. Eur J Neurol. https://doi.org/10.1111/j.1468-1331.2006.01184.x

Weiller C, May A, Limmroth V et al (1995) Brain stem activation in spontaneous human migraine attacks. Nat Med. https://doi.org/10.1038/nm0795-658

Moskowitz MA (1990) Basic mechanisms in vascular headache. Neurol Clin 8(4):801–815.

Charles A (2009) Advances in the basic and clinical science of migraine. Ann Neurol. https://doi.org/10.1002/ana.21691

Quintas M, Neto JL, Pereira-Monteiro J et al (2013) Interaction between gamma-aminobutyric acid a receptor genes: new evidence in migraine susceptibility. PLoSOne. 2013;8(9):e74087. https://doi.org/10.1371/journal.pone.0074087

Chen T, Murrell M, Fowdar J, Roy B, Grealy R, Griffiths LR (2012) Investigation of the role of the GABRG2 gene variant in migraine. J Neurol Sci. https://doi.org/10.1016/j.jns.2012.03.014

Plummer PN, Colson NJ, Lewohl JM et al (2011) Significant differences in gene expression of GABA receptors in peripheral blood leukocytes of migraineurs. Gene doi:https://doi.org/10.1016/j.gene.2011.08.031; https://doi.org/10.1016/j.gene.2011.08.031

Fernandez F, Esposito T, Lea RA et al (2008) Investigation of gamma-aminobutyric acid (GABA) a receptors genes and migraine susceptibility. BMC Med Genet. https://doi.org/10.1186/1471-2350-9-109

Coppola G, Pierelli F, Schoenen J (2007) Is the cerebral cortex hyperexcitable or hyperresponsive in migraine? Cephalalgia. https://doi.org/10.1111/j.1468-2982.2007.01500.x

10.

Khedr EM, Ahmed MA, Mohamed KA (2006) Motor and visual cortical excitability in migraineurs patients with or without aura: transcranial magnetic stimulation. Neurophysiol Clin. https://doi.org/10.1016/j.neucli.2006.01.007

11.

Höffken O, Stude P, Lenz M, Bach M, Dinse HR, Tegenthoff M (2009) Visual paired-pulse stimulation reveals enhanced visual cortex excitability in migraineurs. Eur J Neurosci. https://doi.org/10.1111/j.1460-9568.2009.06859.x

12.

Zielman R, Wijnen JP, Webb A et al (2017) Cortical glutamate in migraine. Brain 140(7):1859–1871. https://doi.org/10.1093/brain/awx130 CrossRefPubMed

13.

Siniatchkin M, Sendacki M, Moeller F et al (2012) Abnormal changes of synaptic excitability in migraine with aura. Cereb Cortex 22(10):2207–2216. https://doi.org/10.1093/cercor/bhr248 CrossRefPubMed

14.

Aguila MER, Lagopoulos J, Leaver AM et al (2015) Elevated levels of GABA+ in migraine detected using1H-MRS. NMR Biomed. https://doi.org/10.1002/nbm.3321

15.

Bridge H, Stagg CJ, Near J, Lau CI, Zisner A, Zameel Cader M (2015) Altered neurochemical coupling in the occipital cortex in migraine with visual aura. Cephalalgia. https://doi.org/10.1177/0333102414566860

16.

Bigal ME, Hetherington H, Pan J et al (2008) Occipital levels of GABA are related to severe headaches in migraine. Neurology. https://doi.org/10.1212/01.wnl.0000313376.07248.28

17.

Magon S, May A, Stankewitz A et al (2015) Morphological abnormalities of thalamic subnuclei in migraine: a multicenter MRI study at 3 tesla. J Neurosci. https://doi.org/10.1523/JNEUROSCI.2154-15.2015

18.

Messina R, Rocca MA, Colombo B et al (2015) White matter microstructure abnormalities in pediatric migraine patients. Cephalalgia. https://doi.org/10.1177/0333102415578428

19.

Noseda R, Kainz V, Borsook D, Burstein R (2014) Neurochemical pathways that converge on thalamic trigeminovascular neurons: potential substrate for modulation of migraine by sleep, food intake, stress and anxiety. PLoS One. https://doi.org/10.1371/journal.pone.0103929

20.

Olesen J, Marie-Germaine B (2004) The international classification of headache disorders 2nd edition ICHD-ll. Headache. https://doi.org/10.1111/j.1526-4610.2008.01121.x

21.

Ferrari MD, Odink J, Bos KD, Malessy MJ, Bruyn GW (1990) Neuroexcitatory plasma amino acids are elevated in migraine. Neurology. 1990;40(10):1582–6.

22.

Dichgans M, Herzog J, Freilinger T, Wilke M, Auer DP (2005) 1H-MRS alterations in the cerebellum of patients with familial hemiplegic migraine type 1. Neurology. https://doi.org/10.1212/01.WNL.0000151855.98318.50

23.

Zielman R, Teeuwisse WM, Bakels F et al (2014) Biochemical changes in the brain of hemiplegic migraine patients measured with 7 tesla 1H-MRS. Cephalalgia. https://doi.org/10.1177/0333102414527016

24.

Petrou M, Pop-Busui R, Foerster BR et al (2012) Altered excitation-inhibition balance in the brain of patients with diabetic neuropathy. Acad Radiol. https://doi.org/10.1016/j.acra.2012.02.004

25.

Harris RE, Sundgren PC, Craig AD et al (2009) Elevated insular glutamate in fibromyalgia is associated with experimental pain. Arthritis Rheum 60(10):3146–3152. https://doi.org/10.1002/art.24849 CrossRefPubMedPubMedCentral

26.

Fayed N, Andres E, Rojas G et al (2012) Brain dysfunction in fibromyalgia and somatization disorder using proton magnetic resonance spectroscopy: a controlled study. Acta Psychiatr Scand. https://doi.org/10.1111/j.1600-0447.2011.01820.x

27.

Feraco P, Bacci a PF et al (2011) Metabolic abnormalities in pain-processing regions of patients with fibromyalgia: a 3T MR spectroscopy study. AJNR Am J Neuroradiol. https://doi.org/10.3174/ajnr.A2550

28.

Widerström-Noga E, Cruz-Almeida Y, Felix ER, Pattany PM (2015) Somatosensory phenotype is associated with thalamic metabolites and pain intensity after spinal cord injury. Pain. https://doi.org/10.1016/j.pain.0000000000000019

29.

Zunhammer M, Geis S, Busch V, Eichhammer P, Greenlee MW (2016) Pain modulation by intranasal oxytocin and emotional picture viewing-a randomized double-blind fMRI study. Sci Rep. https://doi.org/10.1038/srep31606

30.

Foerster BR, Petrou M, Edden RA et al (2012) Reduced insular gamma-aminobutyric acid in fibromyalgia. Arthritis Rheum 64(2):579–583. https://doi.org/10.1002/art.33339 CrossRefPubMedPubMedCentral

31.

Gustin SM, Wrigley PJ, Youssef AM et al (2014) Thalamic activity and biochemical changes in individuals with neuropathic pain after spinal cord injury. Pain 155(5):1027–1036. https://doi.org/10.1016/j.pain.2014.02.008. CrossRefPubMedPubMedCentral

32.

Henderson LA, Peck CC, Petersen ET et al (2013) Chronic pain: lost inhibition? J Neurosci 33(17):7574–7582. https://doi.org/10.1523/JNEUROSCI.0174-13.2013 CrossRefPubMed

Title: Increased thalamic glutamate/glutamine levels in migraineurs
Authors: Adina Bathel
Lauren Schweizer
Philipp Stude
Benjamin Glaubitz
Niklas Wulms
Sibel Delice
Tobias Schmidt-Wilcke
Publication date: 01-12-2018
Publisher: Springer Milan
Published in: The Journal of Headache and Pain / Issue 1/2018
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-018-0885-8

At a glance: The STEP trials

Springer Medicine

Increased thalamic glutamate/glutamine levels in migraineurs

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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