Pathophysiology of Migraine

The cause and pathophysiology of migraine are not well understood. Over the years research into migraine pathophysiology has focused on the physiology and pharmacology of the headache, the changes in cerebral cortex associated with the symptoms of the aura, and more recently the genetics underlying the migraine syndromes. In this discussion, the neuroanatomical structures activated during migraine attacks, the traditional theories of migraine that serve as the foundation for current research, and the essential findings from current migraine pathophysiological research will be reviewed. Investigations in migraine can be divided into those related to the brain events initiating a migraine attack, those examining the mechanisms of activation and transmission within trigeminal afferent neurons, and those focused on the effect of and the modulation of nociception trigeminal input within the central nervous system.

[1]  A. May,et al.  Cortical Excitability and Migraine , 2007, Cephalalgia : an international journal of headache.

[2]  S. Aurora,et al.  Brainstem Dysfunction in Chronic Migraine as Evidenced by Neurophysiological and Positron Emission Tomography Studies * , 2007, Headache.

[3]  TD Rozen.  Vanishing Cerebellar Infarcts in a Migraine Patient , 2007, Cephalalgia : an international journal of headache.

[4]  Liad Hollender,et al.  High-Resolution In Vivo Imaging of the Neurovascular Unit during Spreading Depression , 2007, The Journal of Neuroscience.

[5]  J. Schoenen,et al.  Electrophysiological response patterns of primary sensory cortices in migraine , 2006, The Journal of Headache and Pain.

[6]  G. Carmignoto,et al.  Astrocyte control of synaptic transmission and neurovascular coupling. , 2006, Physiological reviews.

[7]  G. Frisoni,et al.  Shunt-associated migraine responds favorably to atrial septal repair: a case-control study. , 2006, Stroke.

[8]  A. Oterino,et al.  Association of migraine and ESR1 G325C polymorphism , 2006, Neuroreport.

[9]  T. Strom,et al.  Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine , 2005, The Lancet.

[10]  S. Gentile,et al.  Association between migraine and HLA–DRB1 gene polymorphisms , 2005, The Journal of Headache and Pain.

[11]  J. V. Olsen,et al.  Migraine headache relief after transcatheter closure of patent foramen ovale. , 2005, Journal of the American College of Cardiology.

[12]  R. Lea,et al.  Investigation of hormone receptor genes in migraine , 2005, Neurogenetics.

[13]  P. Goadsby,et al.  Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial nucleus: a role in migraine? , 2004, Brain : a journal of neurology.

[14]  Karl J. Friston,et al.  A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate. , 2004, Brain : a journal of neurology.

[15]  Hongwei Jin,et al.  Cortical spreading depression activates and upregulates MMP-9. , 2004, The Journal of clinical investigation.

[16]  R. Lea,et al.  The estrogen receptor 1 G594A polymorphism is associated with migraine susceptibility in two independent case/control groups , 2004, Neurogenetics.

[17]  M. Ferrari,et al.  Migraine as a risk factor for subclinical brain lesions. , 2004, JAMA.

[18]  L. Grimaldi,et al.  Association between the tumor necrosis factor-α −308 G/A gene polymorphism and migraine , 2004, Neurology.

[19]  J. Gulcher,et al.  Localization of a gene for migraine without aura to chromosome 4q21. , 2003, American journal of human genetics.

[20]  S. Cherny,et al.  Significant linkage to migraine with aura on chromosome 11q24. , 2003, Human molecular genetics.

[21]  S. Aurora,et al.  The Threshold for Phosphenes is Lower in Migraine , 2003, Cephalalgia : an international journal of headache.

[22]  K. Nakashima,et al.  Glutathione S-Transferase Polymorphisms: Susceptibility to Migraine without Aura , 2003, European Neurology.

[23]  E. Ergul,et al.  Association of the C677T and A1298C polymorphisms in the 5,10 methylenetetrahydrofolate reductase gene in patients with migraine risk. , 2003, Brain research. Molecular brain research.

[24]  C. Scapoli,et al.  A genetic association study of migraine with dopamine receptor 4, dopamine transporter and dopamine-beta-hydroxylase genes , 2003, Neurological Sciences.

[25]  A. Ballabio,et al.  Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2 , 2003, Nature Genetics.

[26]  L. Forsgren,et al.  Identification of a susceptibility locus for migraine with and without aura on 6p12.2-p21.1 , 2002, Neurology.

[27]  David Borsook,et al.  Somatotopic Activation in the Human Trigeminal Pain Pathway , 2002, The Journal of Neuroscience.

[28]  V. Nagesh,et al.  Functional MRI-BOLD of brainstem structures during visually triggered migraine , 2002, Neurology.

[29]  J. Urenjak,et al.  Nitric Oxide Formation during Cortical Spreading Depression is Critical for Rapid Subsequent Recovery of Ionic Homeostasis , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[30]  Jeanette C Papp,et al.  A susceptibility locus for migraine with aura, on chromosome 4q24. , 2002, American journal of human genetics.

[31]  Y. Bayazıt,et al.  Significance of the catechol-O-methyltransferase gene polymorphism in migraine. , 2001, Brain research. Molecular brain research.

[32]  N Gelman,et al.  Periaqueductal Gray Matter Dysfunction in Migraine: Cause or the Burden of Illness? , 2001, Headache.

[33]  C. Tzourio,et al.  Association between migraine and endothelin type A receptor (ETA −231 A/G) gene polymorphism , 2001, Neurology.

[34]  B. Rosen,et al.  Mechanisms of migraine aura revealed by functional MRI in human visual cortex , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[35]  R. Lea,et al.  Evidence for allelic association of the dopamine β-hydroxylase gene (DBH) with susceptibility to typical migraine , 2000, Neurogenetics.

[36]  D. Yarnitsky,et al.  The development of cutaneous allodynia during a migraine attack clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine. , 2000, Brain : a journal of neurology.

[37]  D. Yarnitsky,et al.  An association between migraine and cutaneous allodynia , 2000, Annals of neurology.

[38]  A. Tuttolomondo,et al.  Angiotensin-Converting Enzyme Gene Deletion Polymorphism Determines an Increase in Frequency of Migraine Attacks in Patients Suffering from Migraine without Aura , 2000, European Neurology.

[39]  B. Rosen,et al.  Perfusion Weighted Imaging During Migraine: Spontaneous Visual Aura and Headache , 1999, Cephalalgia : an international journal of headache.

[40]  Yue Cao,et al.  Functional MRI-BOLD of visually triggered headache in patients with migraine. , 1999, Archives of neurology.

[41]  N. L. Chamberlin,et al.  Cardiovascular and neuronal responses to head stimulation reflect central sensitization and cutaneous allodynia in a rat model of migraine. , 1999, Journal of neurophysiology.

[42]  G. Gessa,et al.  Association between dopamine receptor genes and migraine without aura in a Sardinian sample , 1998, Neurology.

[43]  A. Charles,et al.  Intercellular calcium waves in glia , 1998, Glia.

[44]  D. Nyholt,et al.  Evidence for an X-linked genetic component in familial typical migraine. , 1998, Human molecular genetics.

[45]  R. Burstein,et al.  Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. , 1998, Journal of neurophysiology.

[46]  J. Olesen,et al.  Altered Allelic Distributions of the Serotonin Transporter Gene in Migraine Without Aura and Migraine with Aura , 1998, Cephalalgia.

[47]  B. Rosen,et al.  Perfusion‐weighted imaging defects during spontaneous migrainous aura , 1998, Annals of neurology.

[48]  C Büchel,et al.  Experimental cranial pain elicited by capsaicin: a PET study , 1998, Pain.

[49]  S. Peroutka,et al.  Clinical susceptibility to migraine with aura is modified by dopamine D2 receptor (DRD2) Nco I alleles , 1997, Neurology.

[50]  R. Burstein,et al.  Sensitization of meningeal sensory neurons and the origin of headaches , 1996, Nature.

[51]  Dennis E Bulman,et al.  Familial Hemiplegic Migraine and Episodic Ataxia Type-2 Are Caused by Mutations in the Ca2+ Channel Gene CACNL1A4 , 1996, Cell.

[52]  C. Weiller,et al.  Brain stem activation in spontaneous human migraine attacks , 1995, Nature Medicine.

[53]  B. Siewert,et al.  Acute human stroke studied by whole brain echo planar diffusion‐weighted magnetic resonance imaging , 1995, Annals of neurology.

[54]  J. Mazziotta,et al.  Brief report: bilateral spreading cerebral hypoperfusion during spontaneous migraine headache. , 1994, The New England journal of medicine.

[55]  A. R. Gardner-Medwin,et al.  Journal of Cerebral Blood Flow and Metabolism Magnetic Resonance Imaging of Propagating Waves of Spreading Depression in the Anaesthetised Rat , 2022 .

[56]  Robert Turner,et al.  Functional MRI of the brain. A Report on the SMRM/SMRI workshop held in arlington, virginia june 17–19, 1993 , 1993, Magnetic resonance in medicine.

[57]  M. Moskowitz,et al.  Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[58]  M. Moskowitz,et al.  Expression of c-fos-like immunoreactivity in brainstem after meningeal irritation by blood in the subarachnoid space , 1992, Neuroscience.

[59]  N. Ramadan,et al.  NMR spectroscopic and magnetoencephalographic studies in migraine with aura: support for the spreading depression hypothesis. , 1992, Pathologie-biologie.

[60]  T. Olsen,et al.  Timing and topography of cerebral blood flow, aura, and headache during migraine attacks , 1990, Annals of neurology.

[61]  P. Goadsby,et al.  Vasoactive peptide release in the extracerebral circulation of humans during migraine headache , 1990, Annals of neurology.

[62]  M. Lauritzen,et al.  Ischemia May Be the Primary Cause of the Neurologic Deficits in Classic Migraine , 1990 .

[63]  M. Lauritzen,et al.  Cortical Spreading Depression is Associated with Arachidonic Acid Accumulation and Preservation of Energy Charge , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[64]  S. Levine,et al.  Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 31 NMR spectroscopy , 1989, Neurology.

[65]  J. Olesen,et al.  Delayed hyperemia following hypoperfusion in classic migraine. Single photon emission computed tomographic demonstration. , 1988, Archives of neurology.

[66]  P. Roland,et al.  Focal ischaemia caused by instability of cerebrovascular tone during attacks of hemiplegic migraine. A regional cerebral blood flow study. , 1987, Brain : a journal of neurology.

[67]  M. Jacquin,et al.  Structure-function relationships in rat medullary and cervical dorsal horns. II. Medullary dorsal horn cells. , 1986, Journal of neurophysiology.

[68]  J. Olesen,et al.  Regional cerebral blood flow during migraine attacks by Xenon-133 inhalation and emission tomography. , 1984, Brain : a journal of neurology.

[69]  M. Moskowitz,et al.  Trigeminal projections to supratentorial pial and dural blood vessels in cats demonstrated by horseradish peroxidase histochemistry , 1984, The Journal of comparative neurology.

[70]  Martin Lauritzen,et al.  Changes in regional cerebral blood flow during the course of classic migraine attacks , 1983, Annals of neurology.

[71]  J. Olesen,et al.  Focal hyperemia followed by spreading oligemia and impaired activation of rcbf in classic migraine , 1981, Annals of neurology.

[72]  R Dubner,et al.  Functional properties of neurons in cat trigeminal subnucleus caudalis (medullary dorsal horn). II. Modulation of responses to noxious and nonnoxious stimuli by periaqueductal gray, nucleus raphe magnus, cerebral cortex, and afferent influences, and effect of naloxone. , 1981, Journal of neurophysiology.

[73]  C. Nicholson,et al.  Extracellular ionic variations during spreading depression , 1978, Neuroscience.

[74]  S. Wise,et al.  Cells of origin and terminal distribution of descending projections of the rat somatic sensory cortex , 1977, The Journal of comparative neurology.

[75]  A. A. Leão,et al.  SPREADING DEPRESSION OF ACTIVITY IN THE CEREBRAL CORTEX , 1944 .

[76]  K. Lashley.  PATTERNS OF CEREBRAL INTEGRATION INDICATED BY THE SCOTOMAS OF MIGRAINE , 1941 .

[77]  H. Wolff,et al.  EXPERIMENTAL STUDIES ON HEADACHE: PAIN-SENSITIVE STRUCTURES OF THE HEAD AND THEIR SIGNIFICANCE IN HEADACHE , 1940 .

[78]  M. Moskowitz,et al.  Neuroeffector functions of sensory fibres: implications for headache mechanisms and drug actions , 2004, Journal of Neurology.

[79]  D. Soragna,et al.  A locus for migraine without aura maps on chromosome 14q21.2-q22.3. , 2003, American journal of human genetics.

[80]  J. Olesen,et al.  Migraine can be induced by sildenafil without changes in middle cerebral artery diameter. , 2003, Brain : a journal of neurology.

[81]  S. Peroutka,et al.  Comorbid Migraine with Aura, Anxiety, and Depression Is Associated with Dopamine D2 Receptor (DRD2) NcoI Alleles , 1998, Molecular medicine.

[82]  M F Jacquin,et al.  Intersubnuclear connections within the rat trigeminal brainstem complex. , 1990, Somatosensory & motor research.

[83]  R. Young,et al.  Specialized Features of the Trigeminal Nerve and Its Central Connections , 1981 .

[84]  A. van Harreveld,et al.  Mechanisms involved in spreading depression. , 1973, Journal of neurobiology.