1932

Abstract

Migraine is a complex neurovascular pain disorder linked to the meninges, a border tissue innervated by neuropeptide-containing primary afferent fibers chiefly from the trigeminal nerve. Electrical or mechanical stimulation of this nerve surrounding large blood vessels evokes headache patterns as in migraine, and the brain, blood, and meninges are likely sources of headache triggers. Cerebrospinal fluid may play a significant role in migraine by transferring signals released from the brain to overlying pain-sensitive meningeal tissues, including dura mater. Interactions between trigeminal afferents, neuropeptides, and adjacent meningeal cells and tissues cause neurogenic inflammation, a critical target for current prophylactic and abortive migraine therapies. Here we review the importance of the cranial meninges to migraine headaches, explore the properties of trigeminal meningeal afferents, and briefly review emerging concepts, such as meningeal neuroimmune interactions, that may one day prove therapeutically relevant.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-neuro-080422-105509
2023-07-10
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/neuro/46/1/annurev-neuro-080422-105509.html?itemId=/content/journals/10.1146/annurev-neuro-080422-105509&mimeType=html&fmt=ahah

Literature Cited

  1. Afridi SK, Matharu MS, Lee L, Kaube H, Friston KJ et al. 2005. A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate. Brain 128:932–39
    [Google Scholar]
  2. Akerman S, Karsan N, Bose P, Hoffmann JR, Holland PR et al. 2019. Nitroglycerine triggers triptan-responsive cranial allodynia and trigeminal neuronal hypersensitivity. Brain 142:103–19
    [Google Scholar]
  3. Al-Karagholi MA, Hansen JM, Guo S, Olesen J, Ashina M. 2019. Opening of ATP-sensitive potassium channels causes migraine attacks: a new target for the treatment of migraine. Brain 142:2644–54
    [Google Scholar]
  4. Alves De Lima K, Rustenhoven J, Kipnis J. 2020. Meningeal immunity and its function in maintenance of the central nervous system in health and disease. Annu. Rev. Immunol. 38:597–620
    [Google Scholar]
  5. Ampie L, McGavern DB. 2022. Immunological defense of CNS barriers against infections. Immunity 55:781–99
    [Google Scholar]
  6. Andres KH, von During M, Muszynski K, Schmidt RF. 1987. Nerve fibres and their terminals of the dura mater encephali of the rat. Anat. Embryol. 175:289–301
    [Google Scholar]
  7. Ashina M, Dolezil D, Bonner JH, Zhou L, Klatt J et al. 2021. A phase 2, randomized, double-blind, placebo-controlled trial of AMG 301, a pituitary adenylate cyclase-activating polypeptide PAC1 receptor monoclonal antibody for migraine prevention. Cephalalgia 41:33–44
    [Google Scholar]
  8. Ashina M, Møller Hansen J, Oladóttir Á, Dunga B, Olesen J 2017. Human models of migraine—short-term pain for long-term gain. Nat. Rev. Neurol. 13:713–24
    [Google Scholar]
  9. Ashina M, Vasudeva R, Jin L, Lombard L, Gray E et al. 2019. Onset of efficacy following oral treatment with lasmiditan for the acute treatment of migraine: integrated results from 2 randomized double-blind placebo-controlled phase 3 clinical studies. Headache 59:1788–801
    [Google Scholar]
  10. Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S et al. 2015. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J. Exp. Med. 212:991–99
    [Google Scholar]
  11. Avona A, Burgos-Vega C, Burton MD, Akopian AN, Price TJ, Dussor G. 2019. Dural calcitonin gene-related peptide produces female-specific responses in rodent migraine models. J. Neurosci. 39:4323–31
    [Google Scholar]
  12. Avona A, Mason BN, Burgos-Vega C, Hovhannisyan AH, Belugin SN et al. 2021. Meningeal CGRP-prolactin interaction evokes female-specific migraine behavior. Ann. Neurol. 89:1129–44
    [Google Scholar]
  13. Ayata C, Jin H, Kudo C, Dalkara T, Moskowitz MA. 2006. Suppression of cortical spreading depression in migraine prophylaxis. Ann. Neurol. 59:652–61
    [Google Scholar]
  14. Azimi E, Reddy VB, Pereira PJS, Talbot S, Woolf CJ, Lerner EA. 2017. Substance P activates Mas-related G protein-coupled receptors to induce itch. J. Allergy Clin. Immunol. 140:447–53.e3
    [Google Scholar]
  15. Bigal ME, Ashina S, Burstein R, Reed ML, Buse D et al. 2008. Prevalence and characteristics of allodynia in headache sufferers: a population study. Neurology 70:1525–33
    [Google Scholar]
  16. Binshtok AM, Wang H, Zimmermann K, Amaya F, Vardeh D et al. 2008. Nociceptors are interleukin-1β sensors. J. Neurosci. 28:14062–73
    [Google Scholar]
  17. Blaeser AS, Sugden A, Zhao J, Carneiro-Nascimento S, Shipley FB et al. 2022. Trigeminal afferents sense locomotion-related meningeal deformations. Cell Rep. 41:111648
    [Google Scholar]
  18. Blau JN, Dexter SL. 1981. The site of pain origin during migraine attacks. Cephalalgia 1:143–47
    [Google Scholar]
  19. 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. 8:136–42
    [Google Scholar]
  20. Bouchelet I, Cohen Z, Case B, Seguela P, Hamel E 1996. Differential expression of sumatriptan-sensitive 5-hydroxytryptamine receptors in human trigeminal ganglia and cerebral blood vessels. Mol. Pharmacol. 50:219–23
    [Google Scholar]
  21. Bove GM, Moskowitz MA. 1997. Primary afferent neurons innervating guinea pig dura. J. Neurophysiol. 77:299–308
    [Google Scholar]
  22. Burgos-Vega CC, Quigley LD, Avona A, Price T, Dussor G. 2016. Dural stimulation in rats causes brain-derived neurotrophic factor-dependent priming to subthreshold stimuli including a migraine trigger. Pain 157:2722–30
    [Google Scholar]
  23. Burstein R, Yamamura H, Malick A, Strassman AM. 1998. Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J. Neurophysiol. 79:964–82
    [Google Scholar]
  24. Buzzi MG, Carter WB, Shimizu T, Heath H 3rd, Moskowitz MA 1991. Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion. Neuropharmacology 30:1193–200
    [Google Scholar]
  25. Buzzi MG, Moskowitz MA. 1990. The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater. Br. J. Pharmacol. 99:202–6
    [Google Scholar]
  26. Cai R, Pan C, Ghasemigharagoz A, Todorov MI, Forstera B et al. 2019. Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull-meninges connections. Nat. Neurosci. 22:317–27
    [Google Scholar]
  27. Carneiro-Nascimento S, Levy D 2022. Cortical spreading depression and meningeal nociception. Neurobiol. Pain 11:100091
    [Google Scholar]
  28. Chizh B, Palmer J, Lai R, Guillard F, Bullman J et al. 2009. A randomised, two-period cross-over study to investigate the efficacy of the Trpv1 antagonist SB-705498 in acute migraine. Eur. J. Pain 13:S202a
    [Google Scholar]
  29. Chu C, Artis D, Chiu IM. 2020. Neuro-immune interactions in the tissues. Immunity 52:464–74
    [Google Scholar]
  30. Coles JA, Myburgh E, Brewer JM, McMenamin PG. 2017. Where are we? The anatomy of the murine cortical meninges revisited for intravital imaging, immunology, and clearance of waste from the brain. Prog. Neurobiol. 156:107–48
    [Google Scholar]
  31. Connor KM, Shapiro RE, Diener HC, Lucas S, Kost J et al. 2009. Randomized, controlled trial of telcagepant for the acute treatment of migraine. Neurology 73:970–77
    [Google Scholar]
  32. Cowan RP, Gross NB, Sweeney MD, Sagare AP, Montagne A et al. 2021. Evidence that blood-CSF barrier transport, but not inflammatory biomarkers, change in migraine, while CSF sVCAM1 associates with migraine frequency and CSF fibrinogen. Headache 61:536–45
    [Google Scholar]
  33. Csiba L, Paschen W, Mies G. 1985. Regional changes in tissue pH and glucose content during cortical spreading depression in rat brain. Brain Res. 336:167–70
    [Google Scholar]
  34. De Logu F, Nassini R, Hegron A, Landini L, Jensen DD et al. 2022. Schwann cell endosome CGRP signals elicit periorbital mechanical allodynia in mice. Nat. Commun. 13:646
    [Google Scholar]
  35. Dodick DW, Goadsby PJ, Silberstein SD, Lipton RB, Olesen J et al. 2014. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. 13:1100–7
    [Google Scholar]
  36. Dreier JP. 2011. The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat. Med. 17:439–47
    [Google Scholar]
  37. Dux M, Santha P, Jancso G. 2003. Capsaicin-sensitive neurogenic sensory vasodilatation in the dura mater of the rat. J. Physiol. 552:859–67
    [Google Scholar]
  38. Dux M, Will C, Vogler B, Filipovic MR, Messlinger K. 2016. Meningeal blood flow is controlled by H2S-NO crosstalk activating a HNO-TRPA1-CGRP signalling pathway. Br. J. Pharmacol. 173:431–45
    [Google Scholar]
  39. Edelmayer RM, Le LN, Yan J, Wei X, Nassini R et al. 2012. Activation of TRPA1 on dural afferents: a potential mechanism of headache pain. Pain 153:1949–58
    [Google Scholar]
  40. Edelmayer RM, Vanderah TW, Majuta L, Zhang ET, Fioravanti B et al. 2009. Medullary pain facilitating neurons mediate allodynia in headache-related pain. Ann. Neurol. 65:184–93
    [Google Scholar]
  41. Enger R, Tang W, Vindedal GF, Jensen V, Helm PJ et al. 2015. Dynamics of ionic shifts in cortical spreading depression. Cereb. Cortex 25:4469–76
    [Google Scholar]
  42. Ferrari MD, Goadsby PJ, Burstein R, Kurth T, Ayata C et al. 2022. Migraine. Nat. Rev. Dis. Primers 8:2
    [Google Scholar]
  43. Fontaine D, Almairac F, Santucci S, Fernandez C, Dallel R et al. 2018. Dural and pial pain-sensitive structures in humans: new inputs from awake craniotomies. Brain 141:1040–48
    [Google Scholar]
  44. Fricke B, von Düring M, Andres KH. 1997. Topography and immunocytochemical characterization of nerve fibers in the leptomeningeal compartments of the rat. A light- and electron-microscopical study. Cell Tissue Res. 287:11–22
    [Google Scholar]
  45. Gao X, Zhang D, Xu C, Li H, Caron KM, Frenette PS. 2021. Nociceptive nerves regulate haematopoietic stem cell mobilization. Nature 589:591–96
    [Google Scholar]
  46. Gao YR, Drew PJ. 2016. Effects of voluntary locomotion and calcitonin gene-related peptide on the dynamics of single dural vessels in awake mice. J. Neurosci. 36:2503–16
    [Google Scholar]
  47. Gariepy H, Zhao J, Levy D. 2017. Differential contribution of COX-1 and COX-2 derived prostanoids to cortical spreading depression—evoked cerebral oligemia. J. Cereb. Blood Flow. Metab. 37:1060–68
    [Google Scholar]
  48. GBD 2019 Dis. Inj. Collab. 2020. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 396:1204–22
    [Google Scholar]
  49. Ghanizada H, Al-Karagholi MA, Walker CS, Arngrim N, Rees T et al. 2021. Amylin analog pramlintide induces migraine-like attacks in patients. Ann. Neurol. 89:1157–71
    [Google Scholar]
  50. Green DP, Limjunyawong N, Gour N, Pundir P, Dong X. 2019. A mast-cell-specific receptor mediates neurogenic inflammation and pain. Neuron 101:412–20.e3
    [Google Scholar]
  51. Guo Z, Qiu CS, Jiang X, Zhang J, Li F et al. 2019. TRESK K+ channel activity regulates trigeminal nociception and headache. eNeuro 6:ENEURO.0236–19.2019
    [Google Scholar]
  52. Hadjikhani N, Albrecht DS, Mainero C, Ichijo E, Ward N et al. 2020. Extra-axial inflammatory signal in parameninges in migraine with visual aura. Ann. Neurol. 87:939–49
    [Google Scholar]
  53. Hadjikhani N, Sanchez del Rio M, Wu O, Schwartz D, Bakker D et al. 2001. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. PNAS 98:4687–92
    [Google Scholar]
  54. Hansen JM, Hauge AW, Olesen J, Ashina M. 2010. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia 30:1179–86
    [Google Scholar]
  55. Hansted AK, Jensen LJ, Olesen J, Jansen-Olesen I. 2020. Localization of TRPA1 channels and characterization of TRPA1 mediated responses in dural and pial arteries in vivo after intracarotid infusion of Na2S. Cephalalgia 40:1310–20
    [Google Scholar]
  56. Harriott AM, Gold MS. 2009. Electrophysiological properties of dural afferents in the absence and presence of inflammatory mediators. J. Neurophysiol. 101:3126–34
    [Google Scholar]
  57. Hassler SN, Ahmad FB, Burgos-Vega CC, Boitano S, Vagner J et al. 2019. Protease activated receptor 2 (PAR2) activation causes migraine-like pain behaviors in mice. Cephalalgia 39:111–22
    [Google Scholar]
  58. Herisson F, Frodermann V, Courties G, Rohde D, Sun Y et al. 2018. Direct vascular channels connect skull bone marrow and the brain surface enabling myeloid cell migration. Nat. Neurosci. 21:1209–17
    [Google Scholar]
  59. Jensen DD, Lieu T, Halls ML, Veldhuis NA, Imlach WL et al. 2017. Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief. Sci. Transl. Med. 9:eaal3447
    [Google Scholar]
  60. Karatas H, Erdener SE, Gursoy-Ozdemir Y, Lule S, Eren-Kocak E et al. 2013. Spreading depression triggers headache by activating neuronal Panx1 channels. Science 339:1092–95
    [Google Scholar]
  61. Karsan N, Bose PR, Thompson C, Newman J, Goadsby PJ. 2020. Headache and non-headache symptoms provoked by nitroglycerin in migraineurs: a human pharmacological triggering study. Cephalalgia 40:828–41
    [Google Scholar]
  62. Kosaras B, Jakubowski M, Kainz V, Burstein R. 2009. Sensory innervation of the calvarial bones of the mouse. J. Comp. Neurol. 515:331–48
    [Google Scholar]
  63. Labastida-Ramirez A, Rubio-Beltran E, Haanes KA, Chan KY, Garrelds IM et al. 2020. Lasmiditan inhibits calcitonin gene-related peptide release in the rodent trigeminovascular system. Pain 161:1092–99
    [Google Scholar]
  64. Lafreniere RG, Cader MZ, Poulin JF, Andres-Enguix I, Simoneau M et al. 2010. A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura. Nat. Med. 16:1157–60
    [Google Scholar]
  65. Lambert GA, Davis JB, Appleby JM, Chizh BA, Hoskin KL, Zagami AS. 2009. The effects of the TRPV1 receptor antagonist SB-705498 on trigeminovascular sensitisation and neurotransmission. Naunyn-Schmiedeberg's Arch. Pharmacol. 380:311–25
    [Google Scholar]
  66. Lashley KS. 1941. Patterns of cerebral integration indicated by the scotoma of migraine. Arch. Neurol. Psychiatry 46:331–39
    [Google Scholar]
  67. Lauritzen M, Hansen AJ, Kronborg D, Wieloch T. 1990. Cortical spreading depression is associated with arachidonic acid accumulation and preservation of energy charge. J. Cereb. Blood Flow Metab. 10:115–22
    [Google Scholar]
  68. Lee WS, Moussaoui SM, Moskowitz MA. 1994. Blockade by oral or parenteral RPR 100893 (a non-peptide NK1 receptor antagonist) of neurogenic plasma protein extravasation within guinea-pig dura mater and conjunctiva. Br. J. Pharmacol. 112:920–24
    [Google Scholar]
  69. Lennerz JK, Ruhle V, Ceppa EP, Neuhuber WL, Bunnett NW et al. 2008. Calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and calcitonin gene-related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: differences between peripheral and central CGRP receptor distribution. J. Comp. Neurol. 507:1277–99
    [Google Scholar]
  70. Levy D, Burstein R, Kainz V, Jakubowski M, Strassman AM. 2007. Mast cell degranulation activates a pain pathway underlying migraine headache. Pain 130:166–76
    [Google Scholar]
  71. Levy D, Burstein R, Strassman AM. 2005. Calcitonin gene-related peptide does not excite or sensitize meningeal nociceptors: implications for the pathophysiology of migraine. Ann. Neurol. 58:698–705
    [Google Scholar]
  72. Levy D, Jakubowski M, Burstein R. 2004. Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT1B/1D receptor agonists. PNAS 101:4274–79
    [Google Scholar]
  73. Levy D, Kainz V, Burstein R, Strassman AM. 2012. Mast cell degranulation distinctly activates trigemino-cervical and lumbosacral pain pathways and elicits widespread tactile pain hypersensitivity. Brain Behav. Immun. 26:311–17
    [Google Scholar]
  74. Levy D, Strassman AM. 2002a. Distinct sensitizing effects of the cAMP-PKA second messenger cascade on rat dural mechanonociceptors. J. Physiol. 538:483–93
    [Google Scholar]
  75. Levy D, Strassman AM. 2002b. Mechanical response properties of A and C primary afferent neurons innervating the rat intracranial dura. J. Neurophysiol. 88:3021–31
    [Google Scholar]
  76. Levy D, Strassman AM. 2004. Modulation of dural nociceptor mechanosensitivity by the nitric oxide-cyclic GMP signaling cascade. J. Neurophysiol. 92:766–72
    [Google Scholar]
  77. Liu-Chen LY, Mayberg MR, Moskowitz MA. 1983. Immunohistochemical evidence for a substance P-containing trigeminovascular pathway to pial arteries in cats. Brain Res. 268:162–66
    [Google Scholar]
  78. Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ et al. 2018. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat. Neurosci. 21:1380–91
    [Google Scholar]
  79. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ et al. 2015. Structural and functional features of central nervous system lymphatic vessels. Nature 523:337–41
    [Google Scholar]
  80. Markowitz S, Saito K, Moskowitz MA. 1987. Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain. J. Neurosci. 7:4129–36
    [Google Scholar]
  81. May A, Goadsby PJ. 2001. Substance P receptor antagonists in the therapy of migraine. Expert Opin. Investig. Drugs 10:673–78
    [Google Scholar]
  82. Mayberg M, Langer RS, Zervas NT, Moskowitz MA. 1981. Perivascular meningeal projections from cat trigeminal ganglia: possible pathway for vascular headaches in man. Science 213:228–30
    [Google Scholar]
  83. Mayberg M, Zervas NT, Moskowitz MA. 1984. Trigeminal projections to supratentorial pial and dural blood vessels in cats demonstrated by horseradish peroxidase histochemistry. J. Comp. Neurol. 223:46–56
    [Google Scholar]
  84. Mazzitelli JA, Smyth LCD, Cross KA, Dykstra T, Sun J et al. 2022. Cerebrospinal fluid regulates skull bone marrow niches via direct access through dural channels. Nat. Neurosci. 25:555–60
    [Google Scholar]
  85. Meents JE, Hoffmann J, Chaplan SR, Neeb L, Schuh-Hofer S et al. 2015. Two TRPV1 receptor antagonists are effective in two different experimental models of migraine. J. Headache Pain 16:57
    [Google Scholar]
  86. Melo-Carrillo A, Strassman AM, Nir RR, Schain AJ, Noseda R et al. 2017. Fremanezumab—a humanized monoclonal anti-CGRP antibody—inhibits thinly myelinated (Aδ) but not unmyelinated (C) meningeal nociceptors. J. Neurosci. 37:10587–96
    [Google Scholar]
  87. Miller S, Liu H, Warfvinge K, Shi L, Dovlatyan M et al. 2016. Immunohistochemical localization of the calcitonin gene-related peptide binding site in the primate trigeminovascular system using functional antagonist antibodies. Neuroscience 328:165–83
    [Google Scholar]
  88. Mitsikostas DD, Sanchez del Rio M, Moskowitz MA, Waeber C 1999. Both 5-HT1B and 5-HT1F receptors modulate c-fos expression within rat trigeminal nucleus caudalis. Eur. J. Pharmacol. 369:271–77
    [Google Scholar]
  89. Mollgard K, Beinlich FRM, Kusk P, Miyakoshi LM, Delle C et al. 2023. A mesothelium divides the subarachnoid space into functional compartments. Science 379:84–88
    [Google Scholar]
  90. Moskowitz MA. 1984. The neurobiology of vascular head pain. Ann. Neurol. 16:157–68
    [Google Scholar]
  91. Moskowitz MA. 1993. Neurogenic inflammation in the pathophysiology and treatment of migraine. Neurology 43:S16–20
    [Google Scholar]
  92. Moskowitz MA, Cutrer FM. 1993. SUMATRIPTAN: a receptor-targeted treatment for migraine. Annu. Rev. Med. 44:145–54
    [Google Scholar]
  93. Moskowitz MA, Reinhard JF Jr., Romero J, Melamed E, Pettibone DJ. 1979. Neurotransmitters and the fifth cranial nerve: Is there a relation to the headache phase of migraine?. Lancet 2:883–85
    [Google Scholar]
  94. Murthy SE, Loud MC, Daou I, Marshall KL, Schwaller F et al. 2018. The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain in mice. Sci. Transl. Med. 10:eaat9897
    [Google Scholar]
  95. Nassini R, Materazzi S, Vriens J, Prenen J, Benemei S et al. 2012. The ‘headache tree’ via umbellulone and TRPA1 activates the trigeminovascular system. Brain 135:376–90
    [Google Scholar]
  96. O'Connor TP, van der Kooy D. 1986. Pattern of intracranial and extracranial projections of trigeminal ganglion cells. J. Neurosci. 6:2200–7
    [Google Scholar]
  97. Oshinsky ML, Gomonchareonsiri S. 2007. Episodic dural stimulation in awake rats: a model for recurrent headache. Headache 47:1026–36
    [Google Scholar]
  98. Patapoutian A, Peier AM, Story GM, Viswanath V. 2003. ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat. Rev. Neurosci. 4:529–39
    [Google Scholar]
  99. Petersen KA, Birk S, Doods H, Edvinsson L, Olesen J. 2004. Inhibitory effect of BIBN4096BS on cephalic vasodilatation induced by CGRP or transcranial electrical stimulation in the rat. Br. J. Pharmacol. 143:697–704
    [Google Scholar]
  100. Phebus LA, Johnson KW, Zgombick JM, Gilbert PJ, Van Belle K et al. 1997. Characterization of LY344864 as a pharmacological tool to study 5-HT1F receptors: binding affinities, brain penetration and activity in the neurogenic dural inflammation model of migraine. Life Sci. 61:2117–26
    [Google Scholar]
  101. Pietrobon D, Brennan KC. 2019. Genetic mouse models of migraine. J. Headache Pain 20:79
    [Google Scholar]
  102. Pietrobon D, Moskowitz MA. 2014. Chaos and commotion in the wake of cortical spreading depression and spreading depolarizations. Nat. Rev. Neurosci. 15:379–93
    [Google Scholar]
  103. Pulous FE, Cruz-Hernandez JC, Yang C, Kaya Z, Paccalet A et al. 2022. Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis. Nat. Neurosci. 25:567–76
    [Google Scholar]
  104. Ray BS, Wolff HG. 1940. Experimental studies on headache: pain sensitive structures of the head and their significance in headache. Arch. Surg. 41:813–56
    [Google Scholar]
  105. Reeh PW, Petho G. 2000. Nociceptor excitation by thermal sensitization—a hypothesis. Prog. Brain Res. 129:39–50
    [Google Scholar]
  106. Reuter U, Bolay H, Jansen-Olesen I, Chiarugi A, Sanchez del Rio M et al. 2001. Delayed inflammation in rat meninges: implications for migraine pathophysiology. Brain 124:2490–502
    [Google Scholar]
  107. Reuter U, Chiarugi A, Bolay H, Moskowitz MA. 2002. Nuclear factor-κB as a molecular target for migraine therapy. Ann. Neurol. 51:507–16
    [Google Scholar]
  108. Ringstad G, Eide PK. 2020. Cerebrospinal fluid tracer efflux to parasagittal dura in humans. Nat. Commun. 11:354
    [Google Scholar]
  109. Rosic B, Dukefoss DB, Abjorsbraten KS, Tang W, Jensen V et al. 2019. Aquaporin-4-independent volume dynamics of astroglial endfeet during cortical spreading depression. Glia 67:1113–21
    [Google Scholar]
  110. Roth TL, Nayak D, Atanasijevic T, Koretsky AP, Latour LL, McGavern DB. 2014. Transcranial amelioration of inflammation and cell death after brain injury. Nature 505:223–28
    [Google Scholar]
  111. Rustenhoven J, Drieu A, Mamuladze T, de Lima KA, Dykstra T et al. 2021. Functional characterization of the dural sinuses as a neuroimmune interface. Cell 184:1000–16.e27
    [Google Scholar]
  112. Schain AJ, Melo-Carrillo A, Borsook D, Grutzendler J, Strassman AM, Burstein R. 2018. Activation of pial and dural macrophages and dendritic cells by cortical spreading depression. Ann. Neurol. 83:508–21
    [Google Scholar]
  113. Schain AJ, Melo-Carrillo A, Strassman AM, Burstein R. 2017. Cortical spreading depression closes paravascular space and impairs glymphatic flow: implications for migraine headache. J. Neurosci. 37:2904–15
    [Google Scholar]
  114. Schain AJ, Melo-Carrillo A, Stratton J, Strassman AM, Burstein R. 2019. CSD-induced arterial dilatation and plasma protein extravasation are unaffected by fremanezumab: implications for CGRP's role in migraine with aura. J. Neurosci. 39:6001–11
    [Google Scholar]
  115. Schock SC, Munyao N, Yakubchyk Y, Sabourin LA, Hakim AM et al. 2007. Cortical spreading depression releases ATP into the extracellular space and purinergic receptor activation contributes to the induction of ischemic tolerance. Brain Res. 1168:129–38
    [Google Scholar]
  116. Schoonman GG, van der Grond J, Kortmann C, van der Geest RJ, Terwindt GM, Ferrari MD. 2008. Migraine headache is not associated with cerebral or meningeal vasodilatation—a 3T magnetic resonance angiography study. Brain 131:2192–200
    [Google Scholar]
  117. Schueler M, Messlinger K, Dux M, Neuhuber WL, De Col R. 2013. Extracranial projections of meningeal afferents and their impact on meningeal nociception and headache. Pain 154:1622–31
    [Google Scholar]
  118. Storer RJ, Akerman S, Goadsby PJ. 2004. Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat. Br. J. Pharmacol. 142:1171–81
    [Google Scholar]
  119. Storer RJ, Goadsby PJ. 1997. Microiontophoretic application of serotonin (5HT)1B/1D agonists inhibits trigeminal cell firing in the cat. Brain 120:2171–77
    [Google Scholar]
  120. Strassman AM, Levy D. 2006. Response properties of dural nociceptors in relation to headache. J. Neurophysiol. 95:1298–306
    [Google Scholar]
  121. Strassman AM, Melo-Carrillo A, Houle TT, Adams A, Brin MF, Burstein R. 2022. Atogepant—an orally-administered CGRP antagonist—attenuates activation of meningeal nociceptors by CSD. Cephalalgia 42:933–43
    [Google Scholar]
  122. Strassman AM, Raymond SA. 1999. Electrophysiological evidence for tetrodotoxin-resistant sodium channels in slowly conducting dural sensory fibers. J. Neurophysiol. 81:413–24
    [Google Scholar]
  123. Strassman AM, Raymond SA, Burstein R. 1996. Sensitization of meningeal sensory neurons and the origin of headaches. Nature 384:560–64
    [Google Scholar]
  124. Strassman AM, Weissner W, Williams M, Ali S, Levy D 2004. Axon diameters and intradural trajectories of the dural innervation in the rat. J. Comp. Neurol. 473:364–76
    [Google Scholar]
  125. Takizawa T, Qin T, Lopes de Morais A, Sugimoto K, Chung JY et al. 2020. Non-invasively triggered spreading depolarizations induce a rapid pro-inflammatory response in cerebral cortex. J. Cereb. Blood Flow Metab. 40:1117–31
    [Google Scholar]
  126. Tvedskov JF, Tfelt-Hansen P, Petersen KA, Jensen LT, Olesen J. 2010. CGRP receptor antagonist olcegepant (BIBN4096BS) does not prevent glyceryl trinitrate-induced migraine. Cephalalgia 30:1346–53
    [Google Scholar]
  127. Van Hove H, Martens L, Scheyltjens I, De Vlaminck K, Pombo Antunes AR et al. 2019. A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. Nat. Neurosci. 22:1021–35
    [Google Scholar]
  128. Vaughn AH, Gold MS. 2010. Ionic mechanisms underlying inflammatory mediator-induced sensitization of dural afferents. J. Neurosci. 30:7878–88
    [Google Scholar]
  129. Viana M, Linde M, Sances G, Ghiotto N, Guaschino E et al. 2016. Migraine aura symptoms: duration, succession and temporal relationship to headache. Cephalalgia 36:413–21
    [Google Scholar]
  130. von Buchholtz LJ, Lam RM, Emrick JJ, Chesler AT, Ryba NJP. 2020. Assigning transcriptomic class in the trigeminal ganglion using multiplex in situ hybridization and machine learning. Pain 161:2212–24
    [Google Scholar]
  131. Waeber C, Moskowitz MA. 1995. [3H]sumatriptan labels both 5-HT1D and 5-HT1F receptor binding sites in the guinea pig brain: an autoradiographic study. Naunyn-Schmiedeberg's Arch. Pharmacol. 352:263–75
    [Google Scholar]
  132. Wei X, Edelmayer RM, Yan J, Dussor G 2011. Activation of TRPV4 on dural afferents produces headache-related behavior in a preclinical rat model. Cephalalgia 31:1595–600
    [Google Scholar]
  133. Yan J, Edelmayer RM, Wei X, De Felice M, Porreca F, Dussor G. 2011. Dural afferents express acid-sensing ion channels: a role for decreased meningeal pH in migraine headache. Pain 152:106–13
    [Google Scholar]
  134. Yan J, Melemedjian OK, Price TJ, Dussor G. 2012. Sensitization of dural afferents underlies migraine-related behavior following meningeal application of interleukin-6 (IL-6). Mol. Pain 8:6
    [Google Scholar]
  135. Yang L, Xu M, Bhuiyan SA, Li J, Zhao J et al. 2022. Human and mouse trigeminal ganglia cell atlas implicates multiple cell types in migraine. Neuron 110:1806–21.e8
    [Google Scholar]
  136. Zeller J, Poulsen KT, Sutton JE, Abdiche YN, Collier S et al. 2008. CGRP function-blocking antibodies inhibit neurogenic vasodilatation without affecting heart rate or arterial blood pressure in the rat. Br. J. Pharmacol. 155:1093–103
    [Google Scholar]
  137. Zhang X, Burstein R, Levy D. 2012. Local action of the proinflammatory cytokines IL-1β and IL-6 on intracranial meningeal nociceptors. Cephalalgia 32:66–72
    [Google Scholar]
  138. Zhang X, Kainz V, Burstein R, Levy D. 2011. Tumor necrosis factor-α induces sensitization of meningeal nociceptors mediated via local COX and p38 MAP kinase actions. Pain 152:140–49
    [Google Scholar]
  139. Zhang X, Kainz V, Zhao J, Strassman AM, Levy D. 2013. Vascular extracellular signal-regulated kinase mediates migraine-related sensitization of meningeal nociceptors. Ann. Neurol. 73:741–50
    [Google Scholar]
  140. Zhang X, Levy D. 2008. Modulation of meningeal nociceptors mechanosensitivity by peripheral proteinase-activated receptor-2: the role of mast cells. Cephalalgia 28:276–84
    [Google Scholar]
  141. 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. 30:8807–14
    [Google Scholar]
  142. Zhang X, Strassman AM, Burstein R, Levy D. 2007. Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. J. Pharmacol. Exp. Ther. 322:806–12
    [Google Scholar]
  143. Zhao J, Blaeser AS, Levy D. 2021. Astrocytes mediate migraine-related intracranial meningeal mechanical hypersensitivity. Pain 162:2386–96
    [Google Scholar]
  144. Zhao J, Bree D, Harrington MG, Strassman AM, Levy D. 2017. Cranial dural permeability of inflammatory nociceptive mediators: potential implications for animal models of migraine. Cephalalgia 37:1017–25
    [Google Scholar]
  145. Zhao J, Levy D. 2014. The sensory innervation of the calvarial periosteum is nociceptive and contributes to headache-like behavior. Pain 155:1392–400
    [Google Scholar]
  146. Zhao J, Levy D. 2015. Modulation of intracranial meningeal nociceptor activity by cortical spreading depression: a reassessment. J. Neurophysiol. 113:2778–85
    [Google Scholar]
  147. Zhao J, Levy D. 2016. Cortical spreading depression promotes persistent mechanical sensitization of intracranial meningeal afferents: implications for the intracranial mechanosensitivity of migraine. eNeuro 3:ENEURO.0287–16.2016
    [Google Scholar]
  148. Zhao J, Levy D. 2018a. The CGRP receptor antagonist BIBN4096 inhibits prolonged meningeal afferent activation evoked by brief local K+ stimulation but not cortical spreading depression-induced afferent sensitization. Pain Rep. 3:e632
    [Google Scholar]
  149. Zhao J, Levy D. 2018b. Dissociation between CSD-evoked metabolic perturbations and meningeal afferent activation and sensitization: implications for mechanisms of migraine headache onset. J. Neurosci. 38:5053–66
    [Google Scholar]
  150. Zhou N, Rungta RL, Malik A, Han H, Wu DC, MacVicar BA. 2013. Regenerative glutamate release by presynaptic NMDA receptors contributes to spreading depression. J. Cereb. Blood Flow Metab. 33:1582–94
    [Google Scholar]
/content/journals/10.1146/annurev-neuro-080422-105509
Loading
/content/journals/10.1146/annurev-neuro-080422-105509
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error