Energy Metabolism Impairment in Migraine

Page: [6253 - 6260] Pages: 8

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Abstract

Migraine is a common disabling neurological disorder which is characterised by a recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an updated overview of the energy metabolism involvement in the migraine pathophysiology. Several biochemical, morphological and magnetic resonance spectroscopy studies have confirmed the presence of energy production deficiency together with an increment of energy consumption in migraine patients. An increment of energy demand over a certain threshold creates metabolic and biochemical preconditions for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis that improving brain energy metabolism may reduce the susceptibility to migraine.

Keywords: Energy metabolism, mitochondrial dysfunction, migraine, oxidative phosphorylation, magnetic resonance spectroscopy, bioenergetics defect.

[1]
Montagna, P.; Sacquegna, T.; Martinelli, P.; Cortelli, P.; Bresolin, N.; Moggio, M.; Baldrati, A.; Riva, R.; Lugaresi, E. Mitochondrial abnormalities in migraine. Preliminary findings. Headache, 1988, 28(7), 477-480.
[http://dx.doi.org/10.1111/j.1526-4610.1988.hed2807477.x] [PMID: 3243709]
[2]
Vollono, C.; Primiano, G.; Della Marca, G.; Losurdo, A.; Servidei, S. Migraine in mitochondrial disorders: Prevalence and characteristics. Cephalalgia, 2017, 1, 1-14.
[http://dx.doi.org/ 10.1177/0333102417723568] [PMID: 28762753]
[3]
Tonon, C.; Pierangeli, G.; Cevoli, S.; Cortelli, P.; Lodi, R. Metabolites and migraine. In: Borsook, D.; May, A.; Goadsby, P.J.; Hargreaves R. The migraine Brain; Oxford University Press, 2012; pp. 251-273.
[http://dx.doi.org/10.1093/acprof:oso/9780199754564.003.0023]
[4]
Okada, H.; Araga, S.; Takeshima, T.; Nakashima, K. Plasma lactic acid and pyruvic acid levels in migraine and tension-type headache. Headache, 1998, 38(1), 39-42.
[http://dx.doi.org/10.1046/j.1526-4610.1998.3801039.x] [PMID: 9505002]
[5]
Cevoli, S.; Pallotti, F.; La Morgia, C.; Valentino, M.L.; Pierangeli, G.; Cortelli, P.; Baruzzi, A.; Montagna, P.; Carelli, V. High frequency of migraine-only patients negative for the 3243 A>G tRNALeu mtDNA mutation in two MELAS families. Cephalalgia, 2010, 30(8), 919-927.
[http://dx.doi.org/10.1177/0333102409354654] [PMID: 20656703]
[6]
Sangiorgi, S.; Mochi, M.; Riva, R.; Cortelli, P.; Monari, L.; Pierangeli, G.; Montagna, P. Abnormal platelet mitochondrial function in patients affected by migraine with and without aura. Cephalalgia, 1994, 14(1), 21-23.
[http://dx.doi.org/10.1046/j.1468-2982.1994.1401021.x] [PMID: 8200018]
[7]
D’Andrea, G.; D’Arrigo, A.; Dalle Carbonare, M.; Leon, A. Pathogenesis of migraine: role of neuromodulators. Headache, 2012, 52(7), 1155-1163.
[http://dx.doi.org/10.1111/j.1526-4610.2012.02168.x] [PMID: 22671857]
[8]
Sparaco, M.; Feleppa, M.; Lipton, R.B.; Rapoport, A.M.; Bigal, M.E. Mitochondrial dysfunction and migraine: evidence and hypotheses. Cephalalgia, 2006, 26(4), 361-372.
[http://dx.doi.org/10.1111/j.1468-2982.2005.01059.x] [PMID: 16556237]
[9]
Younis, S.; Hougaard, A.; Vestergaard, M.B.; Larsson, H.B.W.; Ashina, M. Migraine and magnetic resonance spectroscopy: a systematic review. Curr. Opin. Neurol., 2017, 30(3), 246-262.
[http://dx.doi.org/10.1097/WCO.0000000000000436] [PMID: 28240609]
[10]
Chance, B.; Nioka, S.; Leigh, J.S. Metabolic control principles: importance of the steady-state reaffirmed and quantified by 31-PMRS. Oxygen transport utilization; Bryan-Brown, C.W; Hires, S.M., Ed.; Society of Critical Care Medicine, 1987, pp. 215-228.
[11]
Taylor, D.J.; Fleckenstein, J.L.; Lodi, R. Magnetic resonance imaging and spectroscopy of muscle. Disorders of Voluntary Muscle (7th Edition);, Karpati, G.; Hilton-Jones, D.; Griggs, R.C., Eds.; Cambridge University Press: Cambridge,. 2001, 319-346.
[12]
Welch, K.M.; Levine, S.R.; D’Andrea, G.; Helpern, J.A. Brain pH in migraine: an in vivo phosphorus-31 magnetic resonance spectroscopy study. Cephalalgia, 1988, 8(4), 273-277.
[http://dx.doi.org/10.1046/j.1468-2982.1988.0804273.x] [PMID: 3219729]
[13]
Welch, K.M.; Levine, S.R.; D’Andrea, G.; Schultz, L.R.; Helpern, J.A. Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 31 NMR spectroscopy. Neurology, 1989, 39(4), 538-541.
[http://dx.doi.org/10.1212/WNL.39.4.538] [PMID: 2927679]
[14]
Barbiroli, B.; Montagna, P.; Cortelli, P.; Martinelli, P.; Sacquegna, T.; Zaniol, P.; Lugaresi, E. Complicated migraine studied by phosphorus magnetic resonance spectroscopy. Cephalalgia, 1990, 10(5), 263-272.
[http://dx.doi.org/10.1046/j.1468-2982.1990.1005263.x] [PMID: 2272097]
[15]
Barbiroli, B.; Montagna, P.; Cortelli, P.; Funicello, R.; Iotti, S.; Monari, L.; Pierangeli, G.; Zaniol, P.; Lugaresi, E. Abnormal brain and muscle energy metabolism shown by 31P magnetic resonance spectroscopy in patients affected by migraine with aura. Neurology, 1992, 42(6), 1209-1214.
[http://dx.doi.org/10.1212/WNL.42.6.1209] [PMID: 1603349]
[16]
Montagna, P.; Cortelli, P.; Monari, L.; Pierangeli, G.; Parchi, P.; Lodi, R.; Iotti, S.; Frassineti, C.; Zaniol, P.; Lugaresi, E. 31P-magnetic resonance spectroscopy in migraine without aura. Neurology, 1994, 44(4), 666-669.
[http://dx.doi.org/10.1212/WNL.44.4.666] [PMID: 8164822]
[17]
Schulz, U.G.; Blamire, A.M.; Davies, P.; Styles, P.; Rothwell, P.M. Normal cortical energy metabolism in migrainous stroke: A 31P-MR spectroscopy study. Stroke, 2009, 40(12), 3740-3744.
[http://dx.doi.org/10.1161/STROKEAHA.109.558163] [PMID: 19834021]
[18]
Yorns, W.R., Jr; Hardison, H.H. Mitochondrial dysfunction in migraine. Semin. Pediatr. Neurol., 2013, 20(3), 188-193.
[http://dx.doi.org/10.1016/j.spen.2013.09.002] [PMID: 24331360]
[19]
Sarchielli, P.; Tarducci, R.; Presciutti, O.; Gobbi, G.; Pelliccioli, G.P.; Stipa, G.; Alberti, A.; Capocchi, G. Functional 1H-MRS findings in migraine patients with and without aura assessed interictally. Neuroimage, 2005, 24(4), 1025-1031.
[http://dx.doi.org/10.1016/j.neuroimage.2004.11.005] [PMID: 15670679]
[20]
Reyngoudt, H.; Paemeleire, K.; Dierickx, A.; Descamps, B.; Vandemaele, P.; De Deene, Y.; Achten, E. Does visual cortex lactate increase following photic stimulation in migraine without aura patients? A functional (1)H-MRS study. J. Headache Pain, 2011, 12(3), 295-302.
[http://dx.doi.org/10.1007/s10194-011-0295-7] [PMID: 21301922]
[21]
Welch, K.M.A.; Ramadan, N.M. Mitochondria, magnesium and migraine. J. Neurol. Sci., 1995, 134(1-2), 9-14.
[http://dx.doi.org/10.1016/0022-510X(95)00196-1] [PMID: 8747836]
[22]
Ramadan, N.M.; Halvorson, H.; Vande-Linde, A.; Levine, S.R.; Helpern, J.A.; Welch, K.M. Low brain magnesium in migraine. Headache, 1989, 29(9), 590-593.
[http://dx.doi.org/10.1111/j.1526-4610.1989.hed2909590.x] [PMID: 2584000]
[23]
Barbiroli, B.; Iotti, S.; Cortelli, P.; Martinelli, P.; Lodi, R.; Carelli, V.; Montagna, P. Low brain intracellular free magnesium in mitochondrial cytopathies. J. Cereb. Blood Flow Metab., 1999, 19(5), 528-532.
[http://dx.doi.org/10.1097/00004647-199905000-00007] [PMID: 10326720]
[24]
Lodi, R.; Iotti, S.; Cortelli, P.; Pierangeli, G.; Cevoli, S.; Clementi, V.; Soriani, S.; Montagna, P.; Barbiroli, B. Deficient energy metabolism is associated with low free magnesium in the brains of patients with migraine and cluster headache. Brain Res. Bull., 2001, 54(4), 437-441.
[http://dx.doi.org/10.1016/S0361-9230(01)00440-3] [PMID: 11306197]
[25]
Stuart, S.; Griffiths, L.R. A possible role for mitochondrial dysfunction in migraine. Mol. Genet. Genomics, 2012, 287(11-12), 837-844.
[http://dx.doi.org/10.1007/s00438-012-0723-7] [PMID: 23052833]
[26]
Majamaa, K.; Finnilä, S.; Turkka, J.; Hassinen, I.E. Mitochondrial DNA haplogroup U as a risk factor for occipital stroke in migraine. Lancet, 1998, 352(9126), 455-456.
[http://dx.doi.org/10.1016/S0140-6736(05)79190-X] [PMID: 9708761]
[27]
Fachal, L.; Mosquera-Miguel, A.; Pastor, P.; Ortega-Cubero, S.; Lorenzo, E.; Oterino-Durán, A.; Toriello, M.; Quintáns, B.; Camiña-Tato, M.; Sesar, A.; Vega, A.; Sobrido, M.J.; Salas, A. No evidence of association between common European mitochondrial DNA variants in Alzheimer, Parkinson, and migraine in the Spanish population. Am J Genet,, 2014, 168(B), 54-65.
[http://dx.doi.org/10.1002/ajmg.b.32276] [PMID: 25349034]
[28]
Roos-Araujo, D.; Stuart, S.; Lea, R.A.; Haupt, L.M.; Griffiths, L.R. Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility. Gene, 2014, 543(1), 1-7.
[http://dx.doi.org/10.1016/j.gene.2014.04.001] [PMID: 24704026]
[29]
Markley, H.G. CoEnzyme Q10 and riboflavin: the mitochondrial connection. Headache, 2012, 52(Suppl. 2), 81-87.
[http://dx.doi.org/10.1111/j.1526-4610.2012.02233.x] [PMID: 23030537]
[30]
Schoenen, J.; Jacquy, J.; Lenaerts, M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology, 1998, 50(2), 466-470.
[http://dx.doi.org/10.1212/WNL.50.2.466] [PMID: 9484373]
[31]
Sándor, P.S.; Di Clemente, L.; Coppola, G.; Saenger, U.; Fumal, A.; Magis, D.; Seidel, L.; Agosti, R.M.; Schoenen, J. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology, 2005, 64(4), 713-715.
[http://dx.doi.org/10.1212/01.WNL.0000151975.03598.ED] [PMID: 15728298]
[32]
Gaul, C.; Diener, H.C.; Danesch, U. Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial. J. Headache Pain, 2015, 16, 516.
[http://dx.doi.org/10.1186/s10194-015-0516-6] [PMID: 25916335]
[33]
von Luckner, A.; Riederer, F. Magnesium in migraine prophylaxis-is there an evidence-based rationale? a systematic review. Headache, 2018, 58(2), 199-209.
[http://dx.doi.org/10.1111/head.13217] [PMID: 29131326]
[34]
Di Lorenzo, C.; Coppola, G.; Sirianni, G.; Di Lorenzo, G.; Bracaglia, M.; Di Lenola, D.; Siracusano, A.; Rossi, P.; Pierelli, F. Migraine improvement during short lasting ketogenesis: a proof-of-concept study. Eur. J. Neurol., 2015, 22(1), 170-177.
[http://dx.doi.org/10.1111/ene.12550] [PMID: 25156013]
[35]
Barbanti, P.; Fofi, L.; Aurilia, C.; Egeo, G.; Caprio, M. Ketogenic diet in migraine: rationale, findings and perspectives. Neurol. Sci., 2017, 38(Suppl. 1), 111-115.
[http://dx.doi.org/10.1007/s10072-017-2889-6] [PMID: 28527061]
[36]
Di Lorenzo, C.; Coppola, G.; Bracaglia, M.; Di Lenola, D.; Evangelista, M.; Sirianni, G.; Rossi, P.; Di Lorenzo, G.; Serrao, M.; Parisi, V.; Pierelli, F. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study. J. Headache Pain, 2016, 17, 58.
[http://dx.doi.org/10.1186/s10194-016-0650-9] [PMID: 27245682]