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The Journal of Headache and Pain
Published in: The Journal of Headache and Pain 1/2020

01-12-2020 | Migraine | Review article

The fifth cranial nerve in headaches

Authors: J. C. A. Edvinsson, A. Viganò, A. Alekseeva, E. Alieva, R. Arruda, C. De Luca, N. D’Ettore, I. Frattale, M. Kurnukhina, N. Macerola, E. Malenkova, M. Maiorova, A. Novikova, P. Řehulka, V. Rapaccini, O. Roshchina, G. Vanderschueren, L. Zvaune, A. P. Andreou, K. A. Haanes, On behalf of the European Headache Federation School of Advanced Studies (EHF-SAS)

Published in: The Journal of Headache and Pain | Issue 1/2020

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Abstract

The fifth cranial nerve is the common denominator for many headaches and facial pain pathologies currently known. Projecting from the trigeminal ganglion, in a bipolar manner, it connects to the brainstem and supplies various parts of the head and face with sensory innervation. In this review, we describe the neuroanatomical structures and pathways implicated in the sensation of the trigeminal system. Furthermore, we present the current understanding of several primary headaches, painful neuropathies and their pharmacological treatments. We hope that this overview can elucidate the complex field of headache pathologies, and their link to the trigeminal nerve, to a broader field of young scientists.
Literature
1.
(2018) Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38(1):1–211
2.
Ray BS, Wolff HG (1940) Experimental studies on headache: pain-sensitive structures of the head and their significance in headache. Arch Surg 41(4):813–856CrossRef
3.
Silberstein SD, Lipton RB, Dalessio DJ (2001) Wolff's headache and other head pain: Oxford University press
4.
Fontaine D, Almairac F, Santucci S, Fernandez C, Dallel R, Pallud J et al (2018) Dural and pial pain-sensitive structures in humans: new inputs from awake craniotomies. Brain 141(4):1040–1048PubMedCrossRef
5.
Edvinsson L (2011) Tracing neural connections to pain pathways with relevance to primary headaches. Cephalalgia 31(6):737–747PubMedCrossRef
6.
Stovner LJ, Nichols E, Steiner TJ, Abd-Allah F, Abdelalim A, Al-Raddadi RM et al (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 Neurology 17(11):954–976CrossRef
7.
(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 Neurology 17(11):954–976
8.
James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N et al (2018) Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the global burden of disease study 2017. Lancet 392(10159):1789–1858CrossRef
9.
Linde M, Gustavsson A, Stovner LJ, Steiner TJ, Barré J, Katsarava Z et al (2012) The cost of headache disorders in Europe: the Eurolight project. Eur J Neurol 19(5):703–711PubMedCrossRef
10.
Feigin VL, et al. (2020) The global burden of neurological disorders: translating evidence into policy Lancet Neurol 19(3):255-265
11.
Finnerup NB, Nikolajsen L, Jensen TS (2012) Are we neglecting spinal reorganization following nerve damage? Pain 153(2):269–272PubMedCrossRef
12.
Frederiksen SD, Haanes KA, Warfvinge K, Edvinsson L (2019) Perivascular neurotransmitters: regulation of cerebral blood flow and role in primary headaches. J Cereb Blood Flow Metab 39(4):610–632PubMedCrossRef
13.
Edvinsson L, Krause D. Cerebral Blood Flow and Metabolism (2002). Philadelphia: Lippincott Williams & Wilkins 17(521):8
14.
Edvinsson L (2017) The Trigeminovascular pathway: role of CGRP and CGRP receptors in migraine. Headache 57(Suppl 2):47–55PubMedCrossRef
15.
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:S44–S53PubMedCrossRef
16.
Eftekhari S, Salvatore CA, Johansson S, Chen TB, Zeng Z, Edvinsson L (2015) Localization of CGRP, CGRP receptor, PACAP and glutamate in trigeminal ganglion Relation to the blood-brain barrier. Brain Res 1600:93–109PubMedCrossRef
17.
Messlinger K, Russo AF (2019) Current understanding of trigeminal ganglion structure and function in headache. Cephalalgia 39(13):1661–1674PubMedCrossRef
18.
Thalakoti S, Patil VV, Damodaram S, Vause CV, Langford LE, Freeman SE et al (2007) Neuron–glia signaling in trigeminal ganglion: implications for migraine pathology. Headache 47(7):1008–1023PubMedPubMedCentralCrossRef
19.
20.
21.
Bista P, Wendy L (2019) Imlach. "Pathological Mechanisms and Therapeutic Targets for Trigeminal Neuropathic Pain." Medicines 6(3):91
22.
Pennisi E, Cruccu G, Manfredi M, Palladini G (1991) Histometric study of myelinated fibers in the human trigeminal nerve. J Neurol Sci 105(1):22–28PubMedCrossRef
23.
Jay GW, Barkin RL (2017) Primary headache disorders- part 2: tension-type headache and medication overuse headache. Dis Mon 63(12):342–367PubMedCrossRef
24.
Bendtsen L (2003) Central and peripheral sensitization in tension-type headache. Curr Pain Headache Rep 7(6):460–465PubMedCrossRef
25.
Fumal A, Schoenen J (2008) Tension-type headache: current research and clinical management. Lancet Neurology. 7(1):70–83PubMedCrossRef
26.
Rusu MC, Cretoiu D, Vrapciu AD, Hostiuc S, Dermengiu D, Manoiu VS et al (2016) Telocytes of the human adult trigeminal ganglion. Cell Biol Toxicol 32(3):199–207PubMedCrossRef
27.
De Luca C, Colangelo AM, Alberghina L, Papa M (2018) Neuro-immune hemostasis: homeostasis and diseases in the central nervous system. Front Cell Neurosci 12:459PubMedPubMedCentralCrossRef
28.
29.
Edvinsson L, Haanes KA, Warfvinge K, Krause DN (2018) CGRP as the target of new migraine therapies — successful translation from bench to clinic. Nat Rev Neurol 14(6):338–350PubMedCrossRef
30.
Lundblad C, Haanes KA, Grande G, Edvinsson L (2015) Expeerimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage. J Headache Pain 16:91PubMedPubMedCentralCrossRef
31.
De Luca C, Savarese L, Colangelo AM, Bianco MR, Cirillo G, Alberghina L et al (2016) Astrocytes and microglia-mediated immune response in maladaptive plasticity is differently modulated by NGF in the ventral horn of the spinal cord following peripheral nerve injury. Cell Mol Neurobiol 36(1):37–46PubMedCrossRef
32.
Cirillo G, Colangelo AM, Berbenni M, Ippolito VM, De Luca C, Verdesca F et al (2015) Purinergic modulation of spinal neuroglial maladaptive plasticity following peripheral nerve injury. Mol Neurobiol 52(3):1440–1457PubMedCrossRef
33.
Papa M, De Luca C, Petta F, Alberghina L, Cirillo G (2014) Astrocyte-neuron interplay in maladaptive plasticity. Neurosci Biobehav Rev 42:35–54PubMedCrossRef
34.
Virtuoso A, Herrera-Rincon C, Papa M, Panetsos F (2019) Dependence of Neuroprosthetic stimulation on the sensory modality of the trigeminal neurons following nerve injury. Implications in the Design of Future Sensory Neuroprostheses for correct perception and modulation of neuropathic pain. Front Neurosci 13:389PubMedPubMedCentralCrossRef
35.
Takeda M, Takahashi M, Nasu M, Matsumoto S (2011) Peripheral inflammation suppresses inward rectifying potassium currents of satellite glial cells in the trigeminal ganglia. Pain 152(9):2147–2156PubMedCrossRef
36.
37.
Kawaguchi A, Sato M, Kimura M, Ichinohe T, Tazaki M, Shibukawa Y (2015) Expression and function of purinergic P2Y12 receptors in rat trigeminal ganglion neurons. Neurosci Res 98:17–27PubMedCrossRef
38.
Goto T, Oh SB, Takeda M, Shinoda M, Sato T, Gunjikake KK et al (2016) Recent advances in basic research on the trigeminal ganglion. J Physiol Sci 66(5):381–386PubMedCrossRef
39.
Haanes KA, Edvinsson L (2014) Expression and characterization of purinergic receptors in rat middle meningeal artery-potential role in migraine. PLoS One 9(9):e108782PubMedPubMedCentralCrossRef
40.
Haanes KA, Labastida-Ramírez A, Blixt FW, Rubio-Beltrán E, Dirven CM, Danser AH et al (2019) Exploration of purinergic receptors as potential anti-migraine targets using established pre-clinical migraine models. Cephalalgia 39(11):1421–1434PubMedCrossRef
41.
Gates P (2006) Duus’ topical diagnosis in neurology: anatomy, physiology, signs, symptoms, −by M. Baehr and M. Frotscher. Int Med J 36(9):557CrossRef
42.
Toshida H, Suto C (2018) Preganglionic parasympathetic denervation rabbit model for innervation studies. Cornea 37(Suppl 1):S106–Ss12PubMedCrossRef
43.
Morgan C, DeGroat WC, Jannetta PJ (1987) Sympathetic innervation of the cornea from the superior cervical ganglion. An HRP study in the cat. J Auton Nerv Syst 20(2):179–183PubMedCrossRef
44.
Suzuki N, Hardebo JE, Owman C (1989) Trigeminal fibre collaterals storing substance P and calcitonin gene-related peptide associate with ganglion cells containing choline acetyltransferase and vasoactive intestinal polypeptide in the sphenopalatine ganglion of the rat. An axon reflex modulating parasympathetic ganglionic activity? Neuroscience 30(3):595–604PubMedCrossRef
45.
Larrier D, Lee A (2003) Anatomy of headache and facial pain. Otolaryngol Clin N Am 36(6):1041–1053 vCrossRef
46.
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):553–622PubMedPubMedCentralCrossRef
47.
Liu-Chen LY, Han DH, Moskowitz MA (1983) Pia arachnoid contains substance P originating from trigeminal neurons. Neuroscience 9(4):803–808PubMedCrossRef
48.
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(1):162–166PubMedCrossRef
49.
Mayberg MR, 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(1):46–56PubMedCrossRef
50.
Penfield W, McNAUGHTON F (1940) Dural headache and innervation of the dura mater. Arch Neurol Psychiatr 44(1):43–75CrossRef
51.
Anastasi G, Capitani S, Carnazza M, Cinti S, Cremona O, De Caro R, et al. (2010) Trattato di anatomia umana
52.
53.
Donnet A, Simon E, Cuny E, Demarquay G, Ducros A, De Gaalon S et al (2017) French guidelines for diagnosis and treatment of classical trigeminal neuralgia (French headache society and French neurosurgical society). Rev Neurol (Paris) 173(3):131–151CrossRef
54.
Brazis PW, Masdeu JC (2011) Localization in Clinical Neurology (sixth ed.), Philadelphia: Lippincott Williams & Wilkins
55.
Piovesan EJ, Kowacs PA, Oshinsky ML (2003) Convergence of cervical and trigeminal sensory afferents. Curr Pain Headache Rep 7(5):377–383PubMedCrossRef
56.
Haines DE, Mihailoff GA (2017) Fundamental neuroscience for Basic and clinical applications E-book: Elsevier health sciences
57.
Fisch A (2012) Neuroanatomy: draw it to know it: OUP USA
58.
Rusu MC (2004) The spinal trigeminal nucleus-considerations on the structure of the nucleus caudalis. Folia Morphol (Warsz) 63(3):325–328
59.
Pradier B, McCormick SJ, Tsuda AC, Chen RW, Atkinson AL, Westrick MR et al (2019) Properties of neurons in the superficial laminae of trigeminal nucleus caudalis. Physiol Rep 7(12):e14112PubMedPubMedCentralCrossRef
60.
Noseda R, Jakubowski M, Kainz V, Borsook D, Burstein R (2011) Cortical projections of functionally identified thalamic trigeminovascular neurons: implications for migraine headache and its associated symptoms. J Neurosci 31(40):14204–14217PubMedPubMedCentralCrossRef
61.
Malick A, Strassman RM, Burstein R (2000) Trigeminohypothalamic and reticulohypothalamic tract neurons in the upper cervical spinal cord and caudal medulla of the rat. J Neurophysiol 84(4):2078–2112PubMedCrossRef
62.
Almeida TF, Roizenblatt S, Tufik S (2004) Afferent pain pathways: a neuroanatomical review. Brain Res 1000(1–2):40–56PubMedCrossRef
63.
Patel NM, Das JM (2019) Neuroanatomy, Spinal Trigeminal Nucleus. StatPearls Publishing, StatPearls
64.
Kocorowski LH, Helmstetter FJ (2001) Calcitonin gene-related peptide released within the amygdala is involved in Pavlovian auditory fear conditioning. Neurobiol Learn Mem 75(2):149–163PubMedCrossRef
65.
66.
Han JS, Li W, Neugebauer V (2005) Critical role of calcitonin gene-related peptide 1 receptors in the amygdala in synaptic plasticity and pain behavior. J Neurosci 25(46):10717–10728PubMedPubMedCentralCrossRef
67.
Shinohara K, Watabe AM, Nagase M, Okutsu Y, Takahashi Y, Kurihara H et al (2017) Essential role of endogenous calcitonin gene-related peptide in pain-associated plasticity in the central amygdala. Eur J Neurosci 46(6):2149–2160PubMedPubMedCentralCrossRef
68.
Missig G, Mei L, Vizzard MA, Braas KM, Waschek JA, Ressler KJ et al (2017) Parabrachial pituitary adenylate cyclase-activating polypeptide activation of amygdala endosomal extracellular signal–regulated kinase signaling regulates the emotional component of pain. Biol Psychiatry 81(8):671–682PubMedCrossRef
69.
Sohn JH, Choi HC, Kim CH (2013) Differences between episodic and chronic tension-type headaches in nociceptive-specific trigeminal pathways. Cephalalgia 33(5):330–339PubMedCrossRef
70.
Schwartz BS, Stewart WF, Simon D, Lipton RB (1998) Epidemiology of tension-type headache. Jama 279(5):381–383PubMedCrossRef
71.
Bendtsen L (2000) Central sensitization in tension-type headache--possible pathophysiological mechanisms. Cephalalgia 20(5):486–508PubMedCrossRef
72.
73.
Goadsby PJ (2009) The vascular theory of migraine--a great story wrecked by the facts. Brain 132(Pt 1):6–7PubMedCrossRef
74.
Amin FM, Asghar MS, Hougaard A, Hansen AE, Larsen VA, de Koning PJ et al (2013) Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study. Lancet Neurology 12(5):454–461PubMedCrossRef
75.
Charles A (2013) Vasodilation out of the picture as a cause of migraine headache. Lancet Neurology 12(5):419–420PubMedCrossRef
76.
Goadsby P, Edvinsson L, Ekman R (1988) Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol 23(2):193–196PubMedCrossRef
77.
Tuka B, Helyes Z, Markovics A, Bagoly T, Németh J, Márk L et al (2012) Peripheral and central alterations of pituitary adenylate cyclase activating polypeptide-like immunoreactivity in the rat in response to activation of the trigeminovascular system. Peptides 33(2):307–316PubMedCrossRef
78.
Lassen L, Haderslev P, Jacobsen V, Iversen HK, Sperling B, Olesen J (2002) CGRP may play a causative role in migraine. Cephalalgia 22(1):54–61PubMedCrossRef
79.
Olesen J, Burstein R, Ashina M, Tfelt-Hansen P (2009) Origin of pain in migraine: evidence for peripheral sensitisation. Lancet Neurology 8(7):679–690PubMedCrossRef
80.
Hou M, Uddman R, Tajti J, Kanje M, Edvinsson L (2002) Capsaicin receptor immunoreactivity in the human trigeminal ganglion. Neurosci Lett 330(3):223–226PubMedCrossRef
81.
82.
83.
Vigano A, Manica A, Di Piero V, Leonardi M (2019) Did going north give us migraine? An evolutionary approach on understanding latitudinal differences in migraine epidemiology. Headache 59(4):632–634PubMedPubMedCentralCrossRef
84.
Malick A, Burstein R (2000) Peripheral and central sensitization during migraine. Funct Neurol 15:28–35PubMed
85.
Aurora SK, Brin MF (2017) Chronic migraine: an update on physiology, imaging, and the mechanism of action of two available pharmacologic therapies. Headache 57(1):109–125PubMedCrossRef
86.
Moskowitz MA (2008) Defining a pathway to discovery from bench to bedside: the trigeminovascular system and sensitization. Headache 48(5):688–690PubMedCrossRef
87.
Burstein R, Jakubowski M, Garcia-Nicas E, Kainz V, Bajwa Z, Hargreaves R et al (2010) Thalamic sensitization transforms localized pain into widespread allodynia. Ann Neurol 68(1):81–91PubMedPubMedCentralCrossRef
88.
Cernuda-Morollón E, Larrosa D, Ramón C, Vega J, Martínez-Camblor P, Pascual J (2013) Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology 81(14):1191–1196PubMedCrossRef
89.
Edvinsson L, Haanes KA, Warfvinge K (2019) Does inflammation have a role in migraine? Nat Rev Neurol 15(8):483–490PubMedCrossRef
90.
Goadsby P, Edvinsson L, Ekman R (1990) Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurology 28(2):183–187CrossRef
91.
Lukács M, Haanes KA, Majláth Z, Tajti J, Vécsei L, Warfvinge K et al (2015) Dural administration of inflammatory soup or complete Freund’s adjuvant induces activation and inflammatory response in the rat trigeminal ganglion. J Headache Pain 16(1):79PubMedCentralCrossRef
92.
Fernandez-de-las-Penas C, Cuadrado ML, Arendt-Nielsen L, Simons DG, Pareja JA (2007) Myofascial trigger points and sensitization: an updated pain model for tension-type headache. Cephalalgia 27(5):383–393PubMedCrossRef
93.
94.
95.
Perrotta A, Serrao M, Sandrini G, Bogdanova D, Tassorelli C, Bartolo M et al (2008) Reduced habituation of trigeminal reflexes in patients with episodic cluster headache during cluster period. Cephalalgia 28(9):950–959PubMedCrossRef
96.
Lee J, Lin RL, Garcia RG, Kim J, Kim H, Loggia ML et al (2017) Reduced insula habituation associated with amplification of trigeminal brainstem input in migraine. Cephalalgia 37(11):1026–1038PubMedCrossRef
97.
Diener HC, Dodick D, Evers S, Holle D, Jensen RH, Lipton RB et al (2019) Pathophysiology, prevention, and treatment of medication overuse headache. Lancet Neurology 18(9):891–902PubMedCrossRef
98.
Diener HC, Holle D, Solbach K, Gaul C (2016) Medication-overuse headache: risk factors, pathophysiology and management. Nat Rev Neurol 12(10):575–583PubMedCrossRef
99.
Supornsilpchai W, le Grand SM, Srikiatkhachorn A (2010) Cortical hyperexcitability and mechanism of medication-overuse headache. Cephalalgia 30(9):1101–1109PubMedCrossRef
100.
Okada-Ogawa A, Porreca F, Meng ID (2009) Sustained morphine-induced sensitization and loss of diffuse noxious inhibitory controls in dura-sensitive medullary dorsal horn neurons. J Neurosci 29(50):15828–15835PubMedPubMedCentralCrossRef
101.
Srikiatkhachorn A, Anthony M (1996) Platelet serotonin in patients with analgesic-induced headache. Cephalalgia 16(6):423–426PubMedCrossRef
102.
Coppola G, Currà A, Di Lorenzo C, Parisi V, Gorini M, Sava SL et al (2010) Abnormal cortical responses to somatosensory stimulation in medication-overuse headache. BMC Neurol 10(1):126PubMedPubMedCentralCrossRef
103.
Viganò A, Torrieri MC, Toscano M, Puledda F, Petolicchio B, D’Elia TS et al (2018) Neurophysiological correlates of clinical improvement after greater occipital nerve (GON) block in chronic migraine: relevance for chronic migraine pathophysiology. J Headache Pain 19(1):73PubMedPubMedCentralCrossRef
104.
Wei DY-T, Ong JJY, Goadsby PJ (2018) Overview of trigeminal autonomic cephalalgias: Nosologic evolution, diagnosis, and management. Ann Indian Acad Neurol 21(Suppl 1):S39PubMedPubMedCentral
105.
Tuka B, Szabó N, Tóth E, Kincses ZT, Párdutz Á, Szok D et al (2016) Release of PACAP-38 in episodic cluster headache patients–an exploratory study. J Headache Pain 17(1):69PubMedPubMedCentralCrossRef
106.
Goadsby PJ, Edvinsson L (1994) Human in vivo evidence for trigeminovascular activation in cluster headache neuropeptide changes and effects of acute attacks therapies. Brain 117(3):427–434PubMedCrossRef
107.
Goadsby PJ, Dodick DW, Leone M, Bardos JN, Oakes TM, Millen BA et al (2019) Trial of Galcanezumab in prevention of episodic cluster headache. N Engl J Med 381(2):132–141CrossRefPubMed
108.
109.
May A, Schwedt TJ, Magis D, Pozo-Rosich P, Evers S, Wang S-J (2018) Cluster headache. Nat Reviews Dis Prime 4:18006CrossRef
110.
Akerman S, Holland PR, Summ O, Lasalandra MP, Goadsby PJ (2012) A translational in vivo model of trigeminal autonomic cephalalgias: therapeutic characterization. Brain 135(12):3664–3675PubMedCrossRef
111.
Schoenen J, Jensen RH, Lanteri-Minet M, Láinez MJ, Gaul C, Goodman AM et al (2013) Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia 33(10):816–830PubMedPubMedCentralCrossRef
112.
Cohen A (2017) SUN: short-lasting unilateral neuralgiform headache attacks. Headache 57(6):1010–1020PubMedCrossRef
113.
Pedersen JL, Barloese M, Jensen RH (2013) Neurostimulation in cluster headache: a review of current progress. Cephalalgia 33(14):1179–1193PubMedCrossRef
114.
Snoer A, Lund N, Beske R, Hagedorn A, Jensen RH, Barloese M (2018) Cluster headache beyond the pain phase: a prospective study of 500 attacks. Neurology 91(9):e822–ee31PubMedCrossRef
115.
Merskey HE (1986) Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. Pain 3:S1-226
116.
Maarbjerg S, Di Stefano G, Bendtsen L, Cruccu G (2017) Trigeminal neuralgia–diagnosis and treatment. Cephalalgia 37(7):648–657PubMedCrossRef
117.
118.
Huang C, Amasanti M, Lovell B, Young T (2017) Recurrent painful ophthalmoplegic neuropathy. Pract Neurol 17(4):318–320PubMedCrossRef
119.
120.
Pareja JA, Lopez-Ruiz P, Mayo D, Villar-Quiles RN, Carcamo A, Gutierrez-Viedma A et al (2017) Supratrochlear neuralgia: a prospective case series of 15 patients. Headache 57(9):1433–1442PubMedCrossRef
121.
Pareja JA, Cuadrado ML (2013) Lacrimal neuralgia: so far, a missing cranial neuralgia. Cephalalgia 33(14):1198–1202PubMedCrossRef
122.
123.
Pareja JA, Cuadrado ML, Porta-Etessam J, Fernandez-de-las-Penas C, Gili P, Caminero AB et al (2010) Idiopathic ophthalmodynia and idiopathic rhinalgia: two topographic facial pain syndromes. Headache 50(8):1286–1295PubMedCrossRef
124.
125.
Caldarelli C, Benech R, Iaquinta C (2016) Superior orbital fissure syndrome in lateral Orbital Wall fracture: management and classification update. Craniomaxillofac Trauma Reconstr 9(4):277–283PubMedPubMedCentralCrossRef
126.
Bendtsen L, Zakrzewska JM, Abbott J, Braschinsky M, Di Stefano G, Donnet A et al (2019) European academy of neurology guideline on trigeminal neuralgia. Eur J Neurol 26(6):831–849PubMedCrossRef
127.
Maarbjerg S, Gozalov A, Olesen J, Bendtsen L (2014) Trigeminal neuralgia–a prospective systematic study of clinical characteristics in 158 patients. Headache 54(10):1574–1582PubMedCrossRef
128.
Maarbjerg S, Wolfram F, Gozalov A, Olesen J, Bendtsen L (2015) Significance of neurovascular contact in classical trigeminal neuralgia. Brain 138(2):311–319PubMedCrossRef
129.
Obermann M, Rodriguez-Raecke R, Naegel S, Holle D, Mueller D, Yoon M-S et al (2013) Gray matter volume reduction reflects chronic pain in trigeminal neuralgia. Neuroimage 74:352–358PubMedCrossRef
130.
Tian T, Guo L, Xu J, Zhang S, Shi J, Liu C et al (2016) Brain white matter plasticity and functional reorganization underlying the central pathogenesis of trigeminal neuralgia. Sci Rep 6:36030PubMedPubMedCentralCrossRef
131.
Leal PRL, Barbier C, Hermier M, Souza MA, Cristino-Filho G, Sindou M (2014) Atrophic changes in the trigeminal nerves of patients with trigeminal neuralgia due to neurovascular compression and their association with the severity of compression and clinical outcomes. J Neurosurg 120(6):1484–1495PubMedCrossRef
132.
133.
Forssell H, Tenovuo O, Silvoniemi P, Jaaskelainen SK (2007) Differences and similarities between atypical facial pain and trigeminal neuropathic pain. Neurology 69(14):1451–1459PubMedCrossRef
134.
Lang E, Kaltenhauser M, Seidler S, Mattenklodt P, Neundorfer B (2005) Persistent idiopathic facial pain exists independent of somatosensory input from the painful region: findings from quantitative sensory functions and somatotopy of the primary somatosensory cortex. Pain 118(1–2):80–91PubMedCrossRef
135.
Du B, Xu J, Hu J, Zhong X, Liang J, Lei P et al (2019) A clinical study of the intra-Neuroendoscopic technique for the treatment of subacute-chronic and chronic septal subdural hematoma. Front Neurol 10:1408PubMedCrossRef
136.
Moazzam AA, Habibian M (2012) Patients appearing to dental professionals with orofacial pain arising from intracranial tumors: a literature review. Oral Surg Oral Med Oral Pathol Oral Radiol 114(6):749–755PubMedCrossRef
137.
List T, Leijon G, Svensson P (2008) Somatosensory abnormalities in atypical odontalgia: a case-control study. Pain 139(2):333–341PubMedCrossRef
138.
Klasser GD, Grushka M, Su N (2016) Burning mouth syndrome. Oral Maxillofac Surg Clin North Am 28(3):381–396PubMedCrossRef
139.
Campbell WW Jr (1986) The numb cheek syndrome: a sign of infraorbital neuropathy. Neurology. 36(3):421–423PubMedCrossRef
140.
Lopez Mesonero L, Pedraza Hueso MI, Herrero Velazquez S, Guerrero Peral AL (2014) Infraorbital neuralgia: a diagnostic possibility in patients with zygomatic arch pain. Neurologia 29(6):381–382PubMedCrossRef
141.
Okholm C, Frendo M, Kiss K, von Buchwald C (2018) Cheek numbness caused by Perineural tumor invasion of the infraorbital nerve: a review of 3 diagnostically challenging cases. Am J Case Rep 19:296–300PubMedPubMedCentralCrossRef
142.
Cesarik M, Zavoreo I, Zadro-Matovina L, Papic M, Basic KV (2016) Effects of trigeminal nerve dysfunction in various types of headaches. Coll Antropol 40(3):183–188PubMed
143.
144.
Antony AB, Mazzola AJ, Dhaliwal GS, Hunter CW (2019) Neurostimulation for the treatment of chronic head and facial pain: a literature review. Pain Physician 22(5):447–477PubMed
145.
Hascalovici JR, Robbins MS (2017) Peripheral nerve blocks for the treatment of headache in older adults: a retrospective study. Headache 57(1):80–86PubMedCrossRef
146.
Coculescu EC, Radu A, Coculescu BI (2014) Burning mouth syndrome: a review on diagnosis and treatment. J Med Life 7(4):512–515PubMedPubMedCentral
147.
Aryeh HB, Gottlieb I, Ish-Shalom S, David A, Szargel H, Laufer D (1996) Oral complaints related to menopause. Maturitas 24(3):185–189PubMedCrossRef
148.
Klasser GD, Fischer DJ, Epstein JB (2008) Burning mouth syndrome: recognition, understanding, and management. Oral Maxillofac Surg Clin North Am 20(2):255–271 viiPubMedCrossRef
149.
Lauria G, Majorana A, Borgna M, Lombardi R, Penza P, Padovani A et al (2005) Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome. Pain. 115(3):332–337PubMedCrossRef
150.
151.
Heckmann SM, Kirchner E, Grushka M, Wichmann MG, Hummel T (2012) A double-blind study on clonazepam in patients with burning mouth syndrome. Laryngoscope 122(4):813–816PubMedCrossRef
152.
Cui Y, Xu H, Chen F, Liu J, Jiang L, Zhou Y et al (2016) Efficacy evaluation of clonazepam for symptom remission in burning mouth syndrome: a meta-analysis. Oral Dis 22(6):503–511PubMedCrossRef
153.
154.
Murphy MK, MacBarb RF, Wong ME, Athanasiou KA (2013) Temporomandibular disorders: a review of etiology, clinical management, and tissue engineering strategies. Int J Oral Maxillofac Implants 28(6):e393–e414PubMedPubMedCentralCrossRef
155.
Pihut M, Szuta M, Ferendiuk E, Zenczak-Wieckiewicz D (2014) Differential diagnostics of pain in the course of trigeminal neuralgia and temporomandibular joint dysfunction. Biomed Res Int 2014:563786PubMedPubMedCentral
156.
Haanes KA, Edvinsson L (2019) Pathophysiological mechanisms in migraine and the identification of new therapeutic targets. CNS Drugs 33(6):525–537PubMedCrossRef
157.
158.
Khoury CK, Couch JR (2010) Sumatriptan–naproxen fixed combination for acute treatment of migraine: a critical appraisal. Drug Des Dev Ther 4:9CrossRef
159.
Baraldi C, Pellesi L, Guerzoni S, Cainazzo MM, Pini LA (2017) Therapeutical approaches to paroxysmal hemicrania, hemicrania continua and short lasting unilateral neuralgiform headache attacks: a critical appraisal. J Headache Pain 18(1):71PubMedPubMedCentralCrossRef
160.
Sjaastad O (2006) Chronic paroxysmal hemicrania: from the index patient to the disease. Curr Pain Headache Rep 10(4):295–301PubMedCrossRef
161.
Neeb L, Hellen P, Boehnke C, Hoffmann J, Schuh-Hofer S, Dirnagl U et al (2011) IL-1β stimulates COX-2 dependent PGE2 synthesis and CGRP release in rat trigeminal ganglia cells. PLoS One 6(3):e17360PubMedPubMedCentralCrossRef
162.
Summ O, Evers S (2013) Mechanism of action of indomethacin in indomethacin-responsive headaches. Curr Pain Headache Rep 17(4):327PubMedCrossRef
163.
Summ O, Andreou AP, Akerman S, Goadsby PJ (2010) A potential nitrergic mechanism of action for indomethacin, but not of other COX inhibitors: relevance to indomethacin-sensitive headaches. J Headache Pain 11(6):477–483PubMedPubMedCentralCrossRef
164.
165.
Akerman S, Holland PR, Summ O, Lasalandra MP, Goadsby PJ (2012) A translational in vivo model of trigeminal autonomic cephalalgias: therapeutic characterization. Brain 135(Pt 12):3664–3675PubMedCrossRef
166.
Edvinsson L, Villalón CM, MaassenVanDenBrink A (2012) Basic mechanisms of migraine and its acute treatment. Pharmacol Ther 136(3):319–333PubMedCrossRef
167.
Edvinsson JCA, Warfvinge K, Krause DN, Blixt FW, Sheykhzade M, Edvinsson L et al (2019) C-fibers may modulate adjacent Adelta-fibers through axon-axon CGRP signaling at nodes of Ranvier in the trigeminal system. J Headache Pain 20(1):105PubMedPubMedCentralCrossRef
168.
Arvieu L, Mauborgne A, Bourgoin S, Oliver C, Feltz P, Hamon M et al (1996) Sumatriptan inhibits the release of CGRP and substance P from the rat spinal cord. Neuroreport 7(12):1973–1976PubMedCrossRef
169.
Silberstein SD, McCrory DC (2003) Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. Headache 43(2):144–166PubMedCrossRef
170.
Rubio-Beltrán E, Labastida-Ramírez A, Villalón CM, MaassenVanDenBrink A (2018) Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther 186:88–97PubMedCrossRef
171.
Kröger IL, May A (2015) Triptan-induced disruption of trigemino-cortical connectivity. Neurology 84(21):2124–2131PubMedCrossRef
172.
173.
Moore D, et al (2019) "A systematic review of rescue analgesic strategies in acute exacerbations of primary trigeminal neuralgia." Br J Anaesth 123.2:e385-e396
174.
175.
176.
Curto M, Cipolla F, Cisale GY, Capi M, Spuntarelli V, Guglielmetti M et al (2020) Profiling lasmiditan as a treatment option for migraine. Expert Opin Pharmacother 21(2):147-153.
177.
Walker CS, Raddant AC, Woolley MJ, Russo AF, Hay DL (2018) CGRP receptor antagonist activity of olcegepant depends on the signalling pathway measured. Cephalalgia 38(3):437–451PubMedCrossRef
178.
Scott LJ (2020) Ubrogepant: First Approval. Drugs 80(3):323-328.)
179.
Dach F, Éckeli ÁL, Ferreira KS, Speciali JG (2015) Nerve block for the treatment of headaches and cranial neuralgias–a practical approach. Headache 55:59–71PubMedCrossRef
180.
Bussone G, Rapoport A (2010) Acute and preventive treatment of cluster headache and other trigeminal autonomic cephalgias. Handbook Clin Neurol 97:431–442CrossRef
181.
Jürgens TP (2014) Therapie des trigeminoautonomen Kopfschmerzes. Bundesgesundheitsblatt-Gesundheitsforschung-Gesundheitsschutz. 57(8):983–995PubMedCrossRef
182.
183.
Linde M, Mulleners WM, Chronicle EP, McCrory DC (2013) Antiepileptics other than gabapentin, pregabalin, topiramate, and valproate for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev 6:CD010608.
184.
Suzuki-Muromoto S, Kosaki R, Kosaki K, Kubota M (2020) Familial hemiplegic migraine with a PRRT2 mutation: phenotypic variations and carbamazepine efficacy. Brain and Development 42(3):293–297PubMedCrossRef
185.
Parikh SK, Silberstein SD (2019) Current status of antiepileptic drugs as preventive migraine therapy. Curr Treat Options Neurol 21(4):16PubMedCrossRef
186.
Barbanti P, Egeo G, Mitsikostas DD (2019) Trigeminal-targeted treatments in migraine: is 60% the magic number? Headache 59(9):1659–1661PubMedCrossRef
187.
Deen M, Correnti E, Kamm K, Kelderman T, Papetti L, Rubio-Beltrán E et al (2017) Blocking CGRP in migraine patients–a review of pros and cons. J Headache 18(1):96CrossRef
188.
Melo-Carrillo A, Strassman AM, Nir R-R, Schain AJ, Noseda R, Stratton J et al (2017) Fremanezumab—a humanized monoclonal anti-CGRP antibody—inhibits thinly myelinated (Aδ) but not unmyelinated (C) meningeal nociceptors. J Neurosci 37(44):10587–10596PubMedPubMedCentralCrossRef
189.
Yuan H, Lauritsen CG, Kaiser EA, Silberstein SD (2017) CGRP monoclonal antibodies for migraine: rationale and progress. BioDrugs 31(6):487–501PubMedCrossRef
190.
Noseda R, Schain AJ, Melo-Carrillo A, Tien J, Stratton J, Mai F et al (2020) Fluorescently-labeled fremanezumab is distributed to sensory and autonomic ganglia and the dura but not to the brain of rats with uncompromised blood brain barrier. Cephalalgia 40(3):229–240PubMedCrossRef
191.
Charles A (2018) The pathophysiology of migraine: implications for clinical management. Lancet Neurol 17(2):174–182PubMedCrossRef
192.
193.
Sacco S, Bendtsen L, Ashina M, Reuter U, Terwindt G, Mitsikostas D-D et al (2019) European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. J Headache Pain. 20(1):6PubMedPubMedCentralCrossRef
194.
Melo-Carrillo A, Noseda R, Nir R-R, Schain AJ, Stratton J, Strassman AM et al (2017) Selective inhibition of trigeminovascular neurons by fremanezumab: a humanized monoclonal anti-CGRP antibody. J Neurosci 37(30):7149–7163PubMedPubMedCentralCrossRef
195.
Goadsby P, Edvinsson L (1996) Neuropeptide changes in a case of chronic paroxysmal hemicrania—evidence for trigemino-parasympathetic activation. Cephalalgia 16(6):448–450PubMedCrossRef
196.
Lai KL, Niddam D, Fuh JL, Chen SP, Wang YF, Chen WT et al (2017) Flunarizine versus topiramate for chronic migraine prophylaxis: a randomized trial. Acta Neurol Scand 135(4):476–483PubMedCrossRef
197.
Silberstein S, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E (2012) Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the quality standards Subcommittee of the American Academy of neurology and the American headache society. Neurology 78(17):1337–1345PubMedPubMedCentralCrossRef
198.
Pringsheim T, Davenport W, Mackie G, Worthington I, Aubé M, Christie SN et al (2012) Canadian headache society guideline for migraine prophylaxis. Can J Neurol Sci 39(2 Suppl 2):S1–S59PubMed
199.
Guardiani E, Sadoughi B, Blitzer A, Sirois D (2014) A new treatment paradigm for trigeminal neuralgia using botulinum toxin type a. Laryngoscope 124(2):413–417PubMedCrossRef
200.
201.
Do T, Hvedstrup J, Schytz H (2018) Botulinum toxin: a review of the mode of action in migraine. Acta Neurol Scand 137(5):442–451PubMedCrossRef
202.
Edvinsson J, Warfvinge K, Edvinsson L (2015) Modulation of inflammatory mediators in the trigeminal ganglion by botulinum neurotoxin type a: an organ culture study. J Headache Pain 16:555PubMedCrossRef
203.
Gooriah R, Ahmed F (2015) OnabotulinumtoxinA for chronic migraine: a critical appraisal. Therap Clin Risk Manage 11:1003
204.
Gazerani P, Pedersen NS, Staahl C, Drewes AM, Arendt-Nielsen L (2009) Subcutaneous botulinum toxin type a reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin. Pain 141(1–2):60–69PubMedCrossRef
205.
206.
207.
Gaul C, Diener H, Solbach K, Silver N, Straube A, Magis D et al (2014) EHMTI-0364. Non-invasive vagus nerve stimulation using gammacore® for prevention and acute treatment of chronic cluster headache: report from the randomized phase of the preva study. J Headache Pain 15(1)
208.
Silberstein SD, Da Silva AN, Calhoun AH, Grosberg BM, Lipton RB, Cady RK,Goadsby PJ, Simmons K, Mullin C, Saper JR, Liebler EJ (2014) Non-invasive Vagus NerveStimulation for Chronic Migraine Prevention in a Prospective, Randomized, Sham-Controlled Pilot Study (the EVENT Study): report from thedouble-blind phase. Headache 54:1426
209.
Magis D, Schoenen J (2012) Advances and challenges in neurostimulation for headaches. Lancet Neurology 11(8):708–719PubMedCrossRef
210.
Li Y, Yang L, Ni J, Dou Z (2019) Microvascular decompression and radiofrequency for the treatment of trigeminal neuralgia: a meta-analysis. J Pain Res 12:1937PubMedPubMedCentralCrossRef
211.
Blumenfeld A, Ashkenazi A, Napchan U, Bender SD, Klein BC, Berliner R et al (2013) Expert consensus recommendations for the performance of peripheral nerve blocks for headaches–a narrative review. Headache 53(3):437–446PubMedCrossRef
212.
Perloff MD, Chung JS (2018) Urgent care peripheral nerve blocks for refractory trigeminal neuralgia. Am J Emerg Med 36(11):2058–2060PubMedCrossRef
213.
214.
Dach F, Eckeli AL, Ferreira Kdos S, Speciali JG (2015) Nerve block for the treatment of headaches and cranial neuralgias - a practical approach. Headache 55(Suppl 1):59–71PubMedCrossRef
215.
Mathew NT, Kailasam J, Meadors L (2008) Botulinum toxin type a for the treatment of nummular headache: four case studies. Headache 48(3):442–447PubMedCrossRef
Metadata
Title
The fifth cranial nerve in headaches
Authors
J. C. A. Edvinsson
A. Viganò
A. Alekseeva
E. Alieva
R. Arruda
C. De Luca
N. D’Ettore
I. Frattale
M. Kurnukhina
N. Macerola
E. Malenkova
M. Maiorova
A. Novikova
P. Řehulka
V. Rapaccini
O. Roshchina
G. Vanderschueren
L. Zvaune
A. P. Andreou
K. A. Haanes
On behalf of the European Headache Federation School of Advanced Studies (EHF-SAS)
Publication date
01-12-2020
Publisher
Springer Milan
Published in
The Journal of Headache and Pain / Issue 1/2020
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1186/s10194-020-01134-1

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