Top

The Journal of Headache and Pain

Published in:

Open Access 01-12-2021 | Migraine | Review article

Migraine and neuroinflammation: the inflammasome perspective

Authors: Oguzhan Kursun, Muge Yemisci, Arn M. J. M. van den Maagdenberg, Hulya Karatas

Published in: The Journal of Headache and Pain | Issue 1/2021

Abstract

Background

Neuroinflammation has an important role in the pathophysiology of migraine, which is a complex neuro-glio-vascular disorder. The main aim of this review is to highlight findings of cortical spreading depolarization (CSD)-induced neuroinflammatory signaling in brain parenchyma from the inflammasome perspective. In addition, we discuss the limited data of the contribution of inflammasomes to other aspects of migraine pathophysiology, foremost the activation of the trigeminovascular system and thereby the generation of migraine pain.

Main body

Inflammasomes are signaling multiprotein complexes and key components of the innate immune system. Their activation causes the production of inflammatory cytokines that can stimulate trigeminal neurons and are thus relevant to the generation of migraine pain. The contribution of inflammasome activation to pain signaling has attracted considerable attention in recent years. Nucleotide-binding domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) is the best characterized inflammasome and there is emerging evidence of its role in a variety of inflammatory pain conditions, including migraine. In this review, we discuss, from an inflammasome point of view, cortical spreading depolarization (CSD)-induced neuroinflammatory signaling in brain parenchyma, the connection with genetic factors that make the brain vulnerable to CSD, and the relation of the inflammasome with diseases that are co-morbid with migraine, including stroke, epilepsy, and the possible links with COVID-19 infection.

Conclusion

Neuroinflammatory pathways, specifically those involving inflammasome proteins, seem promising candidates as treatment targets, and perhaps even biomarkers, in migraine.

Headache Classification Committee of the International Headache Society (IHS) (2018) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38(1):1–211CrossRef

Collaborators GeBDH (2018) Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol 17(11):954–976CrossRef

Buse DC, Loder EW, Gorman JA, Stewart WF, Reed ML, Fanning KM, Serrano D, Lipton RB (2013) Sex differences in the prevalence, symptoms, and associated features of migraine, probable migraine and other severe headache: results of the American Migraine Prevalence and Prevention (AMPP) study. Headache. 53(8):1278–1299. https://doi.org/10.1111/head.12150CrossRefPubMed

Messali A, Sanderson JC, Blumenfeld AM, Goadsby PJ, Buse DC, Varon SF et al (2016) Direct and indirect costs of chronic and episodic migraine in the United States: a web-based survey. Headache. 56(2):306–322PubMedCrossRef

Gilhus NE, Deuschl G (2019) Neuroinflammation - a common thread in neurological disorders. Nat Rev Neurol 15(8):429–430. https://doi.org/10.1038/s41582-019-0227-8CrossRefPubMed

Edvinsson L, Haanes KA, Warfvinge K (2019) Does inflammation have a role in migraine? Nat Rev Neurol 15(8):483–490. https://doi.org/10.1038/s41582-019-0216-yCrossRefPubMed

Walsh JG, Muruve DA, Power C (2014) Inflammasomes in the CNS. Nat Rev Neurosci 15(2):84–97. https://doi.org/10.1038/nrn3638CrossRefPubMed

Noseda R, Burstein R (2013) Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain. 154(Suppl 1):S44–S53. https://doi.org/10.1016/j.pain.2013.07.021CrossRefPubMed

Ferrari MD, Klever RR, Terwindt GM, Ayata C, van den Maagdenberg AM (2015) Migraine pathophysiology: lessons from mouse models and human genetics. Lancet Neurol 14(1):65–80. https://doi.org/10.1016/S1474-4422(14)70220-0CrossRefPubMed

10.

Pietrobon D, Moskowitz MA (2013) Pathophysiology of migraine. Annu Rev Physiol 75(1):365–391. https://doi.org/10.1146/annurev-physiol-030212-183717CrossRefPubMed

11.

Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S (2017) Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev 97(2):553–622. https://doi.org/10.1152/physrev.00034.2015CrossRefPubMedPubMedCentral

12.

Levy D (2012) Endogenous mechanisms underlying the activation and sensitization of meningeal nociceptors: the role of immuno-vascular interactions and cortical spreading depression. Curr Pain Headache Rep 16(3):270–277. https://doi.org/10.1007/s11916-012-0255-1CrossRefPubMed

13.

Bruno PP, Carpino F, Carpino G, Zicari A (2007) An overview on immune system and migraine. Eur Rev Med Pharmacol Sci 11(4):245–248PubMed

14.

Perini F, D'Andrea G, Galloni E, Pignatelli F, Billo G, Alba S, Bussone G, Toso V (2005) Plasma cytokine levels in migraineurs and controls. Headache. 45(7):926–931. https://doi.org/10.1111/j.1526-4610.2005.05135.xCrossRefPubMed

15.

Aydin M, Demir CF, Arikanoglu A, Bulut S, Ilhan N (2015) Plasma cytokine levels in Migraineurs during and outside of attacks. Eur J Gen Med 12(4):307–312

16.

Yilmaz IA, Ozge A, Erdal ME, Edgunlu TG, Cakmak SE, Yalin OO (2010) Cytokine polymorphism in patients with migraine: some suggestive clues of migraine and inflammation. Pain Med 11(4):492–497PubMedCrossRef

17.

Ayata C, Lauritzen M (2015) Spreading depression, spreading depolarizations, and the cerebral vasculature. Physiol Rev 95(3):953–993. https://doi.org/10.1152/physrev.00027.2014CrossRefPubMedPubMedCentral

18.

Charles AC, Baca SM (2013) Cortical spreading depression and migraine. Nat Rev Neurol 9(11):637–644. https://doi.org/10.1038/nrneurol.2013.192CrossRefPubMed

19.

Leao AA (1951) The slow voltage variation of cortical spreading depression of activity. Electroencephalogr Clin Neurophysiol 3(3):315–321. https://doi.org/10.1016/0013-4694(51)90079-XCrossRefPubMed

20.

Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA (2002) Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 8(2):136–142. https://doi.org/10.1038/nm0202-136CrossRefPubMed

21.

Zhang X, Levy D, Noseda R, Kainz V, Jakubowski M, Burstein R (2010) Activation of meningeal nociceptors by cortical spreading depression: implications for migraine with aura. J Neurosci 30(26):8807–8814PubMedPubMedCentralCrossRef

22.

Thompson CS, Hakim AM (2005) Cortical spreading depression modifies components of the inflammatory cascade. Mol Neurobiol 32(1):51–57PubMedCrossRef

23.

Karatas H, Erdener SE, Gursoy-Ozdemir Y, Lule S, Eren-Kocak E, Sen ZD, Dalkara T (2013) Spreading depression triggers headache by activating neuronal Panx1 channels. Science. 339(6123):1092–1095. https://doi.org/10.1126/science.1231897CrossRefPubMed

24.

Chen SP, Qin T, Seidel JL, Zheng Y, Eikermann M, Ferrari MD, van den Maagdenberg AMJM, Moskowitz MA, Ayata C, Eikermann-Haerter K (2017) Inhibition of the P2X7-PANX1 complex suppresses spreading depolarization and neuroinflammation. Brain. 140(6):1643–1656. https://doi.org/10.1093/brain/awx085CrossRefPubMedPubMedCentral

25.

Takizawa T, Qin T, Lopes de Morais A, Sugimoto K, Chung JY, Morsett L et al (2020) Non-invasively triggered spreading depolarizations induce a rapid pro-inflammatory response in cerebral cortex. J Cereb Blood Flow Metab 40(5):1117–1131PubMedCrossRef

26.

Ghaemi A, Alizadeh L, Babaei S, Jafarian M, Khaleghi Ghadiri M, Meuth SG, Kovac S, Gorji A (2018) Astrocyte-mediated inflammation in cortical spreading depression. Cephalalgia. 38(4):626–638. https://doi.org/10.1177/0333102417702132CrossRefPubMed

27.

Takizawa T, Shibata M, Kayama Y, Toriumi H, Ebine T, Koh A, Shimizu T, Suzuki N (2016) Temporal profiles of high-mobility group box 1 expression levels after cortical spreading depression in mice. Cephalalgia. 36(1):44–52. https://doi.org/10.1177/0333102415580100CrossRefPubMed

28.

Ghaemi A, Sajadian A, Khodaie B, Lotfinia AA, Lotfinia M, Aghabarari A, Khaleghi Ghadiri M, Meuth S, Gorji A (2016) Immunomodulatory effect of toll-like Receptor-3 ligand poly I:C on cortical spreading depression. Mol Neurobiol 53(1):143–154. https://doi.org/10.1007/s12035-014-8995-zCrossRefPubMed

29.

Gursoy-Ozdemir Y, Qiu J, Matsuoka N, Bolay H, Bermpohl D, Jin H, Wang X, Rosenberg GA, Lo EH, Moskowitz MA (2004) Cortical spreading depression activates and upregulates MMP-9. J Clin Invest 113(10):1447–1455. https://doi.org/10.1172/JCI200421227CrossRefPubMedPubMedCentral

30.

Hougaard A, Amin FM, Christensen CE, Younis S, Wolfram F, Cramer SP, Larsson HBW, Ashina M (2017) Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura. Brain. 140(6):1633–1642. https://doi.org/10.1093/brain/awx089CrossRefPubMed

31.

Tottene A, Conti R, Fabbro A, Vecchia D, Shapovalova M, Santello M, van den Maagdenberg AMJM, Ferrari MD, Pietrobon D (2009) Enhanced excitatory transmission at cortical synapses as the basis for facilitated spreading depression in ca(v)2.1 knockin migraine mice. Neuron. 61(5):762–773. https://doi.org/10.1016/j.neuron.2009.01.027CrossRefPubMed

32.

van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T et al (2004) A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron. 41(5):701–710. https://doi.org/10.1016/S0896-6273(04)00085-6CrossRefPubMed

33.

Eikermann-Haerter K, Baum MJ, Ferrari MD, van den Maagdenberg AM, Moskowitz MA, Ayata C (2009) Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice. Ann Neurol 66(4):564–568PubMedPubMedCentralCrossRef

34.

Magni G, Boccazzi M, Bodini A, Abbracchio MP, van den Maagdenberg AM, Ceruti S (2019) Basal astrocyte and microglia activation in the central nervous system of familial hemiplegic migraine type I mice. Cephalalgia. 39(14):1809–1817. https://doi.org/10.1177/0333102419861710CrossRefPubMed

35.

Franceschini A, Nair A, Bele T, van den Maagdenberg AM, Nistri A, Fabbretti E (2012) Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine. BMC Neurosci 13:143PubMedPubMedCentralCrossRef

36.

Hullugundi SK, Ferrari MD, van den Maagdenberg AM, Nistri A (2013) The mechanism of functional up-regulation of P2X3 receptors of trigeminal sensory neurons in a genetic mouse model of familial hemiplegic migraine type 1 (FHM-1). PLoS One 8(4):e60677PubMedPubMedCentralCrossRef

37.

Nowodworska A, van den Maagdenberg A, Nistri A, Fabbretti E (2017) In situ imaging reveals properties of purinergic signalling in trigeminal sensory ganglia in vitro. Purinergic Signal 13(4):511–520. https://doi.org/10.1007/s11302-017-9576-1CrossRefPubMedPubMedCentral

38.

Ceruti S, Villa G, Fumagalli M, Colombo L, Magni G, Zanardelli M, Fabbretti E, Verderio C, van den Maagdenberg AMJM, Nistri A, Abbracchio MP (2011) Calcitonin gene-related peptide-mediated enhancement of purinergic neuron/glia communication by the algogenic factor bradykinin in mouse trigeminal ganglia from wild-type and R192Q Cav2.1 Knock-in mice: implications for basic mechanisms of migraine pain. J Neurosci 31(10):3638–3649. https://doi.org/10.1523/JNEUROSCI.6440-10.2011CrossRefPubMedPubMedCentral

39.

Franceschini A, Vilotti S, Ferrari MD, van den Maagdenberg AM, Nistri A, Fabbretti E (2013) TNFalpha levels and macrophages expression reflect an inflammatory potential of trigeminal ganglia in a mouse model of familial hemiplegic migraine. PLoS One 8(1):e52394. https://doi.org/10.1371/journal.pone.0052394CrossRefPubMedPubMedCentral

40.

Albrecht DS, Mainero C, Ichijo E, Ward N, Granziera C, Zurcher NR et al (2019) Imaging of neuroinflammation in migraine with aura: a [(11)C]PBR28 PET/MRI study. Neurology. 92(17):e2038–e2e50PubMedPubMedCentralCrossRef

41.

Loggia ML, Chonde DB, Akeju O, Arabasz G, Catana C, Edwards RR, Hill E, Hsu S, Izquierdo-Garcia D, Ji RR, Riley M, Wasan AD, Zürcher NR, Albrecht DS, Vangel MG, Rosen BR, Napadow V, Hooker JM (2015) Evidence for brain glial activation in chronic pain patients. Brain. 138(Pt 3):604–615. https://doi.org/10.1093/brain/awu377CrossRefPubMedPubMedCentral

42.

Keddie S, Parker T, Lachmann HJ, Ginsberg L (2018) Cryopyrin-associated periodic fever syndrome and the nervous system. Curr Treat Options Neurol 20(10):43PubMedPubMedCentralCrossRef

43.

Cordero MD, Alcocer-Gomez E, Ryffel B (2018) Gain of function mutation and inflammasome driven diseases in human and mouse models. J Autoimmun 91:13–22. https://doi.org/10.1016/j.jaut.2018.03.002CrossRefPubMed

44.

Schuh E, Lohse P, Ertl-Wagner B, Witt M, Krumbholz M, Frankenberger M, Gerdes LA, Hohlfeld R, Kümpfel T (2015) Expanding spectrum of neurologic manifestations in patients with NLRP3 low-penetrance mutations. Neurol Neuroimmunol Neuroinflamm 2(4):e109. https://doi.org/10.1212/NXI.0000000000000109CrossRefPubMedPubMedCentral

45.

Kullenberg T, Lofqvist M, Leinonen M, Goldbach-Mansky R, Olivecrona H (2016) Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes. Rheumatology (Oxford) 55(8):1499–1506CrossRef

46.

Lampron A, Pimentel-Coelho PM, Rivest S (2013) Migration of bone marrow-derived cells into the central nervous system in models of neurodegeneration. J Comp Neurol 521(17):3863–3876. https://doi.org/10.1002/cne.23363CrossRefPubMed

47.

Lamkanfi M, Dixit VM (2014) Mechanisms and functions of inflammasomes. Cell. 157(5):1013–1022. https://doi.org/10.1016/j.cell.2014.04.007CrossRefPubMed

48.

Broz P, Dixit VM (2016) Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol. 16(7):407–420. https://doi.org/10.1038/nri.2016.58CrossRefPubMed

49.

Lamkanfi M, Dixit VM (2012) Inflammasomes and their roles in health and disease. Annu Rev Cell Dev Biol 28(1):137–161. https://doi.org/10.1146/annurev-cellbio-101011-155745CrossRefPubMed

50.

Van Opdenbosch N, Gurung P, Vande Walle L, Fossoul A, Kanneganti TD, Lamkanfi M (2014) Activation of the NLRP1b inflammasome independently of ASC-mediated caspase-1 autoproteolysis and speck formation. Nat Commun 5(1):3209. https://doi.org/10.1038/ncomms4209CrossRefPubMed

51.

Voet S, Srinivasan S, Lamkanfi M, van Loo G (2019) Inflammasomes in neuroinflammatory and neurodegenerative diseases. EMBO Mol Med 11(6):e10248PubMedPubMedCentralCrossRef

52.

Heneka MT, McManus RM, Latz E (2018) Inflammasome signalling in brain function and neurodegenerative disease. Nat Rev Neurosci 19(10):610–621PubMedCrossRef

53.

Yang J, Liu Z, Xiao TS (2017) Post-translational regulation of inflammasomes. Cell Mol Immunol 14(1):65–79. https://doi.org/10.1038/cmi.2016.29CrossRefPubMed

54.

Panicker N, Kam T, Neifert S, Hinkle J, Mao X, Karuppagounder S, Wang H, Kumar M, Pirooznia S, Pletnikova O, Troncoso J, Dawson VL, Dawson TM (2020) NLRP3 inflammasome activation in dopamine neurons contributes to neurodegeneration in Parkinson’s disease. FASEB J 34(S1):1CrossRef

55.

Santoni G, Cardinali C, Morelli MB, Santoni M, Nabissi M, Amantini C (2015) Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons. J Neuroinflammation 12(1):21. https://doi.org/10.1186/s12974-015-0239-2CrossRefPubMedPubMedCentral

56.

Sarchielli P, Alberti A, Baldi A, Coppola F, Rossi C, Pierguidi L, Floridi A, Calabresi P (2006) Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally. Headache. 46(2):200–207. https://doi.org/10.1111/j.1526-4610.2006.00337.xCrossRefPubMed

57.

Oliveira AB, Bachi ALL, Ribeiro RT, Mello MT, Tufik S, Peres MFP (2017) Unbalanced plasma TNF-alpha and IL-12/IL-10 profile in women with migraine is associated with psychological and physiological outcomes. J Neuroimmunol 313:138–144. https://doi.org/10.1016/j.jneuroim.2017.09.008CrossRefPubMed

58.

De Corato A, Lisi L, Capuano A, Tringali G, Tramutola A, Navarra P et al (2011) Trigeminal satellite cells express functional calcitonin gene-related peptide receptors, whose activation enhances interleukin-1beta pro-inflammatory effects. J Neuroimmunol 237(1–2):39–46. https://doi.org/10.1016/j.jneuroim.2011.05.013CrossRefPubMed

59.

Bo SH, Davidsen EM, Gulbrandsen P, Dietrichs E, Bovim G, Stovner LJ et al (2009) Cerebrospinal fluid cytokine levels in migraine, tension-type headache and cervicogenic headache. Cephalalgia. 29(3):365–372. https://doi.org/10.1111/j.1468-2982.2008.01727.xCrossRefPubMed

60.

Chen L, Li X, Huang L, Wu Q, Chen L, Wan Q (2014) Chemical stimulation of the intracranial dura activates NALP3 inflammasome in trigeminal ganglia neurons. Brain Res 1566:1–11. https://doi.org/10.1016/j.brainres.2014.04.019CrossRefPubMed

61.

He W, Long T, Pan Q, Zhang S, Zhang Y, Zhang D, Qin G, Chen L, Zhou J (2019) Microglial NLRP3 inflammasome activation mediates IL-1beta release and contributes to central sensitization in a recurrent nitroglycerin-induced migraine model. J Neuroinflammation 16(1):78. https://doi.org/10.1186/s12974-019-1459-7CrossRefPubMedPubMedCentral

62.

Gross EC, Klement RJ, Schoenen J, D'Agostino DP, Fischer D (2019) Potential Protective Mechanisms of Ketone Bodies in Migraine Prevention. Nutrients 11(4):811PubMedCentralCrossRef

63.

Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D'Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD (2015) The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med 21(3):263–269. https://doi.org/10.1038/nm.3804CrossRefPubMedPubMedCentral

64.

Zhang H, Li F, Li WW, Stary C, Clark JD, Xu S et al (2016) The inflammasome as a target for pain therapy. Br J Anaesth 117(6):693–707PubMedPubMedCentralCrossRef

65.

Matsuoka Y, Yamashita A, Matsuda M, Kawai K, Sawa T, Amaya F (2019) NLRP2 inflammasome in dorsal root ganglion as a novel molecular platform that produces inflammatory pain hypersensitivity. Pain. 160(9):2149–2160. https://doi.org/10.1097/j.pain.0000000000001611CrossRefPubMed

66.

Mulder EJ, Van Baal C, Gaist D, Kallela M, Kaprio J, Svensson DA et al (2003) Genetic and environmental influences on migraine: a twin study across six countries. Twin Res 6(5):422–431PubMedCrossRef

67.

de Vries B, Frants RR, Ferrari MD, van den Maagdenberg AM (2009) Molecular genetics of migraine. Hum Genet 126(1):115–132PubMedCrossRef

68.

Hansen RD, Christensen AF, Olesen J (2017) Family studies to find rare high risk variants in migraine. J Headache Pain. 18(1):32. https://doi.org/10.1186/s10194-017-0729-yCrossRefPubMedPubMedCentral

69.

de Boer I, Terwindt GM, van den Maagdenberg A (2020) Genetics of migraine aura: an update. J Headache Pain. 21(1):64PubMedPubMedCentralCrossRef

70.

Russell MB, Olesen J (1993) The genetics of migraine without aura and migraine with aura. Cephalalgia. 13(4):245–248. https://doi.org/10.1046/j.1468-2982.1993.1304245.xCrossRefPubMed

71.

Russell MB, Olesen J (1995) Increased familial risk and evidence of genetic factor in migraine. BMJ. 311(7004):541–544. https://doi.org/10.1136/bmj.311.7004.541CrossRefPubMedPubMedCentral

72.

Pelzer N, Haan J, Stam AH, Vijfhuizen LS, Koelewijn SC, Smagge A, de Vries B, Ferrari MD, van den Maagdenberg AMJM, Terwindt GM (2018) Clinical spectrum of hemiplegic migraine and chances of finding a pathogenic mutation. Neurology. 90(7):e575–ee82. https://doi.org/10.1212/WNL.0000000000004966CrossRefPubMed

73.

Jander S, Schroeter M, Peters O, Witte OW, Stoll G (2001) Cortical spreading depression induces proinflammatory cytokine gene expression in the rat brain. J Cereb Blood Flow Metab 21(3):218–225PubMedCrossRef

74.

Choudhuri R, Cui L, Yong C, Bowyer S, Klein RM, Welch KM et al (2002) Cortical spreading depression and gene regulation: relevance to migraine. Ann Neurol 51(4):499–506. https://doi.org/10.1002/ana.10158CrossRefPubMed

75.

Eising E, Shyti R, AC’t Hoen P, Vijfhuizen LS, SMH H, LAM B et al (2017) Cortical spreading depression causes unique dysregulation of inflammatory pathways in a transgenic mouse model of migraine. Mol Neurobiol 54(4):2986–2996. https://doi.org/10.1007/s12035-015-9681-5CrossRefPubMed

76.

Lombardo SD, Mazzon E, Basile MS, Cavalli E, Bramanti P, Nania R et al (2019) Upregulation of IL-1 Receptor Antagonist in a Mouse Model of Migraine. Brain Sci 9(7):172PubMedCentralCrossRef

77.

Wang IM, Zhang B, Yang X, Zhu J, Stepaniants S, Zhang C, Meng Q, Peters M, He Y, Ni C, Slipetz D, Crackower MA, Houshyar H, Tan CM, Asante-Appiah E, O'Neill G, Jane Luo M, Thieringer R, Yuan J, Chiu CS, Yee Lum P, Lamb J, Boie Y, Wilkinson HA, Schadt EE, Dai H, Roberts C (2012) Systems analysis of eleven rodent disease models reveals an inflammatome signature and key drivers. Mol Syst Biol 8(1):594. https://doi.org/10.1038/msb.2012.24CrossRefPubMedPubMedCentral

78.

Gormley P, Anttila V, Winsvold BS, Palta P, Esko T, Pers TH et al (2016) Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet 48(8):856–866. https://doi.org/10.1038/ng.3598CrossRefPubMedPubMedCentral

79.

de Monasterio-Schrader P, Patzig J, Mobius W, Barrette B, Wagner TL, Kusch K et al (2013) Uncoupling of neuroinflammation from axonal degeneration in mice lacking the myelin protein tetraspanin-2. Glia. 61(11):1832–1847. https://doi.org/10.1002/glia.22561CrossRefPubMed

80.

Yang S, Gao L, Lu F, Wang B, Gao F, Zhu G, Cai Z, Lai J, Yang Q (2015) Transcription factor myocyte enhancer factor 2D regulates interleukin-10 production in microglia to protect neuronal cells from inflammation-induced death. J Neuroinflammation 12(1):33. https://doi.org/10.1186/s12974-015-0258-zCrossRefPubMedPubMedCentral

81.

Lu B, Wang H, Andersson U, Tracey KJ (2013) Regulation of HMGB1 release by inflammasomes. Protein Cell 4(3):163–167PubMedPubMedCentralCrossRef

82.

Weber C, Fraemohs L, Dejana E (2007) The role of junctional adhesion molecules in vascular inflammation. Nat Rev Immunol 7(6):467–477. https://doi.org/10.1038/nri2096CrossRefPubMed

83.

Zheng R, Liu H, Zhou Y, Yan D, Chen J, Ma D et al (2018) Notch4 negatively regulates the inflammatory response to mycobacterium tuberculosis infection by inhibiting TAK1 activation. J Infect Dis 218(2):312–323PubMedCrossRef

84.

Zhao H, Eising E, de Vries B, Vijfhuizen LS (2016) International headache genetics C, Anttila V, et al. gene-based pleiotropy across migraine with aura and migraine without aura patient groups. Cephalalgia. 36(7):648–657. https://doi.org/10.1177/0333102415591497CrossRefPubMed

85.

Elson JL, Majamaa K, Howell N, Chinnery PF (2007) Associating mitochondrial DNA variation with complex traits. Am J Hum Genet 80(2):378–382; author reply 82-3. https://doi.org/10.1086/511652CrossRefPubMedPubMedCentral

86.

Yorns WR Jr, Hardison HH (2013) Mitochondrial dysfunction in migraine. Semin Pediatr Neurol 20(3):188–193PubMedCrossRef

87.

Lemos C, Alonso I, Barros J, Sequeiros J, Pereira-Monteiro J, Mendonca D et al (2012) Assessing risk factors for migraine: differences in gender transmission. PLoS One 7(11):e50626. https://doi.org/10.1371/journal.pone.0050626CrossRefPubMedPubMedCentral

88.

Rosen N (2008) Headache and mitochondrial disorders. Headache. 48(5):733–734. https://doi.org/10.1111/j.1526-4610.2008.01118.xCrossRefPubMed

89.

Uncini A, Lodi R, Di Muzio A, Silvestri G, Servidei S, Lugaresi A et al (1995) Abnormal brain and muscle energy metabolism shown by 31P-MRS in familial hemiplegic migraine. J Neurol Sci 129(2):214–222. https://doi.org/10.1016/0022-510X(94)00283-TCrossRefPubMed

90.

Sparaco M, Feleppa M, Lipton RB, Rapoport AM, Bigal ME (2006) Mitochondrial dysfunction and migraine: evidence and hypotheses. Cephalalgia. 26(4):361–372. https://doi.org/10.1111/j.1468-2982.2005.01059.xCrossRefPubMed

91.

Zaki EA, Freilinger T, Klopstock T, Baldwin EE, Heisner KR, Adams K, Dichgans M, Wagler S, Boles RG (2009) Two common mitochondrial DNA polymorphisms are highly associated with migraine headache and cyclic vomiting syndrome. Cephalalgia. 29(7):719–728. https://doi.org/10.1111/j.1468-2982.2008.01793.xCrossRefPubMed

92.

Woodbridge P, Liang C, Davis RL, Vandebona H, Sue CM (2013) POLG mutations in Australian patients with mitochondrial disease. Intern Med J 43(2):150–156. https://doi.org/10.1111/j.1445-5994.2012.02847.xCrossRefPubMed

93.

Borte S, Zwart JA, Skogholt AH, Gabrielsen ME, Thomas LF, Fritsche LG et al (2020) Mitochondrial genome-wide association study of migraine - the HUNT study. Cephalalgia. 40(6):625–634. https://doi.org/10.1177/0333102420906835CrossRefPubMedPubMedCentral

94.

Vollono C, Primiano G, Della Marca G, Losurdo A, Servidei S (2018) Migraine in mitochondrial disorders: prevalence and characteristics. Cephalalgia. 38(6):1093–1106PubMedCrossRef

95.

Smeitink J, Koene S, Beyrath J, Saris C, Turnbull D, Janssen M (2019) Mitochondrial migraine: disentangling the angiopathy paradigm in m.3243A>G patients. JIMD Rep 46(1):52–62PubMedPubMedCentral

96.

Kim HK, Chen W, Andreazza AC (2015) The potential role of the NLRP3 Inflammasome as a link between mitochondrial complex I dysfunction and inflammation in bipolar disorder. Neural Plast 2015:408136PubMedPubMedCentralCrossRef

97.

Wei P, Yang F, Zheng Q, Tang W, Li J (2019) The potential role of the NLRP3 Inflammasome activation as a link between mitochondria ROS generation and Neuroinflammation in postoperative cognitive dysfunction. Front Cell Neurosci 13:73. https://doi.org/10.3389/fncel.2019.00073CrossRefPubMedPubMedCentral

98.

Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature. 469(7329):221–225. https://doi.org/10.1038/nature09663CrossRefPubMed

99.

Alfonso-Loeches S, Urena-Peralta JR, Morillo-Bargues MJ, Oliver-De La Cruz J, Guerri C (2014) Role of mitochondria ROS generation in ethanol-induced NLRP3 inflammasome activation and cell death in astroglial cells. Front Cell Neurosci 8:216PubMedPubMedCentralCrossRef

100.

Zhong Z, Zhai Y, Liang S, Mori Y, Han R, Sutterwala FS, Qiao L (2013) TRPM2 links oxidative stress to NLRP3 inflammasome activation. Nat Commun 4(1):1611. https://doi.org/10.1038/ncomms2608CrossRefPubMed

101.

Horng T (2014) Calcium signaling and mitochondrial destabilization in the triggering of the NLRP3 inflammasome. Trends Immunol 35(6):253–261. https://doi.org/10.1016/j.it.2014.02.007CrossRefPubMedPubMedCentral

102.

Lu B, Kwan K, Levine YA, Olofsson PS, Yang H, Li J, Joshi S, Wang H, Andersson U, Chavan SS, Tracey KJ (2014) alpha7 nicotinic acetylcholine receptor signaling inhibits inflammasome activation by preventing mitochondrial DNA release. Mol Med 20(1):350–358. https://doi.org/10.2119/molmed.2013.00117CrossRefPubMedPubMedCentral

103.

Morais A, Liu TT, Qin T, Sadhegian H, Ay I, Yagmur D et al (2020) Vagus nerve stimulation inhibits cortical spreading depression exclusively through central mechanisms. Pain. 161(7):1661–1669PubMedCrossRefPubMedCentral

104.

Cornelison LE, Woodman SE, Durham PL (2020) Inhibition of trigeminal nociception by non-invasive Vagus nerve stimulation: investigating the role of GABAergic and serotonergic pathways in a model of episodic migraine. Front Neurol 11:146PubMedPubMedCentralCrossRef

105.

Hawkins JL, Cornelison LE, Blankenship BA, Durham PL (2017) Vagus nerve stimulation inhibits trigeminal nociception in a rodent model of episodic migraine. Pain Rep 2(6):e628. https://doi.org/10.1097/PR9.0000000000000628CrossRefPubMedPubMedCentral

106.

Scher AI, Bigal ME, Lipton RB (2005) Comorbidity of migraine. Curr Opin Neurol 18(3):305–310. https://doi.org/10.1097/01.wco.0000169750.52406.a2CrossRefPubMed

107.

Buse DC, Reed ML, Fanning KM, Bostic R, Dodick DW, Schwedt TJ, Munjal S, Singh P, Lipton RB (2020) Comorbid and co-occurring conditions in migraine and associated risk of increasing headache pain intensity and headache frequency: results of the migraine in America symptoms and treatment (MAST) study. J Headache Pain 21(1):23. https://doi.org/10.1186/s10194-020-1084-yCrossRefPubMedPubMedCentral

108.

Sutherland HG, Griffiths LR (2017) Genetics of migraine: insights into the molecular basis of migraine disorders. Headache. 57(4):537–569PubMedCrossRef

109.

Brainstorm C, Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J et al (2018) Analysis of shared heritability in common disorders of the brain. Science 360(6395):eaap8757CrossRef

110.

Lee MJ, Lee C, Chung CS (2016) The migraine-stroke connection. J Stroke 18(2):146–156. https://doi.org/10.5853/jos.2015.01683CrossRefPubMedPubMedCentral

111.

Yemisci M, Eikermann-Haerter K (2019) Aura and Stroke: relationship and what we have learnt from preclinical models. J Headache Pain. 20(1):63PubMedPubMedCentralCrossRef

112.

Kim H, Seo JS, Lee SY, Ha KT, Choi BT, Shin YI et al (2020) AIM2 inflammasome contributes to brain injury and chronic post-stroke cognitive impairment in mice. Brain Behav Immun 87:765–776PubMedCrossRef

113.

Poh L, Kang SW, Baik SH, Ng GYQ, She DT, Balaganapathy P, Dheen ST, Magnus T, Gelderblom M, Sobey CG, Koo EH, Fann DY, Arumugam TV (2019) Evidence that NLRC4 inflammasome mediates apoptotic and pyroptotic microglial death following ischemic stroke. Brain Behav Immun 75:34–47. https://doi.org/10.1016/j.bbi.2018.09.001CrossRefPubMed

114.

Yang F, Wang Z, Wei X, Han H, Meng X, Zhang Y, Shi W, Li F, Xin T, Pang Q, Yi F (2014) NLRP3 deficiency ameliorates neurovascular damage in experimental ischemic stroke. J Cereb Blood Flow Metab 34(4):660–667. https://doi.org/10.1038/jcbfm.2013.242CrossRefPubMedPubMedCentral

115.

Fann DY, Lee SY, Manzanero S, Tang SC, Gelderblom M, Chunduri P et al (2013) Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke. Cell Death Dis 4:e790PubMedCrossRef

116.

Cao Y, Zhang H, Lu X, Wang J, Zhang X, Sun S, Bao Z, Tian W, Ning S, Wang L, Cui L (2020) Overexpression of MicroRNA-9a-5p ameliorates NLRP1 Inflammasome-mediated ischemic injury in rats following ischemic stroke. Neuroscience. 444:106–117. https://doi.org/10.1016/j.neuroscience.2020.01.008CrossRefPubMed

117.

Franke M, Bieber M, Kraft P, Weber ANR, Stoll G, Schuhmann MK (2021) The NLRP3 inflammasome drives inflammation in ischemia/reperfusion injury after transient middle cerebral artery occlusion in mice. Brain Behav Immun 92:223–233PubMedCrossRef

118.

Liao KC, Mogridge J (2013) Activation of the Nlrp1b inflammasome by reduction of cytosolic ATP. Infect Immun 81(2):570–579. https://doi.org/10.1128/IAI.01003-12CrossRefPubMedPubMedCentral

119.

Nomura J, So A, Tamura M, Busso N (2015) Intracellular ATP decrease mediates NLRP3 Inflammasome activation upon Nigericin and crystal stimulation. J Immunol 195(12):5718–5724PubMedCrossRef

120.

Munoz-Planillo R, Kuffa P, Martinez-Colon G, Smith BL, Rajendiran TM, Nunez G (2013) K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity. 38(6):1142–1153PubMedPubMedCentralCrossRef

121.

Rajamaki K, Nordstrom T, Nurmi K, Akerman KE, Kovanen PT, Oorni K et al (2013) Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3 inflammasome. J Biol Chem 288(19):13410–13419PubMedPubMedCentralCrossRef

122.

Denes A, Pinteaux E, Rothwell NJ, Allan SM (2011) Interleukin-1 and stroke: biomarker, harbinger of damage, and therapeutic target. Cerebrovasc Dis 32(6):517–527. https://doi.org/10.1159/000332205CrossRefPubMed

123.

Zhu Z, Yan J, Geng C, Wang D, Li C, Feng S et al (2016) A polymorphism within the 3'UTR of NLRP3 is associated with susceptibility for ischemic stroke in Chinese population. Cell Mol Neurobiol 36(6):981–988PubMedCrossRef

124.

Mantegazza M, Cestele S (2018) Pathophysiological mechanisms of migraine and epilepsy: similarities and differences. Neurosci Lett 667:92–102. https://doi.org/10.1016/j.neulet.2017.11.025CrossRefPubMed

125.

Kossoff EH, Andermann F (2010) Migraine and epilepsy. Semin Pediatr Neurol 17(2):117–122. https://doi.org/10.1016/j.spen.2010.04.005CrossRefPubMed

126.

Vezzani A, French J, Bartfai T, Baram TZ (2011) The role of inflammation in epilepsy. Nat Rev Neurol 7(1):31–40PubMedCrossRef

127.

Tan CC, Zhang JG, Tan MS, Chen H, Meng DW, Jiang T, Meng XF, Li Y, Sun Z, Li MM, Yu JT, Tan L (2015) NLRP1 inflammasome is activated in patients with medial temporal lobe epilepsy and contributes to neuronal pyroptosis in amygdala kindling-induced rat model. J Neuroinflammation 12(1):18. https://doi.org/10.1186/s12974-014-0233-0CrossRefPubMedPubMedCentral

128.

Meng XF, Tan L, Tan MS, Jiang T, Tan CC, Li MM, Wang HF, Yu JT (2014) Inhibition of the NLRP3 inflammasome provides neuroprotection in rats following amygdala kindling-induced status epilepticus. J Neuroinflammation 11(1):212. https://doi.org/10.1186/s12974-014-0212-5CrossRefPubMedPubMedCentral

129.

Shen K, Mao Q, Yin X, Zhang C, Jin Y, Deng A et al (2018) NLRP3 Inflammasome activation leads to epileptic neuronal apoptosis. Curr Neurovasc Res 15(4):276–281PubMedCrossRef

130.

Yue J, Wei YJ, Yang XL, Liu SY, Yang H, Zhang CQ (2020) NLRP3 inflammasome and endoplasmic reticulum stress in the epileptogenic zone in temporal lobe epilepsy: molecular insights into their interdependence. Neuropathol Appl Neurobiol 46(7):770–785. https://doi.org/10.1111/nan.12621CrossRefPubMed

131.

Bolay H, Ozge A, Uluduz D, Baykan B (2020) Are migraine patients at increased risk for symptomatic coronavirus disease 2019 due to shared comorbidities? Headache. 60(10):2508–2521. https://doi.org/10.1111/head.13998CrossRefPubMed

132.

Lenart N, Brough D, Denes A (2016) Inflammasomes link vascular disease with neuroinflammation and brain disorders. J Cereb Blood Flow Metab 36(10):1668–1685. https://doi.org/10.1177/0271678X16662043CrossRefPubMedPubMedCentral

133.

Guo H, Callaway JB, Ting JP (2015) Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med 21(7):677–687PubMedPubMedCentralCrossRef

134.

Nieto-Torres JL, Verdia-Baguena C, Jimenez-Guardeno JM, Regla-Nava JA, Castano-Rodriguez C, Fernandez-Delgado R et al (2015) Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome. Virology. 485:330–339. https://doi.org/10.1016/j.virol.2015.08.010CrossRefPubMed

135.

Shah A (2020) Novel coronavirus-induced NLRP3 Inflammasome activation: a potential drug target in the treatment of COVID-19. Front Immunol 11:1021. https://doi.org/10.3389/fimmu.2020.01021CrossRefPubMedPubMedCentral

136.

Rodrigues TS, de Sa KSG, Ishimoto AY, Becerra A, Oliveira S, Almeida L et al (2021) Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J Exp Med 218(3):e20201707PubMedCrossRef

137.

Ribeiro DE, Oliveira-Giacomelli A, Glaser T, Arnaud-Sampaio VF, Andrejew R, Dieckmann L et al (2021) Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology. Mol Psychiatry 26(4):1044–1059PubMedCrossRef

138.

Bolay H, Gul A, Baykan B (2020) COVID-19 is a real headache! Headache. 60(7):1415–1421PubMedCrossRef

Title: Migraine and neuroinflammation: the inflammasome perspective
Authors: Oguzhan Kursun
Muge Yemisci
Arn M. J. M. van den Maagdenberg
Hulya Karatas
Publication date: 01-12-2021
Publisher: Springer Milan
Keyword: Migraine
Published in: The Journal of Headache and Pain / Issue 1/2021
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-021-01271-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Migraine and neuroinflammation: the inflammasome perspective

Abstract

Background

Main body

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Main body

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

Selective denervation of the corrugator supercilii muscle for the treatment of idiopatic trigeminal neuralgia purely paroxysmal distributed in the supraorbital and suprathrochlear dermatomes

Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy

Long term safety, tolerability, and efficacy of intracutaneous zolmitriptan (M207) in the acute treatment of migraine

Effect of galcanezumab on severity and symptoms of migraine in phase 3 trials in patients with episodic or chronic migraine

Advantages of imaging photoplethysmography for migraine modeling: new optical markers of trigemino‐vascular activation in rats

Src family kinases activity is required for transmitting purinergic P2X7 receptor signaling in cortical spreading depression and neuroinflammation