Abstract
Given the clinical presentation and neuroscientific evidence, it is undisputed that the hypothalamus plays a central role in cluster headache (CH) pathogenesis [1, 2]. But does an activation of the hypothalamus suffice in generating the perception of pain or are peripheral structures required? This chapter revolves around the question of nociceptive input: where does the pain in CH originate from? This is a question which, as of yet, has no conclusive answer [2–5]. However, looking at previous research and clinical observations, we might be able to make some assumptions and pose some qualified guesses.
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References
Hoffmann J, May A. Diagnosis, pathophysiology, and management of cluster headache. Lancet Neurol. 2018;17(1):75–83.
Barloese MCJ. The pathophysiology of the trigeminal autonomic cephalalgias, with clinical implications. Clin Auton Res. 2018;28(3):315–24.
Goadsby PJ. Pathophysiology of cluster headache: a trigeminal autonomic cephalgia. Lancet Neurol. 2002;1(4):251–7.
Leone M, Proietti CA. Advances in the understanding of cluster headache. Expert Rev Neurother. 2017;17(2):165–72.
May A. Cluster headache: pathogenesis, diagnosis, and management. Lancet. 2005;366(9488):843–55.
Bogduk N. Anatomy and physiology of headache. Biomed Pharmacother. 1995;49(10):435–45.
Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97(2):553–622.
Schulte LH, Sprenger C, May A. Physiological brainstem mechanisms of trigeminal nociception: an fMRI study at 3T. NeuroImage. 2016;124(Pt A):518–25.
Liu Y, Broman J, Zhang M, Edvinsson L. Brainstem and thalamic projections from a craniovascular sensory nervous centre in the rostral cervical spinal dorsal horn of rats. Cephalalgia. 2009;29(9):935–48.
Malick A, Burstein R. Cells of origin of the trigeminohypothalamic tract in the rat. J Comp Neurol. 1998;400(1):125–44.
Williams MN, Zahm DS, Jacquin MF. Differential foci and synaptic organization of the principal and spinal trigeminal projections to the thalamus in the rat. Eur J Neurosci. 1994;6(3):429–53.
DaSilva AFM, Becerra L, Makris N, Strassman AM, Gonzalez RG, Geatrakis N, Borsook D. Somatotopic activation in the human trigeminal pain pathway. J Neurosci. 2002;22(18):8183–92.
Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007;55(3):377–91.
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(4):2078–112.
Bartsch T, Levy MJ, Knight YE, Goadsby PJ. Differential modulation of nociceptive dural input to [hypocretin] orexin A and B receptor activation in the posterior hypothalamic area. Pain. 2004;109(3):367–78.
May A, Goadsby PJ. The trigeminovascular system in humans: pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation. J Cereb Blood Flow Metab. 1999;19(2):115–27.
Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629–808.
Horven I, Sjaastad O. Cluster headache syndrome and migraine. Ophthalmological support for a two-entity theory. Acta Ophthalmol. 1977;55(1):35–51.
Barriga FJ, Sánchez-del-Río M, Barón M, Dobato J, Gili P, Yangüela J, Bueno A, Pareja JA. Cluster headache: interictal asymmetric increment in intraocular pressure elicited by Valsalva manoeuvre. Cephalalgia. 2004;24(3):185–7.
Evers S, Sörös P, Brilla R, Gerding H, Husstedt IW. Cluster headache after orbital exenteration. Cephalalgia. 1997;17(6):680–2.
Rogado AZ, Graham JR, Graham P. Headache rounds—through a glass darkly. Headache. 1979;19(2):058–62.
Fanciullacci M. When cluster headache was called histaminic cephalalgia (Horton’s headache). J Headache Pain. 2006;7(4):231–4.
May A, Bahra A, Büchel C, Frackowiak RS, Goadsby PJ. PET and MRA findings in cluster headache and MRA in experimental pain. Neurology. 2000;55(9):1328–35.
Goadsby PJ, Edvinsson L. Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies. Brain J Neurol. 1994;117(Pt 3):427–34.
Ekbom K. Nitroglycerin as a provocative agent in cluster headache. Arch Neurol. 1968;19(5):487–93.
Horton BT. Histaminic cephalgia. J Lancet. 1952;72(2):92–8.
Matharu MS, Goadsby PJ. Persistence of attacks of cluster headache after trigeminal nerve root section. Brain. 2002;125(5):976–84.
Hardebo JE. How cluster headache is explained as an intracavernous inflammatory process lesioning sympathetic fibers. Headache. 1994;34(3):125–31.
Hannerz J. Orbital phlebography and signs of inflammation in episodic and chronic cluster headache. Headache. 1991;31(8):540–2.
Moskowitz MA. Cluster headache: evidence for a pathophysiologic focus in the superior pericarotid cavernous sinus plexus. Headache. 1988;28(9):584–6.
Remahl IN, Waldenlind E, Bratt J, Ekbom K. Cluster headache is not associated with signs of a systemic inflammation. Headache. 2000;40(4):276–82.
Sjaastad O, Rinck P. Cluster headache: MRI studies of the cavernous sinus and the base of the brain. Headache. 1990;30(6):350–1.
Hannerz J, Greitz D, Hansson P, Ericson K. SUNCT may be another manifestation of orbital venous vasculitis. Headache. 1992;32(8):384–9.
Hannerz J. Pathoanatomic studies in a case of Tolosa-Hunt syndrome. Cephalalgia. 1988;8(1):25–30.
Bovim G, Jenssen G, Ericson K. Orbital phlebography: a comparison between cluster headache and other headaches. Headache. 1992;32(8):408–12.
Dirkx THT, Koehler PJ. Post-operative cluster headache following carotid endarterectomy. Eur Neurol. 2017;77(3–4):175–9.
Candeloro E, Canavero I, Maurelli M, Cavallini A, Ghiotto N, Vitali P, Micieli G. Carotid dissection mimicking a new attack of cluster headache. J Headache Pain. 2013;14:84.
Jarrar RG, Black DF, Dodick DW, Davis DH. Outcome of trigeminal nerve section in the treatment of chronic cluster headache. Neurology. 2003;60(8):1360–2.
Classey JD, Bartsch T, Goadsby PJ. Distribution of 5-HT1B, 5-HT1D and 5-HT1F receptor expression in rat trigeminal and dorsal root ganglia neurons: relevance to the selective anti-migraine effect of triptans. Brain Res. 2010;1361:76–85.
Uddman R, Hara H, Edvinsson L. Neuronal pathways to the rat middle meningeal artery revealed by retrograde tracing and immunocytochemistry. J Auton Nerv Syst. 1989;26(1):69–75.
Jürgens TP, May A. Role of sphenopalatine ganglion stimulation in cluster headache. Curr Pain Headache Rep. 2014;18(7):433.
Csati A, Tajti J, Tuka B, Edvinsson L, Warfvinge K. Calcitonin gene-related peptide and its receptor components in the human sphenopalatine ganglion—interaction with the sensory system. Brain Res. 2012;1435:29–39.
Schoenen J, Jensen RH, Lantéri-Minet M, Láinez MJA, Gaul C, Goodman AM, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816–30.
Jürgens TP, Barloese M, May A, Láinez JM, Schoenen J, Gaul C, Goodman AM, Caparso A, Jensen RH. Long-term effectiveness of sphenopalatine ganglion stimulation for cluster headache. Cephalalgia. 2017;37(5):423–34.
Schytz HW, Barløse M, Guo S, Selb J, Caparso A, Jensen R, Ashina M. Experimental activation of the sphenopalatine ganglion provokes cluster-like attacks in humans. Cephalalgia. 2013;33(10):831–41.
Sanders M, Zuurmond WW. Efficacy of sphenopalatine ganglion blockade in 66 patients suffering from cluster headache: a 12- to 70-month follow-up evaluation. J Neurosurg. 1997;87(6):876–80.
Narouze S, Kapural L, Casanova J, Mekhail N. Sphenopalatine ganglion radiofrequency ablation for the management of chronic cluster headache. Headache. 2009;49(4):571–7.
Martins IP, Gouveia RG, Antunes JL. Double dissociation between autonomic symptoms and pain in cluster headache. Cephalalgia. 2005;25(5):398–400.
Nemeroff CB, Mayberg HS, Krahl SE, McNamara J, Frazer A, Henry TR, George MS, Charney DS, Brannan SK. VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology. 2006;31(7):1345–55.
Foley JO, DuBois FS. Quantitative studies of the vagus nerve in the cat. I. The ratio of sensory to motor fibers. J Comp Neurol. 1937;67(1):49–67.
Dorr AE, Debonnel G. Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission. J Pharmacol Exp Ther. 2006;318(2):890–8.
Cunningham JT, Mifflin SW, Gould GG, Frazer A. Induction of c-Fos and DeltaFosB immunoreactivity in rat brain by Vagal nerve stimulation. Neuropsychopharmacology. 2008;33(8):1884–95.
Gwyn DG, Leslie RA, Hopkins DA. Observations on the afferent and efferent organization of the vagus nerve and the innervation of the stomach in the squirrel monkey. J Comp Neurol. 1985;239(2):163–75.
Goadsby PJ, de Coo IF, Silver N, Tyagi A, Ahmed F, Gaul C, et al. Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: a randomized, double-blind, sham-controlled ACT2 study. Cephalalgia. 2018;38(5):959–69.
Akerman S, Simon B, Romero-Reyes M. Vagus nerve stimulation suppresses acute noxious activation of trigeminocervical neurons in animal models of primary headache. Neurobiol Dis. 2017;102:96–104.
Frangos E, Komisaruk BR. Access to vagal projections via cutaneous electrical stimulation of the neck: fMRI evidence in healthy humans. Brain Stimul. 2017;10(1):19–27.
Robert C, Bourgeais L, Arreto C-D, Condes-Lara M, Noseda R, Jay T, Villanueva L. Paraventricular hypothalamic regulation of trigeminovascular mechanisms involved in headaches. J Neurosci. 2013;33(20):8827–40.
Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain J Neurol. 2016;139(Pt 7):1987–93.
Schulte LH. Hypothalamus as a mediator of chronic migraine: evidence from high-resolution fMRI. Neurology. 2017;88(21):2011–6.
May A. New insights into headache: an update on functional and structural imaging findings. Nat Rev Neurol. 2009;5(4):199–209.
May A, Ashburner J, Büchel C, McGonigle DJ, Friston KJ, Frackowiak RS, Goadsby PJ. Correlation between structural and functional changes in brain in an idiopathic headache syndrome. Nat Med. 1999;5(7):836–8.
Lodi R, Pierangeli G, Tonon C, Cevoli S, Testa C, Bivona G. Study of hypothalamic metabolism in cluster headache by proton MR spectroscopy. Neurology. 2006;66(8):1264–6.
May A, Bahra A, Büchel C, Frackowiak RS, Goadsby PJ. Hypothalamic activation in cluster headache attacks. Lancet. 1998;352(9124):275–8.
Leone M, Franzini A, Bussone G. Stereotactic stimulation of posterior hypothalamic gray matter in a patient with intractable cluster headache. N Engl J Med. 2001;345(19):1428–9.
Bartsch T, Pinsker MO, Rasche D, Kinfe T, Hertel F, Diener HC, et al. Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series. Cephalalgia. 2008;28(3):285–95.
Leone M, Franzini A, Broggi G, Mea E, Cecchini AP, Bussone G. Acute hypothalamic stimulation and ongoing cluster headache attacks. Neurology. 2006;67(10):1844–5.
Leone M, Bussone G. Pathophysiology of trigeminal autonomic cephalalgias. Lancet Neurol. 2009;8(8):755–64.
Leone M, Franzini A, Broggi G, May A, Bussone G. Long-term follow-up of bilateral hypothalamic stimulation for intractable cluster headache. Brain J Neurol. 2004;127(Pt 10):2259–64.
Schoenen J. Sphenopalatine ganglion stimulation in neurovascular headaches. Prog Neurol Surg. 2015;29:106–16.
May A, Schwedt TJ, Magis D, Pozo-Rosich P, Evers S, Wang S-J. Cluster headache. Nat Rev Dis Primers. 2018;4:18006.
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Nielsen, T., May, A., Jürgens, T.P. (2020). Some Observations About the Origin of the Pain in Cluster Headache. In: Leone, M., May, A. (eds) Cluster Headache and other Trigeminal Autonomic Cephalgias. Headache. Springer, Cham. https://doi.org/10.1007/978-3-030-12438-0_8
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