Circulating Biomarkers in Migraine: New Opportunities for Precision Medicine

Author(s): Patrizia Ferroni*, Piero Barbanti, Antonella Spila, Federica Fratangeli, Cinzia Aurilia, Luisa Fofi, Gabriella Egeo, Fiorella Guadagni

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 34 , 2019

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Background: Migraine is the most common neurological disorder and the second most disabling human condition, whose pathogenesis is favored by a combination of genetic, epigenetic, and environmental factors. In recent years, several efforts have been made to identify reliable biomarker(s) useful to monitor disease activity and/or ascertain the response to a specific treatment.

Objective: To review the current evidence on the potential biological markers associated with migraine.

Methods: A structured search of peer-reviewed research literature was performed by searching major publications databases up to December 2017.

Results: Several circulating biomarkers have been proposed as diagnostic or therapeutic tools in migraine, mostly related to migraine’s inflammatory pathophysiological aspects. Nonetheless, their detection is still a challenge for the scientific community, reflecting, at least in part, disease complexity and clinical diagnostic limitations. At the present time, calcitonin generelated peptide (CGRP) represents probably the most promising candidate as a diagnostic and/or therapeutic biomarker, as its plasma levels are elevated during migraine attack and decrease during successful treatment. Other molecules (including some neuropeptides, cytokines, adipokines, or vascular activation markers) despite promising, do not possess the sufficient prerequisites to be considered as migraine biomarkers.

Conclusion: The characterization of migraine-specific biomarkers would be fundamental in a perspective of precision medicine, enabling risk assessment and tailored treatments. However, speculating on the clinical validity of migraine biomarkers may be premature and controlled clinical trials are presently needed to investigate both the diagnostic and therapeutic value of these biomarkers in migraine.

Keywords: Migraine, headache, inflammation, biomarkers, calcitonin gene-related peptide, cytokines, highsensitive C reactive protein.

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet, 2017, 390(10100), 1211-1259.
[] [PMID: 28919117]
Stewart, W.F.; Roy, J.; Lipton, R.B. Migraine prevalence, socioeconomic status, and social causation. Neurology, 2013, 81(11), 948-955.
[] [PMID: 23990405]
Vetvik, K.G.; MacGregor, E.A. Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Lancet Neurol., 2017, 16(1), 76-87.
[] [PMID: 27836433]
Le, H.; Tfelt-Hansen, P.; Skytthe, A.; Kyvik, K.O.; Olesen, J. Association between migraine, lifestyle and socioeconomic factors: a population-based cross-sectional study. J. Headache Pain, 2011, 12(2), 157-172.
[] [PMID: 21390550]
Varkey, E.; Hagen, K.; Zwart, J.A.; Linde, M. Physical activity and headache: results from the Nord-trøndelag health study (HUNT). Cephalalgia, 2008, 28(12), 1292-1297.
[] [PMID: 18771495]
Varkey, E.; Cider, A.; Carlsson, J.; Linde, M. Exercise as migraine prophylaxis: a randomized study using relaxation and topiramate as controls. Cephalalgia, 2011, 31(14), 1428-1438.
[] [PMID: 21890526]
Bigal, M.E.; Liberman, J.N.; Lipton, R.B. Obesity and migraine: a population study. Neurology, 2006, 66(4), 545-550.
[] [PMID: 16354886]
Bigal, M.E.; Tsang, A.; Loder, E.; Serrano, D.; Reed, M.L.; Lipton, R.B. Body mass index and episodic headaches: a population-based study. Arch. Intern. Med., 2007, 167(18), 1964-1970.
[] [PMID: 17923596]
Taylor, F.R. Tobacco, nicotine, and headache. Headache, 2015, 55(7), 1028-1044.
[] [PMID: 26140522]
Dueland, A.N. Headache and alcohol. Headache, 2015, 55(7), 1045-1049.
[] [PMID: 26121267]
Aurora, S.K.; Brin, M.F. Chronic migraine: an update on physiology, imaging, and the mechanism of action of two available pharmacologic therapies. Headache, 2017, 57(1), 109-125.
[] [PMID: 27910097]
Goadsby, P.J.; Holland, P.R.; Martins-Oliveira, M.; Hoffmann, J.; Schankin, C.; Akerman, S. Pathophysiology of migraine: a disorder of sensory processing. Physiol. Rev., 2017, 97(2), 553-622.
[] [PMID: 28179394]
Pietrobon, D.; Moskowitz, M.A. Pathophysiology of migraine. Annu. Rev. Physiol., 2013, 75, 365-391.
[] [PMID: 23190076]
Tozzi, A.; de Iure, A.; Di Filippo, M.; Costa, C.; Caproni, S.; Pisani, A.; Bonsi, P.; Picconi, B.; Cupini, L.M.; Materazzi, S.; Geppetti, P.; Sarchielli, P.; Calabresi, P. Critical role of calcitonin gene-related peptide receptors in cortical spreading depression. Proc. Natl. Acad. Sci. USA, 2012, 109(46), 18985-18990.
[] [PMID: 23112192]
Russell, F.A.; King, R.; Smillie, S.J.; Kodji, X.; Brain, S.D. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol. Rev., 2014, 94(4), 1099-1142.
[] [PMID: 25287861]
Barbanti, P.; Aurilia, C.; Fofi, L.; Egeo, G.; Ferroni, P. The role of anti-CGRP antibodies in the pathophysiology of primary headaches. Neurol. Sci., 2017, 38(Suppl. 1), 31-35.
[] [PMID: 28527063]
Hay, D.L.; Walker, C.S. CGRP and its receptors. Headache, 2017, 57(4), 625-636.
[] [PMID: 28233915]
Storer, R.J.; Akerman, S.; Goadsby, P.J. Calcitonin Gene-related Peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat. Br. J. Pharmacol., 2004, 142(7), 1171-1181.
[] [PMID: 15237097]
Brain, S.D.; Grant, A.D. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol. Rev., 2004, 84(3), 903-934.
[] [PMID: 15269340]
Edvinsson, L. The trigeminovascular pathway: role of CGRP and CGRP receptors in migraine. Headache, 2017, 57(Suppl. 2), 47-55.
[] [PMID: 28485848]
Goadsby, P.J.; Edvinsson, L.; Ekman, R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann. Neurol., 1990, 28(2), 183-187.
[] [PMID: 1699472]
Guo, S.; Christensen, A.F.; Liu, M.L.; Janjooa, B.N.; Olesen, J.; Ashina, M. Calcitonin gene-related peptide induced migraine attacks in patients with and without familial aggregation of migraine. Cephalalgia, 2017, 37(2), 114-124.
[] [PMID: 26994300]
Guo, S.; Vollesen, A.L.; Olesen, J.; Ashina, M. Premonitory and nonheadache symptoms induced by CGRP and PACAP38 in patients with migraine. Pain, 2016, 157(12), 2773-2781.
[] [PMID: 27842045]
Hansen, J.M.; Hauge, A.W.; Olesen, J.; Ashina, M. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia, 2010, 30(10), 1179-1186.
[] [PMID: 20855363]
Ho, T.W.; Edvinsson, L.; Goadsby, P.J. CGRP and its receptors provide new insights into migraine pathophysiology. Nat. Rev. Neurol., 2010, 6(10), 573-582.
[] [PMID: 20820195]
Bell, I.M. Calcitonin gene-related peptide receptor antagonists: new therapeutic agents for migraine. J. Med. Chem., 2014, 57(19), 7838-7858.
[] [PMID: 24960305]
Boettger, M.K.; Weber, K.; Grossmann, D.; Gajda, M.; Bauer, R.; Bär, K.J.; Schulz, S.; Voss, A.; Geis, C.; Bräuer, R.; Schaible, H.G. Spinal tumor necrosis factor alpha neutralization reduces peripheral inflammation and hyperalgesia and suppresses autonomic responses in experimental arthritis: a role for spinal tumor necrosis factor alpha during induction and maintenance of peripheral inflammation. Arthritis Rheum., 2010, 62(5), 1308-1318.
[] [PMID: 20213802]
Schäfers, M.; Sommer, C.; Geis, C.; Hagenacker, T.; Vandenabeele, P.; Sorkin, L.S. Selective stimulation of either tumor necrosis factor receptor differentially induces pain behavior in vivo and ectopic activity in sensory neurons in vitro. Neuroscience, 2008, 157(2), 414-423.
[] [PMID: 18838115]
Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther., 2001, 69(3), 89-95.
[] [PMID: 11240971]
Sarchielli, P.; Pini, L.A.; Zanchin, G.; Alberti, A.; Maggioni, F.; Rossi, C.; Floridi, A.; Calabresi, P. Clinical-biochemical correlates of migraine attacks in rizatriptan responders and non-responders. Cephalalgia, 2006, 26(3), 257-265.
[] [PMID: 16472331]
Gallai, V.; Sarchielli, P.; Floridi, A.; Franceschini, M.; Codini, M.; Glioti, G.; Trequattrini, A.; Palumbo, R. Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally. Cephalalgia, 1995, 15(5), 384-390.
[] [PMID: 8536297]
Ashina, M.; Bendtsen, L.; Jensen, R.; Schifter, S.; Olesen, J. Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks. Pain, 2000, 86(1-2), 133-138.
[] [PMID: 10779670]
Fusayasu, E.; Kowa, H.; Takeshima, T.; Nakaso, K.; Nakashima, K. Increased plasma substance P and CGRP levels, and high ACE activity in migraineurs during headache-free periods. Pain, 2007, 128(3), 209-214.
[] [PMID: 17123735]
Cernuda-Morollón, E.; Larrosa, D.; Ramón, C.; Vega, J.; Martínez-Camblor, P.; Pascual, J. Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology, 2013, 81(14), 1191-1196.
[] [PMID: 23975872]
Jang, M.U.; Park, J.W.; Kho, H.S.; Chung, S.C.; Chung, J.W. Plasma and saliva levels of nerve growth factor and neuropeptides in chronic migraine patients. Oral Dis., 2011, 17(2), 187-193.
[] [PMID: 20659258]
Bellamy, J.L.; Cady, R.K.; Durham, P.L. Salivary levels of CGRP and VIP in rhinosinusitis and migraine patients. Headache, 2006, 46(1), 24-33.
[] [PMID: 16412148]
Cady, R.K.; Vause, C.V.; Ho, T.W.; Bigal, M.E.; Durham, P.L. Elevated saliva calcitonin gene-related peptide levels during acute migraine predict therapeutic response to rizatriptan. Headache, 2009, 49(9), 1258-1266.
[] [PMID: 19788468]
Sarchielli, P.; Alberti, A.; Floridi, A.; Gallai, V. Levels of nerve growth factor in cerebrospinal fluid of chronic daily headache patients. Neurology, 2001, 57(1), 132-134.
[] [PMID: 11445643]
van Dongen, R.M.; Zielman, R.; Noga, M.; Dekkers, O.M.; Hankemeier, T.; van den Maagdenberg, A.M.; Terwindt, G.M.; Ferrari, M.D. Migraine biomarkers in cerebrospinal fluid: A systematic review and meta-analysis. Cephalalgia, 2017, 37(1), 49-63.
[] [PMID: 26888294]
Goadsby, P.J.; Edvinsson, L. Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies. Brain, 1994, 117(Pt 3), 427-434.
[] [PMID: 7518321]
Neeb, L.; Anders, L.; Euskirchen, P.; Hoffmann, J.; Israel, H.; Reuter, U. Corticosteroids alter CGRP and melatonin release in cluster headache episodes. Cephalalgia, 2015, 35(4), 317-326.
[] [PMID: 24958681]
Tfelt-Hansen, P.; Le, H. Calcitonin gene-related peptide in blood: is it increased in the external jugular vein during migraine and cluster headache? A review. J. Headache Pain, 2009, 10(3), 137-143.
[] [PMID: 19330286]
Tvedskov, J.F.; Lipka, K.; Ashina, M.; Iversen, H.K.; Schifter, S.; Olesen, J. No increase of calcitonin gene-related peptide in jugular blood during migraine. Ann. Neurol., 2005, 58(4), 561-568.
[] [PMID: 16178016]
Edvinsson, L.; Ekman, R.; Goadsby, P.J. Measurement of vasoactive neuropeptides in biological materials: problems and pitfalls from 30 years of experience and novel future approaches. Cephalalgia, 2010, 30(6), 761-766.
[] [PMID: 20925142]
Goadsby, P.J.; Edvinsson, L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann. Neurol., 1993, 33(1), 48-56.
[] [PMID: 8388188]
Cernuda-Morollón, E.; Martínez-Camblor, P.; Ramón, C.; Larrosa, D.; Serrano-Pertierra, E.; Pascual, J. CGRP and VIP levels as predictors of efficacy of Onabotulinumtoxin type A in chronic migraine. Headache, 2014, 54(6), 987-995.
[] [PMID: 24673487]
Domínguez, C.; Vieites-Prado, A.; Pérez-Mato, M.; Sobrino, T.; Rodríguez-Osorio, X.; López, A.; Campos, F.; Martínez, F.; Castillo, J.; Leira, R. CGRP and PTX3 as predictors of efficacy of onabotulinumtoxin Type A in chronic migraine: an observational study. Headache, 2018, 58(1), 78-87.
[] [PMID: 29131327]
Cernuda-Morollón, E.; Ramón, C.; Martínez-Camblor, P.; Serrano-Pertierra, E.; Larrosa, D.; Pascual, J. OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine. Pain, 2015, 156(5), 820-824.
[] [PMID: 25735000]
Cady, R.; Turner, I.; Dexter, K.; Beach, M.E.; Cady, R.; Durham, P. An exploratory study of salivary calcitonin gene-related peptide levels relative to acute interventions and preventative treatment with onabotulinumtoxinA in chronic migraine. Headache, 2014, 54(2), 269-277.
[] [PMID: 24147647]
Tajti, J.; Szok, D.; Majláth, Z.; Tuka, B.; Csáti, A.; Vécsei, L. Migraine and neuropeptides. Neuropeptides, 2015, 52, 19-30.
[] [PMID: 26094101]
Riesco, N.; Cernuda-Morollón, E.; Pascual, J. Neuropeptides as a marker for chronic headache. Curr. Pain Headache Rep., 2017, 21(4), 18.
[] [PMID: 28281109]
Edvinsson, L.; Goadsby, P.J. Neuropeptides in migraine and cluster headache. Cephalalgia, 1994, 14(5), 320-327.
[] [PMID: 7828188]
Cernuda-Morollón, E.; Martínez-Camblor, P.; Alvarez, R.; Larrosa, D.; Ramón, C.; Pascual, J. Increased VIP levels in peripheral blood outside migraine attacks as a potential biomarker of cranial parasympathetic activation in chronic migraine. Cephalalgia, 2015, 35(4), 310-316.
[] [PMID: 24847167]
Riesco, N.; Cernuda-Morollón, E.; Martínez-Camblor, P.; Pérez-Alvarez, A.I.; Verano, L.; García-Cabo, C.; Serrano-Pertierra, E.; Pascual, J. Relationship between serum levels of VIP, but not of CGRP, and cranial autonomic parasympathetic symptoms: A study in chronic migraine patients. Cephalalgia, 2017, 37(9), 823-827.
[] [PMID: 27250233]
Zagami, A.S.; Edvinsson, L.; Goadsby, P.J. Pituitary adenylate cyclase activating polypeptide and migraine. Ann. Clin. Transl. Neurol., 2014, 1(12), 1036-1040.
[] [PMID: 25574477]
Tuka, B.; Helyes, Z.; Markovics, A.; Bagoly, T.; Szolcsányi, J.; Szabó, N.; Tóth, E.; Kincses, Z.T.; Vécsei, L.; Tajti, J. Alterations in PACAP-38-like immunoreactivity in the plasma during ictal and interictal periods of migraine patients. Cephalalgia, 2013, 33(13), 1085-1095.
[] [PMID: 23598374]
Cernuda-Morollón, E.; Riesco, N.; Martínez-Camblor, P.; Serrano-Pertierra, E.; García-Cabo, C.; Pascual, J. No change in interictal PACAP levels in peripheral blood in women with chronic migraine. Headache, 2016, 56(9), 1448-1454.
[] [PMID: 27634731]
Tuka, B.; Szabó, N.; Tóth, E.; Kincses, Z.T.; Párdutz, Á.; Szok, D.; Körtési, T.; Bagoly, T.; Helyes, Z.; Edvinsson, L.; Vécsei, L.; Tajti, J. Release of PACAP-38 in episodic cluster headache patients - an exploratory study. J. Headache Pain, 2016, 17(1), 69.
[] [PMID: 27475101]
Han, X.; Dong, Z.; Hou, L.; Wan, D.; Chen, M.; Tang, W.; Yu, S. Interictal plasma pituitary adenylate cyclase-activating polypeptide levels are decreased in migraineurs but remain unchanged in patients with tension-type headache. Clin. Chim. Acta, 2015, 450, 151-154.
[] [PMID: 26296898]
Covelli, V.; Massari, F.; Fallacara, C.; Munno, I.; Pellegrino, N.M.; Jirillo, E.; Savastano, S.; Ghiggi, M.R.; Tommaselli, A.P.; Lombardi, G. Increased spontaneous release of tumor necrosis factor-alpha/cachectin in headache patients. A possible correlation with plasma endotoxin and hypothalamic-pituitary-adrenal axis. Int. J. Neurosci., 1991, 61(1-2), 53-60.
[] [PMID: 1667186]
Kaciński, M.; Gergont, A.; Kubik, A.; Steczkowska-Klucznik, M. [Proinflammatory cytokines in children with migraine with or without aura Przegl. Lek., 2005, 62(11), 1276-1280.
[PMID: 16512620]
Perini, F.; D’Andrea, G.; Galloni, E.; Pignatelli, F.; Billo, G.; Alba, S.; Bussone, G.; Toso, V. Plasma cytokine levels in migraineurs and controls. Headache, 2005, 45(7), 926-931.
[] [PMID: 15985111]
Sarchielli, P.; Alberti, A.; Baldi, A.; Coppola, F.; Rossi, C.; Pierguidi, L.; Floridi, A.; Calabresi, P. Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally. Headache, 2006, 46(2), 200-207.
[] [PMID: 16492228]
Rozen, T.; Swidan, S.Z. Elevation of CSF tumor necrosis factor alpha levels in new daily persistent headache and treatment refractory chronic migraine. Headache, 2007, 47(7), 1050-1055.
[] [PMID: 17635596]
Boćkowski, L.; Sobaniec, W.; Zelazowska-Rutkowska, B. Proinflammatory plasma cytokines in children with migraine. Pediatr. Neurol., 2009, 41(1), 17-21.
[] [PMID: 19520268]
Hirfanoglu, T.; Serdaroglu, A.; Gulbahar, O.; Cansu, A. Prophylactic drugs and cytokine and leptin levels in children with migraine. Pediatr. Neurol., 2009, 41(4), 281-287.
[] [PMID: 19748048]
Koçer, A.; Memişoğullari, R.; Domaç, F.M.; Ilhan, A.; Koçer, E.; Okuyucu, S.; Ozdemir, B.; Yüksel, H. IL-6 levels in migraine patients receiving topiramate. Pain Pract., 2009, 9(5), 375-379.
[] [PMID: 19622115]
Wang, F.; He, Q.; Ren, Z.; Li, F.; Chen, W.; Lin, X.; Zhang, H.; Tai, G. Association of serum levels of intercellular adhesion molecule-1 and interleukin-6 with migraine. Neurol. Sci., 2015, 36(4), 535-540.
[] [PMID: 25417066]
Uzar, E.; Evliyaoglu, O.; Yucel, Y.; Ugur Cevik, M.; Acar, A.; Guzel, I.; Islamoglu, Y.; Colpan, L.; Tasdemir, N. Serum cytokine and pro-brain natriuretic peptide (BNP) levels in patients with migraine. Eur. Rev. Med. Pharmacol. Sci., 2011, 15(10), 1111-1116.
[PMID: 22165670]
Yücel, M.; Kotan, D.; Gurol Çiftçi, G.; Çiftçi, I.H.; Cikriklar, H.I. Serum levels of endocan, claudin-5 and cytokines in migraine. Eur. Rev. Med. Pharmacol. Sci., 2016, 20(5), 930-936.
[PMID: 27010153]
Covelli, V.; Munno, I.; Pellegrino, N.M.; Marinaro, M.R.; Gesario, A.; Massari, F.; Savastano, S.; Jirillo, E. In vivo administration of propranolol decreases exaggerated amounts of serum TNF-alpha in patients with migraine without aura. Possible mechanism of action. Acta Neurol. (Napoli), 1992, 14(4-6), 313-319.
[PMID: 1293974]
Dahri, M.; Tarighat-Esfanjani, A.; Asghari-Jafarabadi, M.; Hashemilar, M. Oral coenzyme Q10 supplementation in patients with migraine: Effects on clinical features and inflammatory markers. Nutr. Neurosci., 2018, 3, 1-9.
[] [PMID: 29298622]
Abdolahi, M.; Tafakhori, A.; Togha, M.; Okhovat, A.A.; Siassi, F.; Eshraghian, M.R.; Sedighiyan, M.; Djalali, M.; Mohammadzadeh Honarvar, N.; Djalali, M. The synergistic effects of ω-3 fatty acids and nano-curcumin supplementation on tumor necrosis factor (TNF)-α gene expression and serum level in migraine patients. Immunogenetics, 2017, 69(6), 371-378.
[] [PMID: 28478481]
Vanmolkot, F.H.; de Hoon, J.N. Increased C-reactive protein in young adult patients with migraine. Cephalalgia, 2007, 27(7), 843-846.
[] [PMID: 17668468]
Kurth, T.; Ridker, P.M.; Buring, J.E. Migraine and biomarkers of cardiovascular disease in women. Cephalalgia, 2008, 28(1), 49-56.
[] [PMID: 17986270]
Tietjen, G.E.; Herial, N.A.; White, L.; Utley, C.; Kosmyna, J.M.; Khuder, S.A. Migraine and biomarkers of endothelial activation in young women. Stroke, 2009, 40(9), 2977-2982.
[] [PMID: 19608996]
Bigal, M.E.; Kurth, T.; Hu, H.; Santanello, N.; Lipton, R.B. Migraine and cardiovascular disease: possible mechanisms of interaction. Neurology, 2009, 72(21), 1864-1871.
[] [PMID: 19470970]
Nelson, K.B.; Richardson, A.K.; He, J.; Lateef, T.M.; Khoromi, S.; Merikangas, K.R. Headache and biomarkers predictive of vascular disease in a representative sample of US children. Arch. Pediatr. Adolesc. Med., 2010, 164(4), 358-362.
[] [PMID: 20368489]
Güzel, I.; Taşdemir, N.; Celik, Y. Evaluation of serum transforming growth factor β1 and C-reactive protein levels in migraine patients. Neurol. Neurochir. Pol., 2013, 47(4), 357-362.
[] [PMID: 23986426]
Tanik, N.; Celikbilek, A.; Metin, A.; Gocmen, A.Y.; Inan, L.E. Retinol-binding protein-4 and hs-CRP levels in patients with migraine. Neurol. Sci., 2015, 36(10), 1823-1827.
[] [PMID: 26012852]
Avci, A.Y.; Lakadamyali, H.; Arikan, S.; Benli, U.S.; Kilinc, M. High sensitivity C-reactive protein and cerebral white matter hyperintensities on magnetic resonance imaging in migraine patients. J. Headache Pain, 2015, 16, 9.
[] [PMID: 25595197]
Peng, Y.F.; Xie, L.Q.; Xiang, Y.; Xu, G.D. Serum Bilirubin and Their Association With C-Reactive Protein in Patients With Migraine. J. Clin. Lab. Anal., 2016, 30(6), 982-985.
[] [PMID: 26996761]
Theodoropoulos, D.S.; Katzenberger, D.R.; Jones, W.M.; Morris, D.L.; Her, C.; Cullen, N.A.; Morrisa, D.L. Allergen-specific sublingual immunotherapy in the treatment of migraines: a prospective study. Eur. Rev. Med. Pharmacol. Sci., 2011, 15(10), 1117-1121.
[PMID: 22165671]
Guldiken, S.; Guldiken, B.; Demir, M.; Kabayel, L.; Ozkan, H.; Turgut, N.; Hunkar, R.; Kat, S. Soluble CD40 ligand and prolactin levels in migraine patients during interictal period. J. Headache Pain, 2011, 12(3), 355-360.
[] [PMID: 21331754]
Fava, A.; Pirritano, D.; Consoli, D.; Plastino, M.; Casalinuovo, F.; Cristofaro, S.; Colica, C.; Ermio, C.; De Bartolo, M.; Opipari, C.; Lanzo, R.; Consoli, A.; Bosco, D. Chronic migraine in women is associated with insulin resistance: a cross-sectional study. Eur. J. Neurol., 2014, 21(2), 267-272.
[] [PMID: 24238370]
Poyrazoglu, H.G.; Vurdem, U.E.; Arslan, A.; Uytun, S. Evaluation of carotid intima-media thickness in children with migraine: a marker of subclinical atherosclerosis. Neurol. Sci., 2016, 37(10), 1663-1669.
[] [PMID: 27371188]
Ceylan, M.; Bayraktutan, O.F.; Becel, S.; Atis, Ö.; Yalcin, A.; Kotan, D. Serum levels of pentraxin-3 and other inflammatory biomarkers in migraine: Association with migraine characteristics. Cephalalgia, 2016, 36(6), 518-525.
[] [PMID: 26243757]
Scher, A.I.; Stewart, W.F.; Ricci, J.A.; Lipton, R.B. Factors associated with the onset and remission of chronic daily headache in a population-based study. Pain, 2003, 106(1-2), 81-89.
[] [PMID: 14581114]
Bigal, M.E.; Lipton, R.B. Obesity is a risk factor for transformed migraine but not chronic tension-type headache. Neurology, 2006, 67(2), 252-257.
[] [PMID: 16864817]
Peterlin, B.L.; Rosso, A.L.; Rapoport, A.M.; Scher, A.I. Obesity and migraine: the effect of age, gender and adipose tissue distribution. Headache, 2010, 50(1), 52-62.
[] [PMID: 19496830]
Peterlin, B.L.; Rosso, A.L.; Williams, M.A.; Rosenberg, J.R.; Haythornthwaite, J.A.; Merikangas, K.R.; Gottesman, R.F.; Bond, D.S.; He, J.P.; Zonderman, A.B. Episodic migraine and obesity and the influence of age, race, and sex. Neurology, 2013, 81(15), 1314-1321.
[] [PMID: 24027060]
Peterlin, B.L.; Sacco, S.; Bernecker, C.; Scher, A.I. Adipokines and migraine: A systematic review. Headache, 2016, 56(4), 622-644.
[] [PMID: 27012149]
Ferroni, P.; Barbanti, P.; Della-Morte, D.; Palmirotta, R.; Jirillo, E.; Guadagni, F. Redox mechanisms in migraine: novel therapeutics and dietary interventions. Antioxid. Redox Signal., 2018, 28(12), 1144-1183.
[] [PMID: 28990418]
Chai, N.C.; Gelaye, B.; Tietjen, G.E.; Dash, P.D.; Gower, B.A.; White, L.W.; Ward, T.N.; Scher, A.I.; Peterlin, B.L. Ictal adipokines are associated with pain severity and treatment response in episodic migraine. Neurology, 2015, 84(14), 1409-1418.
[] [PMID: 25746563]
Peterlin, B.L.; Bigal, M.E.; Tepper, S.J.; Urakaze, M.; Sheftell, F.D.; Rapoport, A.M. Migraine and adiponectin: is there a connection? Cephalalgia, 2007, 27(5), 435-446.
[] [PMID: 17448181]
Peterlin, B.L.; Alexander, G.; Tabby, D.; Reichenberger, E. Oligomerization state-dependent elevations of adiponectin in chronic daily headache. Neurology, 2008, 70(20), 1905-1911.
[] [PMID: 18474846]
Peterlin, B.L.; Tietjen, G.E.; Gower, B.A.; Ward, T.N.; Tepper, S.J.; White, L.W.; Dash, P.D.; Hammond, E.R.; Haythornthwaite, J.A. Ictal adiponectin levels in episodic migraineurs: a randomized pilot trial. Headache, 2013, 53(3), 474-490.
[] [PMID: 23489216]
Duarte, H.; Teixeira, A.L.; Rocha, N.P.; Domingues, R.B. Increased serum levels of adiponectin in migraine. J. Neurol. Sci., 2014, 342(1-2), 186-188.
[] [PMID: 24819919]
Dearborn, J.L.; Schneider, A.L.; Gottesman, R.F.; Kurth, T.; Pankow, J.S.; Couper, D.J.; Rose, K.M.; Williams, M.A.; Peterlin, B.L. Adiponectin and leptin levels in migraineurs in the atherosclerosis risk in communities study. Neurology, 2014, 83(24), 2211-2218.
[] [PMID: 25378672]
Rubino, E.; Vacca, A.; Govone, F.; Gai, A.; Boschi, S.; Zucca, M.; De Martino, P.; Gentile, S.; Pinessi, L.; Rainero, I. Investigating the role of adipokines in chronic migraine. Cephalalgia, 2017, 37(11), 1067-1073.
[] [PMID: 27553954]
Dominguez, C.; Vieites-Prado, A.; Perez-Mato, M.; Sobrino, T.; Rodriguez-Osorio, X.; Lopez, A.; Campos, F.; Martinez, F.; Castillo, J.; Leira, R. Role of adipocytokines in the pathophysiology of migraine: A cross-sectional study. Cephalalgia, 2018, 38(5), 1005-1006.
[] [PMID: 29034787]
Bernecker, C.; Pailer, S.; Kieslinger, P.; Horejsi, R.; Möller, R.; Lechner, A.; Wallner-Blazek, M.; Weiss, S.; Fazekas, F.; Truschnig-Wilders, M.; Gruber, H.J. GLP-2 and leptin are associated with hyperinsulinemia in non-obese female migraineurs. Cephalalgia, 2010, 30(11), 1366-1374.
[] [PMID: 20959431]
Pisanu, C.; Preisig, M.; Castelao, E.; Glaus, J.; Cunningham, J.L.; Del Zompo, M.; Merikangas, K.R.; Schiöth, H.B.; Mwinyi, J. High leptin levels are associated with migraine with aura. Cephalalgia, 2017, 37(5), 435-441.
[] [PMID: 27165492]
Ligong, Z.; Jinjin, Q.; Chunfu, C.; Congcong, L.; Xiaojun, D. Effect of obesity and leptin level on migraineurs. Med. Sci. Monit., 2015, 21, 3270-3274.
[] [PMID: 26508370]
Guldiken, B.; Guldiken, S.; Demir, M.; Turgut, N.; Tugrul, A. Low leptin levels in migraine: a case control study. Headache, 2008, 48(7), 1103-1107.
[] [PMID: 18547265]
Bonetti, P.O.; Lerman, L.O.; Lerman, A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler. Thromb. Vasc. Biol., 2003, 23(2), 168-175.
[] [PMID: 12588755]
Carolei, A.; Marini, C.; De Matteis, G. History of migraine and risk of cerebral ischaemia in young adults. Lancet, 1996, 347(9014), 1503-1506.
[] [PMID: 8684100]
Kurth, T.; Schürks, M.; Logroscino, G.; Buring, J.E. Migraine frequency and risk of cardiovascular disease in women. Neurology, 2009, 73(8), 581-588.
[] [PMID: 19553594]
Kurth, T.; Winter, A.C.; Eliassen, A.H.; Dushkes, R.; Mukamal, K.J.; Rimm, E.B.; Willett, W.C.; Manson, J.E.; Rexrode, K.M. Migraine and risk of cardiovascular disease in women: prospective cohort study. BMJ, 2016, 353, i2610.
[] [PMID: 27247281]
Adelborg, K.; Szépligeti, S.K.; Holland-Bill, L.; Ehrenstein, V.; Horváth-Puhó, E.; Henderson, V.W.; Sørensen, H.T. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. BMJ, 2018, 360, k96.
[] [PMID: 29386181]
Kruit, M.C.; Launer, L.J.; Ferrari, M.D.; van Buchem, M.A. Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study. Brain, 2005, 128(Pt 9), 2068-2077.
[] [PMID: 16006538]
González-Quintanilla, V.; Toriello, M.; Palacio, E.; González-Gay, M.A.; Castillo, J.; Montes, S.; Martínez-Nieto, R.; Fernandez, J.; Rojo, A.; Gutiérrez, S.; Pons, E.; Oterino, A. Systemic and cerebral endothelial dysfunction in chronic migraine. A case-control study with an active comparator. Cephalalgia, 2016, 36(6), 552-560.
[] [PMID: 26395894]
Larsen, J.S.; Skaug, E.A.; Wisløff, U.; Ellingsen, Ø.; Stovner, L.J.; Linde, M.; Hagen, K. Migraine and endothelial function: The HUNT3 Study. Cephalalgia, 2016, 36(14), 1341-1349.
[] [PMID: 26868818]
Rajan, R.; Khurana, D.; Lal, V. Interictal cerebral and systemic endothelial dysfunction in patients with migraine: a case-control study. J. Neurol. Neurosurg. Psychiatry, 2015, 86(11), 1253-1257.
[] [PMID: 25550413]
Hamed, S.A.; Hamed, E.A.; Ezz Eldin, A.M.; Mahmoud, N.M. Vascular risk factors, endothelial function, and carotid thickness in patients with migraine: relationship to atherosclerosis. J. Stroke Cerebrovasc. Dis., 2010, 19(2), 92-103.
[] [PMID: 20189084]
Gallai, V.; Sarchielli, P.; Firenze, C.; Trequattrini, A.; Paciaroni, M.; Usai, F.; Palumbo, R. Endothelin 1 in migraine and tension-type headache. Acta Neurol. Scand., 1994, 89(1), 47-55.
[] [PMID: 8178628]
Hasselblatt, M.; Köhler, J.; Volles, E.; Ehrenreich, H. Simultaneous monitoring of endothelin-1 and vasopressin plasma levels in migraine. Neuroreport, 1999, 10(2), 423-425.
[] [PMID: 10203347]
Kallela, M.; Färkkilä, M.; Saijonmaa, O.; Fyhrquist, F. Endothelin in migraine patients. Cephalalgia, 1998, 18(6), 329-332.
[] [PMID: 9731937]
Färkkilä, M.; Palo, J.; Saijonmaa, O.; Fyhrquist, F. Raised plasma endothelin during acute migraine attack. Cephalalgia, 1992, 12(6), 383-384.
[] [PMID: 1341430]
Nattero, G.; Mengozzi, G.; Inconis, T.; Paradisi, L. Nitric oxide, endothelin-1, and transcranial Doppler in migraine. Findings in interictal conditions and during migraine attack. Headache, 1996, 36(5), 307-311.
[] [PMID: 8682672]
Guldiken, B.; Demir, M.; Guldiken, S.; Turgut, N.; Ozkan, H.; Kabayel, L.; Tugrul, A. Asymmetric dimethylarginine and nitric oxide levels in migraine during the interictal period. J. Clin. Neurosci., 2009, 16(5), 672-674.
[] [PMID: 19282179]
Uzar, E.; Evliyaoglu, O.; Toprak, G.; Acar, A.; Yucel, Y.; Calisir, T.; Cevik, M.U.; Tasdemir, N. Increased asymmetric dimethylarginine and nitric oxide levels in patients with migraine. J. Headache Pain, 2011, 12(2), 239-243.
[] [PMID: 21359872]
Erdélyi-Bótor, S.; Komáromy, H.; Kamson, D.O.; Kovács, N.; Perlaki, G.; Orsi, G.; Molnár, T.; Illes, Z.; Nagy, L.; Kéki, S.; Deli, G.; Bosnyák, E.; Trauninger, A.; Pfund, Z. Serum L-arginine and dimethylarginine levels in migraine patients with brain white matter lesions. Cephalalgia, 2017, 37(6), 571-580.
[] [PMID: 27206959]
Cesar, J.M.; García-Avello, A.; Vecino, A.M.; Sastre, J.L.; Alvarez-Cermeño, J.C. Increased levels of plasma von Willebrand factor in migraine crisis. Acta Neurol. Scand., 1995, 91(5), 412-413.
[] [PMID: 7639074]
Tietjen, G.E.; Al-Qasmi, M.M.; Athanas, K.; Dafer, R.M.; Khuder, S.A. Increased von Willebrand factor in migraine. Neurology, 2001, 57(2), 334-336.
[] [PMID: 11468324]
Tietjen, G.E.; Al-Qasmi, M.M.; Athanas, K.; Utley, C.; Herial, N.A. Altered hemostasis in migraineurs studied with a dynamic flow system. Thromb. Res., 2007, 119(2), 217-222.
[] [PMID: 16504253]
Tietjen, G.E.; Khubchandani, J.; Herial, N.; Palm-Meinders, I.H.; Koppen, H.; Terwindt, G.M.; van Buchem, M.A.; Launer, L.J.; Ferrari, M.D.; Kruit, M.C. Migraine and vascular disease biomarkers: A population-based case-control study. Cephalalgia, 2018, 38(3), 511-518.
[] [PMID: 28885052]
Ferroni, P.; Barbanti, P.; Aurilia, C.; Egeo, G.; Fofi, L.; La Farina, F.; Valente, M.G.; De Marchis, M.L.; Spila, A.; Palmirotta, R.; Della-Morte, D.; Guadagni, F. Procoagulant imbalance in premenopausal women with chronic migraine. Neurology, 2017, 89(14), 1525-1527.
[] [PMID: 28842452]
Michalak, S.; Kalinowska-Lyszczarz, A.; Wegrzyn, D.; Thielemann, A.; Osztynowicz, K.; Kozubski, W. The levels of circulating proangiogenic factors in migraineurs. Neuromolecular Med., 2017, 19(4), 510-517.
[] [PMID: 28918499]
Chironi, G.N.; Boulanger, C.M.; Simon, A.; Dignat-George, F.; Freyssinet, J.M.; Tedgui, A. Endothelial microparticles in diseases. Cell Tissue Res., 2009, 335(1), 143-151.
[] [PMID: 18989704]
Liman, T.G.; Bachelier-Walenta, K.; Neeb, L.; Rosinski, J.; Reuter, U.; Böhm, M.; Endres, M. Circulating endothelial microparticles in female migraineurs with aura. Cephalalgia, 2015, 35(2), 88-94.
[] [PMID: 24715500]
Lee, S.T.; Chu, K.; Jung, K.H.; Kim, D.H.; Kim, E.H.; Choe, V.N.; Kim, J.H.; Im, W.S.; Kang, L.; Park, J.E.; Park, H.J.; Park, H.K.; Song, E.C.; Lee, S.K.; Kim, M.; Roh, J.K. Decreased number and function of endothelial progenitor cells in patients with migraine. Neurology, 2008, 70(17), 1510-1517.
[] [PMID: 18354079]
Rodríguez-Osorio, X.; Sobrino, T.; Brea, D.; Martínez, F.; Castillo, J.; Leira, R. Endothelial progenitor cells: a new key for endothelial dysfunction in migraine. Neurology, 2012, 79(5), 474-479.
[] [PMID: 22815557]
Oterino, A.; Toriello, M.; Palacio, E.; Quintanilla, V.G.; Ruiz-Lavilla, N.; Montes, S.; Vega, M.S.; Martinez-Nieto, R.; Castillo, J.; Pascual, J. Analysis of endothelial precursor cells in chronic migraine: a case-control study. Cephalalgia, 2013, 33(4), 236-244.
[] [PMID: 23223547]
Cheng, C.Y.; Chen, S.P.; Liao, Y.C.; Fuh, J.L.; Wang, Y.F.; Wang, S.J. Elevated circulating endothelial-specific microRNAs in migraine patients: A pilot study. Cephalalgia, 2018, 38(9), 1585-1591.
[] [PMID: 29126355]
Blann, A.D. Plasma von Willebrand factor, thrombosis, and the endothelium: the first 30 years. Thromb. Haemost., 2006, 95(1), 49-55.
[] [PMID: 16543961]
Marder, V.J.; Aird, W.; Bennett, J.S.; Schulman, S.; White, G.C., II Hemostasis and thrombosis. Basic principles and clinical practice, (6th ed. ),; Lippincott Williams & Wilkins, 2012.
Bongers, T.N.; de Maat, M.P.; van Goor, M.L.; Bhagwanbali, V.; van Vliet, H.H.; Gómez García, E.B.; Dippel, D.W.; Leebeek, F.W. High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, inflammation, and genetic variability. Stroke, 2006, 37(11), 2672-2677.
[] [PMID: 16990571]
Spencer, C.G.; Felmeden, D.C.; Blann, A.D.; Lip, G.Y. Haemorheological, platelet and endothelial indices in relation to global measures of cardiovascular risk in hypertensive patients: a substudy of the Anglo-Scandinavian cardiac outcomes trial. J. Intern. Med., 2007, 261(1), 82-90.
[] [PMID: 17222171]
Qizilbash, N.; Duffy, S.; Prentice, C.R.; Boothby, M.; Warlow, C. Von Willebrand factor and risk of ischemic stroke. Neurology, 1997, 49(6), 1552-1556.
[] [PMID: 9409345]
Folsom, A.R.; Rosamond, W.D.; Shahar, E.; Cooper, L.S.; Aleksic, N.; Nieto, F.J.; Rasmussen, M.L.; Wu, K.K. Prospective study of markers of hemostatic function with risk of ischemic stroke. Circulation, 1999, 100(7), 736-742.
[] [PMID: 10449696]
O’Donnell, J.; Boulton, F.E.; Manning, R.A.; Laffan, M.A. Amount of H antigen expressed on circulating von Willebrand factor is modified by ABO blood group genotype and is a major determinant of plasma von Willebrand factor antigen levels. Arterioscler. Thromb. Vasc. Biol., 2002, 22(2), 335-341.
[] [PMID: 11834538]
Tafuri, E.; Santovito, D.; de Nardis, V.; Marcantonio, P.; Paganelli, C.; Affaitati, G.; Bucci, M.; Mezzetti, A.; Giamberardino, M.A.; Cipollone, F. MicroRNA profiling in migraine without aura: pilot study. Ann. Med., 2015, 47(6), 468-473.
[] [PMID: 26333279]
Andersen, H.H.; Duroux, M.; Gazerani, P. Serum MicroRNA signatures in migraineurs during attacks and in pain-free periods. Mol. Neurobiol., 2016, 53(3), 1494-1500.
[] [PMID: 25636687]
Gallelli, L.; Cione, E.; Caroleo, M.C.; Carotenuto, M.; Lagana, P.; Siniscalchi, A.; Guidetti, V. microRNAs to monitor pain-migraine and drug treatment. MicroRNA, 2017, 6(3), 152-156.
[] [PMID: 28901847]
Gallelli, L.; Siniscalchi, A.; Carotenuto, M.; Caroleo, M.C.; Cione, E.; Guidetti, V. microRNAs-based predictor factor in patients with migraine-ischemic stroke. MicroRNA, 2017, 6(1), 17-21.
[] [PMID: 28056747]
Imamura, K.; Takeshima, T.; Fusayasu, E.; Nakashima, K. Increased plasma matrix metalloproteinase-9 levels in migraineurs. Headache, 2008, 48(1), 135-139.
[] [PMID: 18005141]
Durham, P.; Papapetropoulos, S. Biomarkers associated with migraine and their potential role in migraine management. Headache, 2013, 53(8), 1262-1277.
[] [PMID: 23848170]
Ishizaki, K.; Takeshima, T.; Fukuhara, Y.; Araki, H.; Nakaso, K.; Kusumi, M.; Nakashima, K. Increased plasma transforming growth factor-beta1 in migraine. Headache, 2005, 45(9), 1224-1228.
[] [PMID: 16178953]
Gursoy-Ozdemir, Y.; Qiu, J.; Matsuoka, N.; Bolay, H.; Bermpohl, D.; Jin, H.; Wang, X.; Rosenberg, G.A.; Lo, E.H.; Moskowitz, M.A. Cortical spreading depression activates and upregulates MMP-9. J. Clin. Invest., 2004, 113(10), 1447-1455.
[] [PMID: 15146242]
Nagata, E.; Hattori, H.; Kato, M.; Ogasawara, S.; Suzuki, S.; Shibata, M.; Shimizu, T.; Hamada, J.; Osada, T.; Takaoka, R.; Kuwana, M.; Tsunoda, T.; Aiso, S.; Takizawa, S.; Suzuki, N.; Takagi, S. Identification of biomarkers associated with migraine with aura. Neurosci. Res., 2009, 64(1), 104-110.
[] [PMID: 19428688]
Yuasa, N.; Nagata, E.; Fujii, N.; Ito, M.; Tsukamoto, H.; Takizawa, S. Serum apolipoprotein E may be a novel biomarker of migraine. PLoS One, 2018, 13(1)e0190620
[] [PMID: 29357368]
Sargent, D.J.; Mandrekar, S.J. Statistical issues in the validation of prognostic, predictive, and surrogate biomarkers. Clin. Trials, 2013, 10(5), 647-652.
[] [PMID: 23983158]
Ramón, C.; Cernuda-Morollón, E.; Pascual, J. Calcitonin gene-related peptide in peripheral blood as a biomarker for migraine. Curr. Opin. Neurol., 2017, 30(3), 281-286.
[] [PMID: 28234796]
Headache Classification Committee of the International Headache Society (IHS) In: The international classification of headache disorders; 3rd Edition (beta version). Cephalalgia. , 2013; 33, pp. 629-808.
[] [PMID: 23771276]
Barbanti, P.; Fabbrini, G.; Pesare, M.; Vanacore, N.; Cerbo, R. Unilateral cranial autonomic symptoms in migraine. Cephalalgia, 2002, 22(4), 256-259.
[] [PMID: 12100086]
Barbanti, P.; Fofi, L.; Dall’Armi, V.; Aurilia, C.; Egeo, G.; Vanacore, N.; Bonassi, S. Rizatriptan in migraineurs with unilateral cranial autonomic symptoms: a double-blind trial. J. Headache Pain, 2012, 13(5), 407-414.
[] [PMID: 22460943]
Obermann, M.; Yoon, M.S.; Dommes, P.; Kuznetsova, J.; Maschke, M.; Weimar, C.; Limmroth, V.; Diener, H.C.; Katsarava, Z. Prevalence of trigeminal autonomic symptoms in migraine: a population-based study. Cephalalgia, 2007, 27(6), 504-509.
[] [PMID: 17428298]
Barbanti, P.; Egeo, G. Pharmacological trials in migraine: it’s time to reappraise where the headache is and what the pain is like. Headache, 2015, 55(3), 439-441.
[] [PMID: 25523108]
Barbanti, P.; Fabbrini, G.; Vanacore, N.; Pesare, M.; Buzzi, M.G. Sumatriptan in migraine with unilateral cranial autonomic symptoms: an open study. Headache, 2003, 43(4), 400-403.
[] [PMID: 12656712]
Blau, J.N. The clinical diagnosis of migraine: the beginning of therapy. J. Neurol., 1991, 238(Suppl. 1), S6-S11.
[] [PMID: 2045833]
Barbanti, P.; Ferroni, P. Onabotulinum toxin A in the treatment of chronic migraine: patient selection and special considerations. J. Pain Res., 2017, 10, 2319-2329.
[] [PMID: 29033605]

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Year: 2019
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DOI: 10.2174/0929867325666180622122938
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