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Semin Neurol 2022; 42(04): 459-473
DOI: 10.1055/s-0042-1757924
Review Article

Anatomy and Physiology of Headache

Andrea M. Harriott
1   Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
,
Yulia Orlova
2   Department of Neurology, University of Florida, Gainesville, Florida
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Abstract

Headache disorders can produce recurrent, incapacitating pain. Migraine and cluster headache are notable for their ability to produce significant disability. The anatomy and physiology of headache disorders is fundamental to evolving treatment approaches and research priorities. Key concepts in headache mechanisms include activation and sensitization of trigeminovascular, brainstem, thalamic, and hypothalamic neurons; modulation of cortical brain regions; and activation of descending pain circuits. This review will examine the relevant anatomy of the trigeminal, brainstem, subcortical, and cortical brain regions and concepts related to the pathophysiology of migraine and cluster headache disorders.

Keywords

headache - trigeminovascular afferent - migraine - cluster headache


Publication History

Article published online:
02 November 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
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  • References

  • 1 Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007; 68 (05) 343-349
    CrossrefPubMedGoogle Scholar
  • 2 GBD 2016 Headache Collaborators. 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 2018; 17 (11) 954-976
    CrossrefPubMedGoogle Scholar
  • 3 Stovner Lj, Hagen K, Jensen R. et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia 2007; 27 (03) 193-210
    CrossrefPubMedGoogle Scholar
  • 4 Finkel AG. Epidemiology of cluster headache. Curr Pain Headache Rep 2003; 7 (02) 144-149
    CrossrefPubMedGoogle Scholar
  • 5 Ray B, Wolff H. Experimental studies on headache: pain-sensitive structures of the head and their significance in headache. Arch Surg 1940; 41 (04) 813-856
    CrossrefPubMedGoogle Scholar
  • 6 Strassman AM, Raymond SA, Burstein R. Sensitization of meningeal sensory neurons and the origin of headaches. Nature 1996; 384 (6609): 560-564
    CrossrefPubMedGoogle Scholar
  • 7 Levy D, Strassman AM. Mechanical response properties of A and C primary afferent neurons innervating the rat intracranial dura. J Neurophysiol 2002; 88 (06) 3021-3031
    CrossrefPubMedGoogle Scholar
  • 8 Noseda R, Burstein R. Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain. Pain 2013; 154 (Suppl. 01) 1-21
    PubMedGoogle Scholar
  • 9 Barbanti P, Fabbrini G, Pesare M, Vanacore N, Cerbo R. Unilateral cranial autonomic symptoms in migraine. Cephalalgia 2002; 22 (04) 256-259
    CrossrefPubMedGoogle Scholar
  • 10 Drummond PD. Autonomic disturbances in cluster headache. Brain 1988; 111 (Pt 5): 1199-1209
    CrossrefPubMedGoogle Scholar
  • 11 Arbab MA, Wiklund L, Svendgaard NA. Origin and distribution of cerebral vascular innervation from superior cervical, trigeminal and spinal ganglia investigated with retrograde and anterograde WGA-HRP tracing in the rat. Neuroscience 1986; 19 (03) 695-708
    CrossrefPubMedGoogle Scholar
  • 12 Keller JT, Saunders MC, Beduk A, Jollis JG. Innervation of the posterior fossa dura of the cat. Brain Res Bull 1985; 14 (01) 97-102
    CrossrefPubMedGoogle Scholar
  • 13 Noseda R, Melo-Carrillo A, Nir RR, Strassman AM, Burstein R. Non-trigeminal nociceptive innervation of the posterior dura: implications to occipital headache. J Neurosci 2019; 39 (10) 1867-1880
    CrossrefPubMedGoogle Scholar
  • 14 Liu Y, Broman J, Edvinsson L. Central projections of the sensory innervation of the rat middle meningeal artery. Brain Res 2008; 1208: 103-110
    CrossrefPubMedGoogle Scholar
  • 15 Kosaras B, Jakubowski M, Kainz V, Burstein R. Sensory innervation of the calvarial bones of the mouse. J Comp Neurol 2009; 515 (03) 331-348
    PubMedGoogle Scholar
  • 16 Zhao J, Levy D. The sensory innervation of the calvarial periosteum is nociceptive and contributes to headache-like behavior. Pain 2014; 155 (07) 1392-1400
    CrossrefPubMedGoogle Scholar
  • 17 Schueler M, Messlinger K, Dux M, Neuhuber WL, De R. Extracranial projections of meningeal afferents and their impact on meningeal nociception and headache. Pain 2013; 154 (09) 1622-1631
    CrossrefPubMedGoogle Scholar
  • 18 Roland J, Bernard C, Bracard S. et al. Microvascularization of the intracranial dura mater. Surg Radiol Anat 1987; 9 (01) 43-49
    CrossrefPubMedGoogle Scholar
  • 19 Bonasia S, Smajda S, Ciccio G, Robert T. Middle meningeal artery: anatomy and variations. AJNR Am J Neuroradiol 2020; 41 (10) 1777-1785
    CrossrefPubMedGoogle Scholar
  • 20 Messlinger K, Balcziak LK, Russo AF. Cross-talk signaling in the trigeminal ganglion: role of neuropeptides and other mediators. J Neural Transm (Vienna) 2020; 127 (04) 431-444
    CrossrefPubMedGoogle Scholar
  • 21 Tajti J, Szok D, Majláth Z, Tuka B, Csáti A, Vécsei L. Migraine and neuropeptides. Neuropeptides 2015; 52: 19-30
    CrossrefPubMedGoogle Scholar
  • 22 Lazarov NE. Comparative analysis of the chemical neuroanatomy of the mammalian trigeminal ganglion and mesencephalic trigeminal nucleus. Prog Neurobiol 2002; 66 (01) 19-59
    CrossrefPubMedGoogle Scholar
  • 23 Shimazaki K, Yajima T, Ichikawa H, Sato T. Distribution and possible function of galanin about headache and immune system in the rat dura mater. Sci Rep 2022; 12 (01) 5206
    CrossrefPubMedGoogle Scholar
  • 24 Quartu M, Del Fiacco M. Enkephalins occur and colocalize with substance P in human trigeminal ganglion neurones. Neuroreport 1994; 5 (04) 465-468
    CrossrefPubMedGoogle Scholar
  • 25 Imboden H, Patil J, Nussberger J. et al. Endogenous angiotensinergic system in neurons of rat and human trigeminal ganglia. Regul Pept 2009; 154 (1-3): 23-31
    CrossrefPubMedGoogle Scholar
  • 26 Nakamura M, Jang IS. Characterization of dural afferent neurons innervating cranial blood vessels within the dura in rats. Brain Res 2018; 1696: 91-102
    CrossrefPubMedGoogle Scholar
  • 27 Kaiser EA, Kuburas A, Recober A, Russo AF. Modulation of CGRP-induced light aversion in wild-type mice by a 5-HT(1B/D) agonist. J Neurosci 2012; 32 (44) 15439-15449
    CrossrefPubMedGoogle Scholar
  • 28 Recober A, Kaiser EA, Kuburas A, Russo AF. Induction of multiple photophobic behaviors in a transgenic mouse sensitized to CGRP. Neuropharmacology 2010; 58 (01) 156-165
    CrossrefPubMedGoogle Scholar
  • 29 Mason BN, Kaiser EA, Kuburas A. et al. Induction of migraine-like photophobic behavior in mice by both peripheral and central CGRP mechanisms. J Neurosci 2017; 37 (01) 204-216
    CrossrefPubMedGoogle Scholar
  • 30 De Logu F, Landini L, Janal MN. et al. Migraine-provoking substances evoke periorbital allodynia in mice. J Headache Pain 2019; 20 (01) 18
    CrossrefPubMedGoogle Scholar
  • 31 Rea BJ, Wattiez AS, Waite JS. et al. Peripherally administered calcitonin gene-related peptide induces spontaneous pain in mice: implications for migraine. Pain 2018; 159 (11) 2306-2317
    CrossrefPubMedGoogle Scholar
  • 32 Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia 2002; 22 (01) 54-61
    CrossrefPubMedGoogle Scholar
  • 33 Vollesen ALH, Snoer A, Beske RP. et al. Effect of infusion of calcitonin gene-related peptide on cluster headache attacks: a randomized clinical trial. JAMA Neurol 2018; 75 (10) 1187-1197
    CrossrefPubMedGoogle Scholar
  • 34 Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990; 28 (02) 183-187
    CrossrefPubMedGoogle Scholar
  • 35 Gallai V, Sarchielli P, Floridi A. et al. Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally. Cephalalgia 1995; 15 (05) 384-390
    CrossrefPubMedGoogle Scholar
  • 36 Sarchielli P, Alberti A, Codini M, Floridi A, Gallai V. Nitric oxide metabolites, prostaglandins and trigeminal vasoactive peptides in internal jugular vein blood during spontaneous migraine attacks. Cephalalgia 2000; 20 (10) 907-918
    CrossrefPubMedGoogle Scholar
  • 37 Messlinger K, Hanesch U, Baumgärtel M, Trost B, Schmidt RF. Innervation of the dura mater encephali of cat and rat: ultrastructure and calcitonin gene-related peptide-like and substance P-like immunoreactivity. Anat Embryol (Berl) 1993; 188 (03) 219-237
    CrossrefPubMedGoogle Scholar
  • 38 Edvinsson L, Tajti J, Szalárdy L, Vécsei L. PACAP and its role in primary headaches. J Headache Pain 2018; 19 (01) 21
    CrossrefPubMedGoogle Scholar
  • 39 Amin FM, Hougaard A, Schytz HW. et al. Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38. Brain 2014; 137 (Pt 3): 779-794
    CrossrefPubMedGoogle Scholar
  • 40 Pellesi L, Al-Karagholi MA, De Icco R. et al. Effect of vasoactive intestinal polypeptide on development of migraine headaches: a randomized clinical trial. JAMA Netw Open 2021; 4 (08) e2118543
    CrossrefPubMedGoogle Scholar
  • 41 Waschek JA, Baca SM, Akerman S. PACAP and migraine headache: immunomodulation of neural circuits in autonomic ganglia and brain parenchyma. J Headache Pain 2018; 19 (01) 23
    CrossrefPubMedGoogle Scholar
  • 42 Sundrum T, Walker CS. Pituitary adenylate cyclase-activating polypeptide receptors in the trigeminovascular system: implications for migraine. Br J Pharmacol 2018; 175 (21) 4109-4120
    CrossrefPubMedGoogle Scholar
  • 43 Edvinsson L, Elsås T, Suzuki N, Shimizu T, Lee TJ. Origin and co-localization of nitric oxide synthase, CGRP, PACAP, and VIP in the cerebral circulation of the rat. Microsc Res Tech 2001; 53 (03) 221-228
    CrossrefPubMedGoogle Scholar
  • 44 Ashina M, Bendtsen L, Jensen R, Olesen J. Nitric oxide-induced headache in patients with chronic tension-type headache. Brain 2000; 123 (Pt 9): 1830-1837
    CrossrefPubMedGoogle Scholar
  • 45 Ekbom K, Sjöstrand C, Svensson DA, Waldenlind E. Periods of cluster headache induced by nitrate therapy and spontaneous remission of angina pectoris during active clusters. Cephalalgia 2004; 24 (02) 92-98
    CrossrefPubMedGoogle Scholar
  • 46 Pradhan AA, Smith ML, McGuire B, Tarash I, Evans CJ, Charles A. Characterization of a novel model of chronic migraine. Pain 2014; 155 (02) 269-274
    CrossrefPubMedGoogle Scholar
  • 47 Lafrenière RG, Cader MZ, Poulin JF. et al. A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura. Nat Med 2010; 16 (10) 1157-1160
    CrossrefPubMedGoogle Scholar
  • 48 Liu P, Xiao Z, Ren F. et al. Functional analysis of a migraine-associated TRESK K+ channel mutation. J Neurosci 2013; 33 (31) 12810-12824
    CrossrefPubMedGoogle Scholar
  • 49 Andres-Enguix I, Shang L, Stansfeld PJ. et al. Functional analysis of missense variants in the TRESK (KCNK18) K channel. Sci Rep 2012; 2: 237
    CrossrefPubMedGoogle Scholar
  • 50 Wulf-Johansson H, Amrutkar DV, Hay-Schmidt A. et al. Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway. Neuroscience 2010; 167 (04) 1091-1102
    CrossrefPubMedGoogle Scholar
  • 51 Al-Karagholi MA, Ghanizada H, Waldorff Nielsen CA. et al. Opening of BKCa channels causes migraine attacks: a new downstream target for the treatment of migraine. Pain 2021; 162 (10) 2512-2520
    PubMedGoogle Scholar
  • 52 Al-Karagholi MA, Hansen JM, Guo S, Olesen J, Ashina M. Opening of ATP-sensitive potassium channels causes migraine attacks: a new target for the treatment of migraine. Brain 2019; 142 (09) 2644-2654
    CrossrefPubMedGoogle Scholar
  • 53 Coskun H, Elbahi FA, Al-Karagholi MA, Ghanizada H, Sheykhzade M, Ashina M. The effect of K ATP channel blocker glibenclamide on CGRP-induced headache and hemodynamic in healthy volunteers. Front Physiol 2021; 12: 652136
    CrossrefPubMedGoogle Scholar
  • 54 Vaughn AH, Gold MS. Ionic mechanisms underlying inflammatory mediator-induced sensitization of dural afferents. J Neurosci 2010; 30 (23) 7878-7888
    CrossrefPubMedGoogle Scholar
  • 55 Tottene A, Pivotto F, Fellin T, Cesetti T, van den Maagdenberg AM, Pietrobon D. Specific kinetic alterations of human CaV2.1 calcium channels produced by mutation S218L causing familial hemiplegic migraine and delayed cerebral edema and coma after minor head trauma. J Biol Chem 2005; 280 (18) 17678-17686
    CrossrefPubMedGoogle Scholar
  • 56 Pietrobon D. Calcium channels and migraine. Biochim Biophys Acta 2013; 1828 (07) 1655-1665
    CrossrefPubMedGoogle Scholar
  • 57 Tao J, Liu P, Xiao Z, Zhao H, Gerber BR, Cao YQ. Effects of familial hemiplegic migraine type 1 mutation T666M on voltage-gated calcium channel activities in trigeminal ganglion neurons. J Neurophysiol 2012; 107 (06) 1666-1680
    CrossrefPubMedGoogle Scholar
  • 58 Amrutkar DV, Ploug KB, Olesen J, Jansen-Olesen I. Role for voltage gated calcium channels in calcitonin gene-related peptide release in the rat trigeminovascular system. Neuroscience 2011; 172: 510-517
    CrossrefPubMedGoogle Scholar
  • 59 Xiao Y, Richter JA, Hurley JH. Release of glutamate and CGRP from trigeminal ganglion neurons: role of calcium channels and 5-HT1 receptor signaling. Mol Pain 2008; 4: 12
    CrossrefPubMedGoogle Scholar
  • 60 Shields KG, Storer RJ, Akerman S, Goadsby PJ. Calcium channels modulate nociceptive transmission in the trigeminal nucleus of the cat. Neuroscience 2005; 135 (01) 203-212
    CrossrefPubMedGoogle Scholar
  • 61 Karsan N, Gonzales EB, Dussor G. Targeted acid-sensing ion channel therapies for migraine. Neurotherapeutics 2018; 15 (02) 402-414
    CrossrefPubMedGoogle Scholar
  • 62 Yan J, Edelmayer RM, Wei X, De Felice M, Porreca F, Dussor G. Dural afferents express acid-sensing ion channels: a role for decreased meningeal pH in migraine headache. Pain 2011; 152 (01) 106-113
    CrossrefPubMedGoogle Scholar
  • 63 Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosci 2015; 35 (17) 6619-6629
    CrossrefPubMedGoogle Scholar
  • 64 Mikhailov N, Leskinen J, Fagerlund I. et al. Mechanosensitive meningeal nociception via Piezo channels: implications for pulsatile pain in migraine?. Neuropharmacology 2019; 149: 113-123
    CrossrefPubMedGoogle Scholar
  • 65 McIlvried LA, Cruz JA, Borghesi LA, Gold MS. Sex-, stress-, and sympathetic post-ganglionic-dependent changes in identity and proportions of immune cells in the dura. Cephalalgia 2017; 37 (01) 36-48
    CrossrefPubMedGoogle Scholar
  • 66 Schain AJ, Melo-Carrillo A, Borsook D, Grutzendler J, Strassman AM, Burstein R. Activation of pial and dural macrophages and dendritic cells by cortical spreading depression. Ann Neurol 2018; 83 (03) 508-521
    CrossrefPubMedGoogle Scholar
  • 67 Hanani M. Satellite glial cells in sensory ganglia: from form to function. Brain Res Brain Res Rev 2005; 48 (03) 457-476
    CrossrefPubMedGoogle Scholar
  • 68 Boye Larsen D, Ingemann Kristensen G, Panchalingam V. et al. Investigating the expression of metabotropic glutamate receptors in trigeminal ganglion neurons and satellite glial cells: implications for craniofacial pain. J Recept Signal Transduct Res 2014; 34 (04) 261-269
    CrossrefPubMedGoogle Scholar
  • 69 Afroz S, Arakaki R, Iwasa T. et al. CGRP induces differential regulation of cytokines from satellite glial cells in trigeminal ganglia and orofacial nociception. Int J Mol Sci 2019; 20 (03) E711
    CrossrefPubMedGoogle Scholar
  • 70 Li J, Vause CV, Durham PL. Calcitonin gene-related peptide stimulation of nitric oxide synthesis and release from trigeminal ganglion glial cells. Brain Res 2008; 1196: 22-32
    CrossrefPubMedGoogle Scholar
  • 71 Yang L, Xu M, Bhuiyan SA. et al. Human and mouse trigeminal ganglia cell atlas implicates multiple cell types in migraine. Neuron 2022; 110 (11) 1806-1821.e8
    CrossrefPubMedGoogle Scholar
  • 72 Davis KD, Dostrovsky JO. Responses of feline trigeminal spinal tract nucleus neurons to stimulation of the middle meningeal artery and sagittal sinus. J Neurophysiol 1988; 59 (02) 648-666
    CrossrefPubMedGoogle Scholar
  • 73 Hoskin KL, Zagami AS, Goadsby PJ. Stimulation of the middle meningeal artery leads to Fos expression in the trigeminocervical nucleus: a comparative study of monkey and cat. J Anat 1999; 194 (Pt 4): 579-588
    CrossrefPubMedGoogle Scholar
  • 74 Strassman AM, Mineta Y, Vos BP. Distribution of fos-like immunoreactivity in the medullary and upper cervical dorsal horn produced by stimulation of dural blood vessels in the rat. J Neurosci 1994; 14 (06) 3725-3735
    CrossrefPubMedGoogle Scholar
  • 75 Kaube H, Keay KA, Hoskin KL, Bandler R, Goadsby PJ. Expression of c-Fos-like immunoreactivity in the caudal medulla and upper cervical spinal cord following stimulation of the superior sagittal sinus in the cat. Brain Res 1993; 629 (01) 95-102
    CrossrefPubMedGoogle Scholar
  • 76 Selzer M, Spencer WA. Convergence of visceral and cutaneous afferent pathways in the lumbar spinal cord. Brain Res 1969; 14 (02) 331-348
    CrossrefPubMedGoogle Scholar
  • 77 Bartsch T, Goadsby PJ. Stimulation of the greater occipital nerve induces increased central excitability of dural afferent input. Brain 2002; 125 (Pt 7): 1496-1509
    CrossrefPubMedGoogle Scholar
  • 78 Waeber C, Moskowitz MA. Migraine as an inflammatory disorder. Neurology 2005; 64 (10, Suppl 2): S9-S15
    CrossrefPubMedGoogle Scholar
  • 79 Moskowitz MA, Reinhard Jr JF, Romero J, Melamed E, Pettibone DJ. Neurotransmitters and the fifth cranial nerve: is there a relation to the headache phase of migraine?. Lancet 1979; 2 (8148): 883-885
    CrossrefPubMedGoogle Scholar
  • 80 Edvinsson L, Haanes KA, Warfvinge K. Does inflammation have a role in migraine?. Nat Rev Neurol 2019; 15 (08) 483-490
    CrossrefPubMedGoogle Scholar
  • 81 Ottosson A, Edvinsson L. Release of histamine from dural mast cells by substance P and calcitonin gene-related peptide. Cephalalgia 1997; 17 (03) 166-174
    CrossrefPubMedGoogle Scholar
  • 82 Markowitz S, Saito K, Moskowitz MA. Neurogenically mediated plasma extravasation in dura mater: effect of ergot alkaloids. A possible mechanism of action in vascular headache. Cephalalgia 1988; 8 (02) 83-91
    CrossrefPubMedGoogle Scholar
  • 83 Ebersberger A, Averbeck B, Messlinger K, Reeh PW. Release of substance P, calcitonin gene-related peptide and prostaglandin E2 from rat dura mater encephali following electrical and chemical stimulation in vitro. Neuroscience 1999; 89 (03) 901-907
    CrossrefPubMedGoogle Scholar
  • 84 O'Shaughnessy CT, Connor HE. Investigation of the role of tachykinin NK1, NK2 receptors and CGRP receptors in neurogenic plasma protein extravasation in dura mater. Eur J Pharmacol 1994; 263 (1-2): 193-198
    CrossrefPubMedGoogle Scholar
  • 85 Markowitz S, Saito K, Moskowitz MA. Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain. J Neurosci 1987; 7 (12) 4129-4136
    CrossrefPubMedGoogle Scholar
  • 86 Lee WS, Moussaoui SM, Moskowitz MA. 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 1994; 112 (03) 920-924
    CrossrefPubMedGoogle Scholar
  • 87 Goldstein DJ, Wang O, Saper JR, Stoltz R, Silberstein SD, Mathew NT. Ineffectiveness of neurokinin-1 antagonist in acute migraine: a crossover study. Cephalalgia 1997; 17 (07) 785-790
    CrossrefPubMedGoogle Scholar
  • 88 Roon KI, Olesen J, Diener HC. et al. No acute antimigraine efficacy of CP-122,288, a highly potent inhibitor of neurogenic inflammation: results of two randomized, double-blind, placebo-controlled clinical trials. Ann Neurol 2000; 47 (02) 238-241
    CrossrefPubMedGoogle Scholar
  • 89 Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 1993; 33 (01) 48-56
    CrossrefPubMedGoogle Scholar
  • 90 Sarchielli P, Alberti A, Vaianella L. et al. Chemokine levels in the jugular venous blood of migraine without aura patients during attacks. Headache 2004; 44 (10) 961-968
    CrossrefPubMedGoogle Scholar
  • 91 Levy D, Burstein R, Kainz V, Jakubowski M, Strassman AM. Mast cell degranulation activates a pain pathway underlying migraine headache. Pain 2007; 130 (1-2): 166-176
    CrossrefPubMedGoogle Scholar
  • 92 Zhang XC, Kainz V, Burstein R, Levy D. Tumor necrosis factor-α induces sensitization of meningeal nociceptors mediated via local COX and p38 MAP kinase actions. Pain 2011; 152 (01) 140-149
    CrossrefPubMedGoogle Scholar
  • 93 Zhang X, Burstein R, Levy D. Local action of the proinflammatory cytokines IL-1β and IL-6 on intracranial meningeal nociceptors. Cephalalgia 2012; 32 (01) 66-72
    CrossrefPubMedGoogle Scholar
  • 94 Melo-Carrillo A, Lopez-Avila A. A chronic animal model of migraine, induced by repeated meningeal nociception, characterized by a behavioral and pharmacological approach. Cephalalgia 2013; 33 (13) 1096-1105
    CrossrefPubMedGoogle Scholar
  • 95 Burstein R, Yamamura H, Malick A, Strassman AM. Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J Neurophysiol 1998; 79 (02) 964-982
    CrossrefPubMedGoogle Scholar
  • 96 Mitsikostas DD, Sanchez del Rio M, Waeber C, Moskowitz MA, Cutrer FM. The NMDA receptor antagonist MK-801 reduces capsaicin-induced c-fos expression within rat trigeminal nucleus caudalis. Pain 1998; 76 (1-2): 239-248
    CrossrefPubMedGoogle Scholar
  • 97 Andreou AP, Holland PR, Lasalandra MP, Goadsby PJ. Modulation of nociceptive dural input to the trigeminocervical complex through GluK1 kainate receptors. Pain 2015; 156 (03) 439-450
    CrossrefPubMedGoogle Scholar
  • 98 Noseda R, Monconduit L, Constandil L, Chalus M, Villanueva L. Central nervous system networks involved in the processing of meningeal and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in the rat. Cephalalgia 2008; 28 (08) 813-824
    CrossrefPubMedGoogle Scholar
  • 99 Chiang MC, Bowen A, Schier LA, Tupone D, Uddin O, Heinricher MM. Parabrachial complex: a hub for pain and aversion. J Neurosci 2019; 39 (42) 8225-8230
    CrossrefPubMedGoogle Scholar
  • 100 Campos CA, Bowen AJ, Roman CW, Palmiter RD. Encoding of danger by parabrachial CGRP neurons. Nature 2018; 555 (7698): 617-622
    CrossrefPubMedGoogle Scholar
  • 101 Malick A, Jakubowski M, Elmquist JK, Saper CB, Burstein R. A neurohistochemical blueprint for pain-induced loss of appetite. Proc Natl Acad Sci U S A 2001; 98 (17) 9930-9935
    CrossrefPubMedGoogle Scholar
  • 102 Uddin O, Anderson M, Smith J, Masri R, Keller A. Parabrachial complex processes dura inputs through a direct trigeminal ganglion-to-parabrachial connection. Neurobiol Pain 2021; 9: 100060
    CrossrefPubMedGoogle Scholar
  • 103 Hoskin KL, Bulmer DC, Lasalandra M, Jonkman A, Goadsby PJ. Fos expression in the midbrain periaqueductal grey after trigeminovascular stimulation. J Anat 2001; 198 (Pt 1): 29-35
    CrossrefPubMedGoogle Scholar
  • 104 Knight YE, Goadsby PJ. The periaqueductal grey matter modulates trigeminovascular input: a role in migraine?. Neuroscience 2001; 106 (04) 793-800
    CrossrefPubMedGoogle Scholar
  • 105 Pourrahimi AM, Abbasnejad M, Esmaeili-Mahani S, Kooshki R, Raoof M. Intra-periaqueductal gray matter administration of orexin-A exaggerates pulpitis-induced anxiogenic responses and c-fos expression mainly through the interaction with orexin 1 and cannabinoid 1 receptors in rats. Neuropeptides 2019; 73: 25-33
    CrossrefPubMedGoogle Scholar
  • 106 Pourrahimi AM, Abbasnejad M, Raoof M, Esmaeili-Mahani S, Kooshki R. The involvement of orexin 1 and cannabinoid 1 receptors within the ventrolateral periaqueductal gray matter in the modulation of migraine-induced anxiety and social behavior deficits of rats. Peptides 2021; 146: 170651
    CrossrefPubMedGoogle Scholar
  • 107 Lee HJ, Chang LY, Ho YC. et al. Stress induces analgesia via orexin 1 receptor-initiated endocannabinoid/CB1 signaling in the mouse periaqueductal gray. Neuropharmacology 2016; 105: 577-586
    CrossrefPubMedGoogle Scholar
  • 108 Chen Z, Chen X, Liu M, Liu S, Ma L, Yu S. Disrupted functional connectivity of periaqueductal gray subregions in episodic migraine. J Headache Pain 2017; 18 (01) 36
    CrossrefPubMedGoogle Scholar
  • 109 Mainero C, Boshyan J, Hadjikhani N. Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine. Ann Neurol 2011; 70 (05) 838-845
    CrossrefPubMedGoogle Scholar
  • 110 Guy N, Chalus M, Dallel R, Voisin DL. Both oral and caudal parts of the spinal trigeminal nucleus project to the somatosensory thalamus in the rat. Eur J Neurosci 2005; 21 (03) 741-754
    CrossrefPubMedGoogle Scholar
  • 111 Burstein R, Jakubowski M, Garcia-Nicas E. et al. Thalamic sensitization transforms localized pain into widespread allodynia. Ann Neurol 2010; 68 (01) 81-91
    CrossrefPubMedGoogle Scholar
  • 112 Noseda R, Kainz V, Borsook D, Burstein R. Neurochemical pathways that converge on thalamic trigeminovascular neurons: potential substrate for modulation of migraine by sleep, food intake, stress and anxiety. PLoS One 2014; 9 (08) e103929
    CrossrefPubMedGoogle Scholar
  • 113 Malick A, Burstein R. Cells of origin of the trigeminohypothalamic tract in the rat. J Comp Neurol 1998; 400 (01) 125-144
    CrossrefPubMedGoogle Scholar
  • 114 Malick A, Strassman RM, Burstein R. Trigeminohypothalamic and reticulohypothalamic tract neurons in the upper cervical spinal cord and caudal medulla of the rat. J Neurophysiol 2000; 84 (04) 2078-2112
    CrossrefPubMedGoogle Scholar
  • 115 Robert C, Bourgeais L, Arreto CD. et al. Paraventricular hypothalamic regulation of trigeminovascular mechanisms involved in headaches. J Neurosci 2013; 33 (20) 8827-8840
    CrossrefPubMedGoogle Scholar
  • 116 Benjamin L, Levy MJ, Lasalandra MP. et al. Hypothalamic activation after stimulation of the superior sagittal sinus in the cat: a Fos study. Neurobiol Dis 2004; 16 (03) 500-505
    CrossrefPubMedGoogle Scholar
  • 117 Schulte LH, Mehnert J, May A. Longitudinal neuroimaging over 30 days: temporal characteristics of migraine. Ann Neurol 2020; 87 (04) 646-651
    CrossrefPubMedGoogle Scholar
  • 118 May A, Burstein R. Hypothalamic regulation of headache and migraine. Cephalalgia 2019; 39 (13) 1710-1719
    CrossrefPubMedGoogle Scholar
  • 119 Denuelle M, Fabre N, Payoux P, Chollet F, Geraud G. Hypothalamic activation in spontaneous migraine attacks. Headache 2007; 47 (10) 1418-1426
    PubMedGoogle Scholar
  • 120 Abdallah K, Artola A, Monconduit L, Dallel R, Luccarini P. Bilateral descending hypothalamic projections to the spinal trigeminal nucleus caudalis in rats. PLoS One 2013; 8 (08) e73022
    CrossrefPubMedGoogle Scholar
  • 121 Holland PR, Akerman S, Goadsby PJ. Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat. Eur J Neurosci 2006; 24 (10) 2825-2833
    CrossrefPubMedGoogle Scholar
  • 122 Kooshki R, Abbasnejad M, Esmaeili-Mahani S, Raoof M, Sheibani V. Activation orexin 1 receptors in the ventrolateral periaqueductal gray matter attenuate nitroglycerin-induced migraine attacks and calcitonin gene related peptide up-regulation in trigeminal nucleus caudalis of rats. Neuropharmacology 2020; 178: 107981
    CrossrefPubMedGoogle Scholar
  • 123 Hoffmann J, Supronsinchai W, Akerman S. et al. Evidence for orexinergic mechanisms in migraine. Neurobiol Dis 2015; 74: 137-143
    CrossrefPubMedGoogle Scholar
  • 124 Chabi A, Zhang Y, Jackson S. et al. Randomized controlled trial of the orexin receptor antagonist filorexant for migraine prophylaxis. Cephalalgia 2015; 35 (05) 379-388
    CrossrefPubMedGoogle Scholar
  • 125 Goadsby PJ. Putting migraine to sleep: rexants as a preventive strategy. Cephalalgia 2015; 35 (05) 377-378
    CrossrefPubMedGoogle Scholar
  • 126 Warfvinge K, Krause D, Edvinsson L. The distribution of oxytocin and the oxytocin receptor in rat brain: relation to regions active in migraine. J Headache Pain 2020; 21 (01) 10
    CrossrefPubMedGoogle Scholar
  • 127 García-Boll E, Martínez-Lorenzana G, Condés-Lara M, González-Hernández A. Inhibition of nociceptive dural input to the trigeminocervical complex through oxytocinergic transmission. Exp Neurol 2020; 323: 113079
    CrossrefPubMedGoogle Scholar
  • 128 Wang Y, Pan Q, Tian R. et al. Repeated oxytocin prevents central sensitization by regulating synaptic plasticity via oxytocin receptor in a chronic migraine mouse model. J Headache Pain 2021; 22 (01) 84
    CrossrefPubMedGoogle Scholar
  • 129 Barbanti P, Aurilia C, Egeo G, Fofi L, Guadagni F, Ferroni P. Dopaminergic symptoms in migraine: a cross-sectional study on 1148 consecutive headache center-based patients. Cephalalgia 2020; 40 (11) 1168-1176
    CrossrefPubMedGoogle Scholar
  • 130 Coppola M, Yealy DM, Leibold RA. Randomized, placebo-controlled evaluation of prochlorperazine versus metoclopramide for emergency department treatment of migraine headache. Ann Emerg Med 1995; 26 (05) 541-546
    CrossrefPubMedGoogle Scholar
  • 131 Gaffigan ME, Bruner DI, Wason C, Pritchard A, Frumkin K. Intravenous Metoclopramide for Acute Migraine Therapy in the Emergency Department. A randomized controlled trial of intravenous haloperidol vs. J Emerg Med 2015; 49 (03) 326-334
    CrossrefPubMedGoogle Scholar
  • 132 Friedman BW, Esses D, Solorzano C. et al. A randomized controlled trial of prochlorperazine versus metoclopramide for treatment of acute migraine. Ann Emerg Med 2008; 52 (04) 399-406
    CrossrefPubMedGoogle Scholar
  • 133 Barraud Q, Obeid I, Aubert I. et al. Neuroanatomical study of the A11 diencephalospinal pathway in the non-human primate. PLoS One 2010; 5 (10) e13306
    CrossrefPubMedGoogle Scholar
  • 134 Bergerot A, Storer RJ, Goadsby PJ. Dopamine inhibits trigeminovascular transmission in the rat. Ann Neurol 2007; 61 (03) 251-262
    CrossrefPubMedGoogle Scholar
  • 135 Charbit AR, Akerman S, Holland PR, Goadsby PJ. Neurons of the dopaminergic/calcitonin gene-related peptide A11 cell group modulate neuronal firing in the trigeminocervical complex: an electrophysiological and immunohistochemical study. J Neurosci 2009; 29 (40) 12532-12541
    CrossrefPubMedGoogle Scholar
  • 136 DaSilva AF, Nascimento TD, Jassar H. et al. Dopamine D2/D3 imbalance during migraine attack and allodynia in vivo. Neurology 2017; 88 (17) 1634-1641
    CrossrefPubMedGoogle Scholar
  • 137 Leao A. Spreading depression of activity in the cerebral cortex. J Neurophysiol 1944; 7: 359-390 . Available at https://doi.org/10.1152/jn.1944.7.6.359
    CrossrefPubMedGoogle Scholar
  • 138 Hadjikhani N, Sanchez Del Rio M, Wu O. et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A 2001; 98 (08) 4687-4692
    CrossrefPubMedGoogle Scholar
  • 139 Santos E, Schöll M, Sánchez-Porras R. et al. Radial, spiral and reverberating waves of spreading depolarization occur in the gyrencephalic brain. Neuroimage 2014; 99: 244-255
    CrossrefPubMedGoogle Scholar
  • 140 Santos E, Sánchez-Porras R, Sakowitz OW, Dreier JP, Dahlem MA. Heterogeneous propagation of spreading depolarizations in the lissencephalic and gyrencephalic brain. J Cereb Blood Flow Metab 2017; 37 (07) 2639-2643
    CrossrefPubMedGoogle Scholar
  • 141 Harriott AM, Takizawa T, Chung DY, Chen SP. Spreading depression as a preclinical model of migraine. J Headache Pain 2019; 20 (01) 45
    CrossrefPubMedGoogle Scholar
  • 142 Ayata C, Lauritzen M. Spreading depression, spreading depolarizations, and the cerebral vasculature. Physiol Rev 2015; 95 (03) 953-993
    CrossrefPubMedGoogle Scholar
  • 143 Fabricius M, Jensen LH, Lauritzen M. Microdialysis of interstitial amino acids during spreading depression and anoxic depolarization in rat neocortex. Brain Res 1993; 612 (1-2): 61-69
    CrossrefPubMedGoogle Scholar
  • 144 Parker PD, Suryavanshi P, Melone M. et al. Non-canonical glutamate signaling in a genetic model of migraine with aura. Neuron 2021; 109 (04) 611-628.e8
    CrossrefPubMedGoogle Scholar
  • 145 Schain AJ, Melo-Carrillo A, Strassman AM, Burstein R. Cortical spreading depression closes paravascular space and impairs glymphatic flow: implications for migraine headache. J Neurosci 2017; 37 (11) 2904-2915
    CrossrefPubMedGoogle Scholar
  • 146 Peters O, Schipke CG, Hashimoto Y, Kettenmann H. Different mechanisms promote astrocyte Ca2+ waves and spreading depression in the mouse neocortex. J Neurosci 2003; 23 (30) 9888-9896
    CrossrefPubMedGoogle Scholar
  • 147 Chuquet J, Hollender L, Nimchinsky EA. High-resolution in vivo imaging of the neurovascular unit during spreading depression. J Neurosci 2007; 27 (15) 4036-4044
    CrossrefPubMedGoogle Scholar
  • 148 Ayata C, Shin HK, Salomone S. et al. Pronounced hypoperfusion during spreading depression in mouse cortex. J Cereb Blood Flow Metab 2004; 24 (10) 1172-1182
    CrossrefPubMedGoogle Scholar
  • 149 Yuzawa I, Sakadžić S, Srinivasan VJ. et al. Cortical spreading depression impairs oxygen delivery and metabolism in mice. J Cereb Blood Flow Metab 2012; 32 (02) 376-386
    CrossrefPubMedGoogle Scholar
  • 150 Chang JC, Shook LL, Biag J. et al. Biphasic direct current shift, haemoglobin desaturation and neurovascular uncoupling in cortical spreading depression. Brain 2010; 133 (Pt 4): 996-1012
    CrossrefPubMedGoogle Scholar
  • 151 Read SJ, Smith MI, Hunter AJ, Parsons AA. The dynamics of nitric oxide release measured directly and in real time following repeated waves of cortical spreading depression in the anaesthetised cat. Neurosci Lett 1997; 232 (03) 127-130
    CrossrefPubMedGoogle Scholar
  • 152 Mutch WA, Hansen AJ. Extracellular pH changes during spreading depression and cerebral ischemia: mechanisms of brain pH regulation. J Cereb Blood Flow Metab 1984; 4 (01) 17-27
    CrossrefPubMedGoogle Scholar
  • 153 Schock SC, Munyao N, Yakubchyk Y. et al. Cortical spreading depression releases ATP into the extracellular space and purinergic receptor activation contributes to the induction of ischemic tolerance. Brain Res 2007; 1168: 129-138
    CrossrefPubMedGoogle Scholar
  • 154 Takizawa T, Qin T, Lopes de Morais A. et al. Non-invasively triggered spreading depolarizations induce a rapid pro-inflammatory response in cerebral cortex. J Cereb Blood Flow Metab 2020; 40 (05) 1117-1131
    CrossrefPubMedGoogle Scholar
  • 155 Kraig RP, Dong LM, Thisted R, Jaeger CB. Spreading depression increases immunohistochemical staining of glial fibrillary acidic protein. J Neurosci 1991; 11 (07) 2187-2198
    CrossrefPubMedGoogle Scholar
  • 156 Sukhotinsky I, Dilekoz E, Wang Y. et al. Chronic daily cortical spreading depressions suppress spreading depression susceptibility. Cephalalgia 2011; 31 (16) 1601-1608
    CrossrefPubMedGoogle Scholar
  • 157 Ghaemi A, Alizadeh L, Babaei S. et al. Astrocyte-mediated inflammation in cortical spreading depression. Cephalalgia 2018; 38 (04) 626-638
    CrossrefPubMedGoogle Scholar
  • 158 Chen SP, Qin T, Seidel JL. et al. Inhibition of the P2 × 7-PANX1 complex suppresses spreading depolarization and neuroinflammation. Brain 2017; 140 (06) 1643-1656
    CrossrefPubMedGoogle Scholar
  • 159 Karatas H, Erdener SE, Gursoy-Ozdemir Y. et al. Spreading depression triggers headache by activating neuronal Panx1 channels. Science 2013; 339 (6123): 1092-1095
    CrossrefPubMedGoogle Scholar
  • 160 Eikermann-Haerter K, Dileköz E, Kudo C. et al. Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1. J Clin Invest 2009; 119 (01) 99-109
    PubMedGoogle Scholar
  • 161 van den Maagdenberg AM, Pizzorusso T, Kaja S. et al. High cortical spreading depression susceptibility and migraine-associated symptoms in Ca(v)2.1 S218L mice. Ann Neurol 2010; 67 (01) 85-98
    CrossrefPubMedGoogle Scholar
  • 162 Leo L, Gherardini L, Barone V. et al. Increased susceptibility to cortical spreading depression in the mouse model of familial hemiplegic migraine type 2. PLoS Genet 2011; 7 (06) e1002129
    CrossrefPubMedGoogle Scholar
  • 163 Moskowitz MA, Nozaki K, Kraig RP. Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms. J Neurosci 1993; 13 (03) 1167-1177
    CrossrefPubMedGoogle Scholar
  • 164 Zhang X, Levy D, Noseda R, Kainz V, Jakubowski M, Burstein R. Activation of meningeal nociceptors by cortical spreading depression: implications for migraine with aura. J Neurosci 2010; 30 (26) 8807-8814
    CrossrefPubMedGoogle Scholar
  • 165 Zhang X, Levy D, Kainz V, Noseda R, Jakubowski M, Burstein R. Activation of central trigeminovascular neurons by cortical spreading depression. Ann Neurol 2011; 69 (05) 855-865
    CrossrefPubMedGoogle Scholar
  • 166 Melo-Carrillo A, Noseda R, Nir RR. et al. Selective inhibition of trigeminovascular neurons by fremanezumab: a humanized monoclonal anti-CGRP antibody. J Neurosci 2017; 37 (30) 7149-7163
    CrossrefPubMedGoogle Scholar
  • 167 Filiz A, Tepe N, Eftekhari S. et al. CGRP receptor antagonist MK-8825 attenuates cortical spreading depression induced pain behavior. Cephalalgia 2019; 39 (03) 354-365
    CrossrefPubMedGoogle Scholar
  • 168 Cottier KE, Galloway EA, Calabrese EC. et al. Loss of blood-brain barrier integrity in a KCl-induced model of episodic headache enhances CNS drug delivery. eNeuro 2018; 5 (04) ENEURO.0116 -18.2018
    CrossrefPubMedGoogle Scholar
  • 169 Tang C, Unekawa M, Kitagawa S. et al. Cortical spreading depolarisation-induced facial hyperalgesia, photophobia and hypomotility are ameliorated by sumatriptan and olcegepant. Sci Rep 2020; 10 (01) 11408
    CrossrefPubMedGoogle Scholar
  • 170 Harriott AM, Chung DY, Uner A. et al. Optogenetic spreading depression elicits trigeminal pain and anxiety behavior. Ann Neurol 2021; 89 (01) 99-110
    CrossrefPubMedGoogle Scholar
  • 171 Schwedt TJ, Chong CD, Chiang CC, Baxter L, Schlaggar BL, Dodick DW. Enhanced pain-induced activity of pain-processing regions in a case-control study of episodic migraine. Cephalalgia 2014; 34 (12) 947-958
    CrossrefPubMedGoogle Scholar
  • 172 Harriott AM, Schwedt TJ. Migraine is associated with altered processing of sensory stimuli. Curr Pain Headache Rep 2014; 18 (11) 458
    CrossrefPubMedGoogle Scholar
  • 173 Schwedt TJ, Schlaggar BL, Mar S. et al. Atypical resting-state functional connectivity of affective pain regions in chronic migraine. Headache 2013; 53 (05) 737-751
    CrossrefPubMedGoogle Scholar
  • 174 van der Kamp W, Maassen VanDenBrink A, Ferrari MD, van Dijk JG. Interictal cortical hyperexcitability in migraine patients demonstrated with transcranial magnetic stimulation. J Neurol Sci 1996; 139 (01) 106-110
    CrossrefPubMedGoogle Scholar
  • 175 van der Kamp W, MaassenVanDenBrink A, Ferrari MD, van Dijk JG. Interictal cortical excitability to magnetic stimulation in familial hemiplegic migraine. Neurology 1997; 48 (05) 1462-1464
    CrossrefPubMedGoogle Scholar
  • 176 Coppola G, Di Lorenzo C, Schoenen J, Pierelli F. Habituation and sensitization in primary headaches. J Headache Pain 2013; 14: 65
    CrossrefPubMedGoogle Scholar
  • 177 Wang W, Schoenen J. Interictal potentiation of passive “oddball” auditory event-related potentials in migraine. Cephalalgia 1998; 18 (05) 261-265 , discussion 241
    CrossrefPubMedGoogle Scholar
  • 178 Höffken O, Stude P, Lenz M, Bach M, Dinse HR, Tegenthoff M. Visual paired-pulse stimulation reveals enhanced visual cortex excitability in migraineurs. Eur J Neurosci 2009; 30 (04) 714-720
    CrossrefPubMedGoogle Scholar
  • 179 McAdams H, Kaiser EA, Igdalova A. et al. Selective amplification of ipRGC signals accounts for interictal photophobia in migraine. Proc Natl Acad Sci U S A 2020; 117 (29) 17320-17329
    CrossrefPubMedGoogle Scholar
  • 180 Noseda R, Kainz V, Jakubowski M. et al. A neural mechanism for exacerbation of headache by light. Nat Neurosci 2010; 13 (02) 239-245
    CrossrefPubMedGoogle Scholar
  • 181 Noseda R, Lee AJ, Nir RR. et al. Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine. Proc Natl Acad Sci U S A 2017; 114 (28) E5683-E5692
    CrossrefPubMedGoogle Scholar
  • 182 Sowers LP, Wang M, Rea BJ. et al. Stimulation of posterior thalamic nuclei induces photophobic behavior in mice. Headache 2020; 60 (09) 1961-1981
    CrossrefPubMedGoogle Scholar
  • 183 Möller M, May A. The unique role of the trigeminal autonomic reflex and its modulation in primary headache disorders. Curr Opin Neurol 2019; 32 (03) 438-442
    CrossrefPubMedGoogle Scholar
  • 184 Goadsby PJ. Pathophysiology of cluster headache: a trigeminal autonomic cephalgia. Lancet Neurol 2002; 1 (04) 251-257
    CrossrefPubMedGoogle Scholar
  • 185 Rozen TD, Fishman RS. Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden. Headache 2012; 52 (01) 99-113
    CrossrefPubMedGoogle Scholar
  • 186 Naber WC, Fronczek R, Haan J. et al. The biological clock in cluster headache: a review and hypothesis. Cephalalgia 2019; 39 (14) 1855-1866
    CrossrefPubMedGoogle Scholar
  • 187 May A, Bahra A, Büchel C, Frackowiak RS, Goadsby PJ. Hypothalamic activation in cluster headache attacks. Lancet 1998; 352 (9124): 275-278
    CrossrefPubMedGoogle Scholar
  • 188 Morelli N, Pesaresi I, Cafforio G. et al. Functional magnetic resonance imaging in episodic cluster headache. J Headache Pain 2009; 10 (01) 11-14
    CrossrefPubMedGoogle Scholar
  • 189 Qiu E, Tian L, Wang Y, Ma L, Yu S. Abnormal coactivation of the hypothalamus and salience network in patients with cluster headache. Neurology 2015; 84 (14) 1402-1408
    CrossrefPubMedGoogle Scholar
  • 190 Qiu E, Wang Y, Ma L. et al. Abnormal brain functional connectivity of the hypothalamus in cluster headaches. PLoS One 2013; 8 (02) e57896
    CrossrefPubMedGoogle Scholar
  • 191 Leone M, Lucini V, D'Amico D. et al. Abnormal 24-hour urinary excretory pattern of 6-sulphatoxymelatonin in both phases of cluster headache. Cephalalgia 1998; 18 (10) 664-667
    CrossrefPubMedGoogle Scholar
  • 192 Polleri A, Nappi G, Murialdo G, Bono G, Martignoni E, Savoldi F. Changes in the 24-hour prolactin pattern in cluster headache. Cephalalgia 1982; 2 (01) 1-7
    CrossrefPubMedGoogle Scholar
  • 193 Waldenlind E, Gustafsson SA, Ekbom K, Wetterberg L. Circadian secretion of cortisol and melatonin in cluster headache during active cluster periods and remission. J Neurol Neurosurg Psychiatry 1987; 50 (02) 207-213
    CrossrefPubMedGoogle Scholar
  • 194 Gormley P, Anttila V, Winsvold BS. et al; International Headache Genetics Consortium. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet 2016; 48 (08) 856-866
    CrossrefPubMedGoogle Scholar
  • 195 Vgontzas A, Renthal W. Migraine-associated gene expression in cell types of the central and peripheral nervous system. Cephalalgia 2020; 40 (05) 517-523
    CrossrefPubMedGoogle Scholar
  • 196 Hautakangas H, Winsvold BS, Ruotsalainen SE. et al; International Headache Genetics Consortium; HUNT All-in Headache; Danish Blood Donor Study Genomic Cohort. Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles. Nat Genet 2022; 54 (02) 152-160
    CrossrefPubMedGoogle Scholar
  • 197 O'Connor E, Fourier C, Ran C. et al. Genome-wide association study identifies risk loci for cluster headache. Ann Neurol 2021; 90 (02) 193-202
    CrossrefPubMedGoogle Scholar
  • 198 Messlinger K. The big CGRP flood - sources, sinks and signalling sites in the trigeminovascular system. J Headache Pain 2018; 19 (01) 22
    CrossrefPubMedGoogle Scholar
  • 199 Ghanizada H, Al-Karagholi MA, Arngrim N. et al. Effect of adrenomedullin on migraine-like attacks in patients with migraine: a randomized crossover study. Neurology 2021; 96 (20) e2488-e2499
    CrossrefPubMedGoogle Scholar
  • 200 Shelukhina I, Mikhailov N, Abushik P, Nurullin L, Nikolsky EE, Giniatullin R. Cholinergic nociceptive mechanisms in rat meninges and trigeminal ganglia: potential implications for migraine pain. Front Neurol 2017; 8: 163
    CrossrefPubMedGoogle Scholar
  • 201 Dussor G, Yan J, Xie JY, Ossipov MH, Dodick DW, Porreca F. Targeting TRP channels for novel migraine therapeutics. ACS Chem Neurosci 2014; 5 (11) 1085-1096
    CrossrefPubMedGoogle Scholar
  • 202 Krivoshein G, Tolner EA, van den Maagdenberg AMJM, Giniatullin RA. Correction to: migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists. J Headache Pain 2022; 23 (01) 17
    CrossrefPubMedGoogle Scholar