Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00034916.xml
Nervenheilkunde 2019; 38(10): 722-727
DOI: 10.1055/a-0990-2624
DOI: 10.1055/a-0990-2624
Schwerpunkt
Pathophysiologie der Migräne
Aktuelles Verständnis und AusblickPathophysiology of migraineFurther Information
Publication History
Publication Date:
15 October 2019 (online)
ZUSAMMENFASSUNG
Lange Zeit wurde das pathophysiologische Verständnis der Migräne von der Vorstellung geprägt, dass die Gefäße des Kopfes den Schmerz bedingen und die Migräne also ein vaskulärer Kopfschmerz sei. Diese Theorie kann als überholt, zumindest jedoch lückenhaft angesehen werden. Mittlerweile deutet vieles darauf hin, dass es sich bei der Migräne um eine oszillierende Schwellen-/Filterstörung des zentralen Nervensystems handelt, wobei der im Vordergrund stehende Kopfschmerz nur einen Teil des vielfältigen Symptomkomplexes darstellt. Neuere Befunde der funktionellen Bildgebung zeigen zyklische Veränderungen von Aktivitätsmustern im Hypothalamus, Thalamus und Hirnstamm, welche besser erklären können, wie der Kopfschmerz und die migränetypischen Begleitsymptome entstehen. Die zukünftige Grundlagenforschung wird sich auf Kerngebiete im Diencephalon als mögliche Ursprungsorte der Attackengenerierung bei Migräne fokussieren. Große Hoffnung ruhen auf der Erforschung der Wirkweisen neuer Antikörpertherapien, welche helfen werden, molekulare Mechanismen der Schmerzentstehung der Migräne zu entschlüsseln.
ABSTRACT
For a long time, the pathophysiology of migraine was considered to be of vascular origin and that the intracranial vessels cause the pain and that migraine therefore would be a vascular headache. This theory is not valid any more, or at least not complete. Meanwhile, there is a lot of evidence that migraine is an oscillating disturbance of levels/filters within the central nervous system with the prominent headache as only one symptom in a complex of symptoms. Recent findings in functional imaging show cyclic changes of activities in hypothalamus, thalamus and brainstem which can better explain how the headache and the accompanying symptoms develop. Future basic research will probably focus on nuclei in the diencephalon as probable loci of generating migraine attacks. There is hope that the research on the mechanisms of the new antibodies for migraine treatment will help to identify the molecular mechanisms of migraine.
-
Literatur
- 1 Ahn AH. On the temporal relationship between throbbing migraine pain and arterial pulse. Headache 2010; 50 (09) 1507-10
- 2 Amin FM, Asghar MS, Hougaard A. et al Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study. Lancet Neurol 2013; 12 (05) 454-61
- 3 Ashina H, Schytz HW, Ashina M. CGRP in human models of primary headaches. Cephalalgia Int J Headache 2018; 38 (02) 353-60
- 4 Bahra A, Matharu M, Buchel C. et al Brainstem activation specific to migraine headache. The Lancet 2001; 357 9261 1016-7
- 5 Bolay H, Reuter U, Dunn AK. et al Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 2002; 8 (02) 136
- 6 Burstein R, Cutrer MF, Yarnitsky D. The development of cutaneous allodynia during a migraine attack clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine. Brain 2000; 123 Pt 8 1703-9
- 7 Burstein R, Jakubowski M, Garcia-Nicas E. et al Thalamic sensitization transforms localized pain into widespread allodynia. Ann Neurol 2010; 68 (01) 81-91
- 8 Charles A. Vasodilation out of the picture as a cause of migraine headache. Lancet Neurol 2013; 12 (05) 419-20
- 9 Charles A. The pathophysiology of migraine: implications for clinical management. Lancet Neurol 2018; 17 (02) 174-82
- 10 Charles AC, Baca SM. Cortical spreading depression and migraine. Nat Rev Neurol 2013; 9 (11) 637-44
- 11 Deen M, Hougaard A, Hansen HD. et al Association Between Sumatriptan Treatment During a Migraine Attack and Central 5-HT1B Receptor Binding. JAMA Neurol. [Internet]., 2019 May 28 [cited 2019 Jun 24]; Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/2734866
- 12 Denuelle M, Fabre N, Payoux P. et al Hypothalamic Activation in Spontaneous Migraine Attacks. Headache J Head Face Pain 2007; 47 (10) 1418-26
- 13 Diener HC. How can PET scans help us understand headache mechanisms?. Cephalalgia 1999; 19 (Suppl. 23) 15-6
- 14 Ellerbrock I, Engel AK, May A. Microstructural and network abnormalities in headache. Curr Opin Neurol 2013; 26 (04) 353-9
- 15 Ferrari MD, Klever RR, Terwindt GM. et al Migraine pathophysiology: lessons from mouse models and human genetics. Lancet Neurol 2015; 14 (01) 65-80
- 16 Giffin NJ, Lipton RB, Silberstein SD. et al The migraine postdrome. Neurology 2016; 87 (03) 309
- 17 Giffin NJ, Ruggiero L, Lipton RB. et al Premonitory symptoms in migraine. Neurology 2003; 60 (06) 935
- 18 Goadsby PJ. The vascular theory of migraine—a great story wrecked by the facts. Brain 2009; 132 (01) 6-7
- 19 Goadsby PJ. All that is obvious is not clear: What is the origin of throbbing pain in migraine?. Pain 2013; 154 (07) 970
- 20 Goadsby PJ. Primary headache disorders. Neurol Clin Pract 2019; 9 (03) 233
- 21 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
- 22 Goadsby PJ, Holland PR, Martins-Oliveira M. et al Pathophysiology of Migraine: A Disorder of Sensory Processing. Physiol Rev 2017; 97 (02) 553-622
- 23 Goadsby PJ, Wietecha LA, Dennehy EB. et al Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain [Internet]., 2019 [cited 2019 Jun 7]; Available from: https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awz134/5498736
- 24 Hadjikhani N, Sanchez Del Rio M. et al Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U A 2001; 98 (08) 4687-92
- 25 Hansen JM, Lipton RB, Dodick DW. et al Migraine headache is present in the aura phase. Neurology 2012; 79 (20) 2044
- 26 Hebestreit J, May A. No effect of metoprolol on central trigeminal pain processing in patients and healthy subjects: A within-subject design. 2017 submitted
- 27 Hebestreit J, May A. Topiramate modulates trigeminal pain processing in thalamo-cortical networks in humans after single dose administration. 2017 PLOS-1, in press
- 28 Humphrey P, Goadsby P. The Mode of Action of Sumatriptan is Vascular? A Debate. Cephalalgia 1994; 14 (06) 401-10
- 29 Humphrey PPA, Feniuk W, Perren MJ. et al Serotonin and Migraine. Ann N Y Acad Sci 1990; 600 (01) 587-98
- 30 Kaube H, Hoskin KL, Goadsby PJ. Inhibition by sumatriptan of central trigeminal neurones only after blood-brain barrier disruption. Br J Pharmacol 1993; 109 (03) 788-92
- 31 Kelman L. The Postdrome of the Acute Migraine Attack. Cephalalgia 2006; 26 (02) 214-20
- 32 Khan S, Amin FM, Christensen CE. et al Meningeal contribution to migraine pain: a magnetic resonance angiography study. Brain 2019; 142 (01) 93-102
- 33 Kröger IL, May A. Triptan-induced disruption of trigemino-cortical connectivity. Neurology 2015; 84 (21) 2124
- 34 Kruuse C, Thomsen LL, Birk S. et al Migraine can be induced by sildenafil without changes in middle cerebral artery diameter. Brain 2003; 126 (01) 241-7
- 35 Kuca B, Silberstein SD, Wietecha L. et al Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study. Neurology 2010; 91 (24) e2222-32
- 36 Leao AAP. Spreading depression of activity in the cerebral cortex. J Neurophysiol 1944; 7 (06) 359-90
- 37 May A. Pearls and pitfalls: Neuroimaging in headache. Cephalalgia 2013; 33 (08) 554-65
- 38 May A. Understanding migraine as a cycling brain syndrome: reviewing the evidence from functional imaging. Neurol Sci 2017; 38 (01) 125-30
- 39 Mirza AF, Mo J, Holt JL. et al Is There a Relationship between Throbbing Pain and Arterial Pulsations?. J Neurosci 2012; 32 (22) 7572-6
- 40 Mo J, Maizels M, Ding M. et al Does throbbing pain have a brain signature?. PAIN 2013; 154 (07) 1150
- 41 Nelson DL, Phebus LA, Johnson KW. et al Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan. Cephalalgia 2010; 30 (10) 1159-69
- 42 Olesen J, Larsen B, Lauritzen M. Focal hyperemia followed by spreading oligemia and impaired activation of rcbf in classic migraine. Ann Neurol 1981; 9 (04) 344-52
- 43 Peng K-P, May A. Quantitative sensory testing in migraine patients must be phase-specific. Pain 2018; 159 (11) 2414-6
- 44 Peng K-P, May A. Migraine understood as a sensory threshold disease. PAIN 2019; 160 (07) 1494
- 45 Petersen K, Birk S, Lassen L. et al The CGRP-Antagonist, BIBN4096BS Does not Affect Cerebral or Systemic Haemodynamics in Healthy Volunteers. Cephalalgia 2005; 25 (02) 139-47
- 46 Rahmann A, Wienecke T, Hansen J. et al Vasoactive Intestinal Peptide Causes Marked Cephalic Vasodilation, but does not Induce Migraine. Cephalalgia 2008; 28 (03) 226-36
- 47 Russell MB, Ducros A. Sporadic and familial hemiplegic migraine: pathophysiological mechanisms, clinical characteristics, diagnosis, and management. Lancet Neurol 2011; 10 (05) 457-70
- 48 Schoonman GG, van der Grond J, Kortmann C. et al Migraine headache is not associated with cerebral or meningeal vasodilatation—a 3 T magnetic resonance angiography study. Brain 2000; 131 (08) 2192-200
- 49 Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain 2016; 139 (07) 1987-93
- 50 Schumacher GA, Wolff HG. Experimental studies on headache. Arch Neurol Psychiatry 1941; 45 (02) 199-214
- 51 Schytz HW, Birk S, Wienecke T. et al PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain 2009; 132 (01) 16-25
- 52 Shevel E. The Extracranial Vascular Theory of Migraine—A Great Story Confirmed by the Facts. Headache J Head Face Pain 2011; 51 (03) 409-17
- 53 Stankewitz A, Aderjan D, Eippert F. et al Trigeminal nociceptive transmission in migraineurs predicts migraine attacks. J Neurosci Off J Soc Neurosci 2011; 31 (06) 1937-43
- 54 Stewart WF, Wood C, Reed ML. et al Cumulative lifetime migraine incidence in women and men. Cephalalgia 2008; 28 (11) 1170-8
- 55 Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in Migraine. Drugs 2000; 60 (06) 1259-87
- 56 Tunis MM, Wolff HG. Analysis of cranial artery pulse waves in patients with vascular headache of the migraine type. Am J Med Sci 1952; 224 (05) 565-8
- 57 Voss T, Lipton RB, Dodick DW. et al A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine. Cephalalgia 2016; 36 (09) 887-98
- 58 Weiller C, May A, Limmroth V. et al Brain stem activation in spontaneous human migraine attacks. Nat Med 1995; 1 (07) 658
- 59 Wolff HG. Wolff’s Headache and other Head Pain. 3 rd Edition. Oxford: University Press; 1972
- 60 Wolff HG, Tunis MM, Goodell H. STUDIES ON HEADACHE: Evidence of Tissue Damage and Changes in Pain Sensitivity in Subjects with Vascular Headaches of the Migraine Type. AMA Arch Intern Med 1953; 92 (04) 478-84
- 61 Woods RP, Iacoboni M, Mazziotta JC. Brief report: bilateral spreading cerebral hypoperfusion during spontaneous migraine headache. N Engl J Med 1994; 331 (25) 1689-92