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The Link Between Glutamate and Migraine

Published online by Cambridge University Press:  07 November 2014

Nabih M. Ramadan
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Abstract

Migraine pain-relay centers, including the trigeminal ganglion, trigeminal nucleus caudalis, and thalamus, contain glutamate-positive neurons, and glutamate activates the trigeminal nucleus caudalis. Glutamate is implicated in cortical spreading depression, trigeminovascular activation, and central sensitization. Glutamate receptor-subtype antagonists are effective in preclinical models of migraine, and in the clinic. These preclinical and clinical observations argue for a strong link between migraine and the glutamatergic system, a link that is important to further characterize in an effort to better understand migraine mechanisms and deliver effective therapies.

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Type
Review
Information
CNS Spectrums , Volume 8 , Issue 6: Migraines: Neurological and Psychiatric Perspectives , June 2003 , pp. 446 - 449
Copyright
Copyright © Cambridge University Press 2003

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References

REFERENCES

1.Bleakman, D, Lodge, D. Neuropharmacology of AMPA and kainate receptors. Neuropharmacology. 1998;37:1187–1204.CrossRefGoogle ScholarPubMed
2.Fundytus, ME. Glutamate receptors and nociception: implications for the drug treatment of pain. CNS Drugs. 2001;15:29–58.CrossRefGoogle ScholarPubMed
3.Schoepp, DD, Conn, PJ. Metabotropic glutamate receptors in brain function and pathology. Trends Pharmacol Sci. 1993;14:13–20.CrossRefGoogle ScholarPubMed
4.Hill, RG, Salt, TE. An ionophoretic study of the responses of rat caudal trigeminal nucleus neurons to non-noxious mechanical sensory stimuli. J Physiol. 1982;327:65–78.CrossRefGoogle ScholarPubMed
5.Bereiter, D.A. and Benetti, A.P.Excitatory amino acid release within spinal trigeminal nucleus after mustard oil injection into the temporomandibular joint region of the rat. Pain. 1996;67:451–459.CrossRefGoogle ScholarPubMed
6.Sahara, Y, Noro, N, Iida, Y, Soma, K, Nakamura, Y. Glutamate receptor subunits GluR5 and KA-2 are coexpressed in rat trigeminal ganglion neurons. J Neurosci. 1997;17:6611–6620.CrossRefGoogle ScholarPubMed
7.Quartu, M, Serra, MP, Ambu, R, Lai, ML, Del Fiacco, M. AMPA-type glutamate receptor subunits 2/3 in the human trigeminal sensory ganglion and subnucleus caudalis from prenatal ages to adulthood. Mech Ageing Dev. 2002;123:463–471.CrossRefGoogle ScholarPubMed
8.Tallaksen-Greene, SJ, Young, AB, Penney, JB, Beitz, AJ. Excitatory amino acid binding sites in the trigeminal principal sensory and spinal trigeminal nuclei of the rat. Neurosci Lett. 141:79–83.CrossRefGoogle Scholar
9.Ma, QP. Co-localization of 5-HT (1B/1D/1F) receptors and glutamate in trigeminal ganglia in rats. Neuroreport. 2001;12:1589–1591.CrossRefGoogle Scholar
10.Scheller, D, Szathmary, S, Kolb, J, Tegtmeier, F. Observations on the relationship between the extracellular changes of taurine and glutamate during cortical spreading depression, during ischemia, and within the area surrounding a thrombotic infarct. Amino Acids. 2000;19:571–583.CrossRefGoogle ScholarPubMed
11.Lauritzen, M, Hansen, AJ. The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression. J Cereb Blood Flow Metab. 1992;12:223–229.CrossRefGoogle ScholarPubMed
12.Obrenovitch, TP, Zilkha, E, Urenjak, J. Evidence against high extracellular glutamate promoting the elicitation of spreading depression by potassium. J Cereb Blood Flow Metab. 1996;16:923–931.CrossRefGoogle ScholarPubMed
13.Mody, I, Lambert, JD, Heinemann, U. Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices. J Neurophysiol. 1987;57:869–888.CrossRefGoogle ScholarPubMed
14.Nellgard, B, Wieloch, T. NMDA-receptor blockers but not NBQX, an AMPA-receptor antagonist, inhibit spreading depression in the rat brain. Acta Physiol Scand. 1992;146:497–503.CrossRefGoogle Scholar
15.Johnson, KW, Dieckman, DK, Phebus, LA, et al.iGluR5 antagonists as novel migraine therapies [abstract]. Cephalalgia. 2001;21:268.Google Scholar
16.Mitsikostas, DD, Sanchez del Rio, M, Waeber, C, Huang, Z, Cutrer, FM, Moskowitz, MA. Non-NMDA glutamate receptors modulate capsaicin induced c-fos expression within trigeminal nucleus caudalis. Br J Pharmacol. 1999;127:623–630.CrossRefGoogle ScholarPubMed
17.Goadsby, PJ, Classey, JD. Glutamatergic transmission in the trigeminal nucleus assessed with local blood flow. Brain Res. 2000;875:119–124.CrossRefGoogle ScholarPubMed
18.Storer, RJ, Goadsby, PJ. Trigeminovascular nociceptive transmission involves N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate receptors. Neuroscience. 1999;90:1371–1376.CrossRefGoogle ScholarPubMed
19.Ferrari, MD, Odink, J, Bos, KD, Malessy, MJ, Bruyn, GW. Neuroexcitatory plasma amino acids are elevated in migraine. Neurology. 1990;40:1582–1586.CrossRefGoogle ScholarPubMed
20.D'Andrea, G, Cananzi, AR, Joseph, R, et al.Platelet glycine, glutamate and aspartate in primary headache. Cephalalgia. 1991;11:197–200.CrossRefGoogle ScholarPubMed
21.Martinez, F, Castillo, J, Rodriguez, JR, Leira, R, Noya, M. Neuroexcitatory amino acid levels in plasma and cerebrospinal fluid during migraine attacks. Cephalalgia. 1993;13:89–93.CrossRefGoogle ScholarPubMed
22.Cananzi, AR, D'Andrea, G, Perini, F, Zamberlan, F, Welch, KM. Platelet and plasma levels of glutamate and glutamine in migraine with and without aura. Cephalalgia. 1995;15:132–135.CrossRefGoogle ScholarPubMed
23.D'Eufemia, P, Finocchiaro, R, Lendvai, D, et al.Erythrocyte and plasma levels of glutamate and aspartate in children affected by migraine. Cephalalgia. 1997;17:652–657CrossRefGoogle ScholarPubMed
24.Alam, Z, Coombes, N, Waring, RH, Williams, AC, Steventon, GB. Plasma levels of neuroexcitatory amino acids in patients with migraine or tension headache. J Neurol Sci. 1998;156:102–106.CrossRefGoogle ScholarPubMed
25.Burnstein, R, Yarnitsky, D, Goor-Aryeh, I, Ransil, BJ, Bajwa, ZH. An association between migraine and cutaneous allodynia. Ann Neurol. 2000;47:614–624.3.0.CO;2-N>CrossRefGoogle Scholar
26.Burstein, R. Deconstructing migraine headache into peripheral and central sensitization. Pain. 2001;89:107–110.CrossRefGoogle ScholarPubMed
27.Katsarava, Z, Lehnerdt, G, Duda, B, Ellrich, J, Diener, HC, Kaube, H. Sensitization of trigeminal nociception specific for migraine but not pain of sinusitis. Neurology. 2002;59:1450–1453.CrossRefGoogle Scholar
28.Kaube, H, Herzog, J, Kaufer, T, Dichgans, M, Diener, HC. Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine. Neurology. 2000;55:139–141.CrossRefGoogle ScholarPubMed
29.Ramadan, N, Sang, C, Chappell, A, et al.IV LY293558, an AMPA/KA receptor antagonist, is effective in migraine [abstract]. Cephalalgia. 2001;21:267–268.Google Scholar