Journal of Neurology

, Volume 238, Supplement 1, pp S2–S5 | Cite as

What is migraine? Controversy and stalemate in migraine pathophysiology

  • J. Edmeads
Review Of Migraine And Its Therapy


Theories of migraine pathophysiology have evolved from the realms of the supernatural into the scientific arena but their further evolution seems delayed by unproductive controversy about whether or not migraine is primarily a vascular or a neurological dysfunction. This conceptual deadlock needs to be transcended by thinking beyond the neural and vascular systems, and by identifying mechanisms that could affect both to produce the characteristic clinical phenomena of migraine. One theoretical model envisages 5-hydroxytryptamine (serotonin; 5-HT) as a link between the neural and vascular systems, with global alteration of serotonergic neurotransmission affecting not only these systems, but the gastrointestinal tract as well, with incidental reverberations on platelet function. Such altered serotonergic transmission might originate from altered 5-HT receptor dynamics, a molecular change in turn produced by genetic mechanisms. Recognition of the importance of 5-HT receptor function in migraine, most notably that agonists of 5-HT1 receptors abort acute migraine and that antagonists of 5-HT2 receptors prevent migraine, may lead to significant therapeutic advances. The possibility that the “trigeminovascular system” might be the end-stage mechanism that these serotonergic changes detonate to produce the painful reverberations of migraine headache is also important. Seeking ways to muffle these reverberations, or to insulate the system itself from the action of external influences (likely through further study of peptidergic transmission and receptors) might result in more drugs that will abort or prevent migraine.

Key words

Migraine pathophysiology Serotonin receptors Neuropeptides 


  1. 1.
    Anthony M, Hinterberger H, Lance JW (1969) The possible relationship of serotonin to the migraine syndrome. In: Friedman AP (ed) Research and clinical studies in headache, vol 2. Karger, New York, pp 29–59Google Scholar
  2. 2.
    Curzon G, Barie M, Wilkinson MIP (1969) Relationship between headache and amine changes after administration of reserpine to migrainous patients. J Neurol Neurosurg Psychiatry 32:555–561Google Scholar
  3. 3.
    D'Andrea G, Toldo M, Cortelazzo S, Milone FF (1982) Platelet activity in migraine. Headache 22:207–212Google Scholar
  4. 4.
    Davies PTG, Steiner TJ (1990) Serotonin S2 receptors and migraine: a study with the selective antagonist ICI 169,369. Headache 30:340–343Google Scholar
  5. 5.
    Gawel M, Burkitt M, Clifford Rose F (1979) The platelet release reaction during migraine attacks. Headache 19:323–327Google Scholar
  6. 6.
    Graham JR, Wolff HG (1938) Mechanism of migraine headache and action of ergotamine tartrate. Arch Neurol Psychiatry 39:737–763Google Scholar
  7. 7.
    Hanington E, Jones RJ, Amess JAL, Wachowicz B (1981) Migraine — a platelet disorder. Lancet II:720–723Google Scholar
  8. 8.
    Hilton BP, Cumings JN (1972) 5-Hydroxytryptamine levels and platelet aggregation responses in subjects with acute migraine headache. J Neurol Neurosurg Psychiatry 35:505–509Google Scholar
  9. 9.
    Humphrey PPA, Feniuk W, Perren MJ (1990) Anti-migraine drugs in development: advances in serotonin receptor pharmacology. Headache 30:12–16Google Scholar
  10. 10.
    Kimball RW, Friedman AP, Vallejo E (1960) Effect of serotonin in migraine patients. Neurology 10:107–111Google Scholar
  11. 11.
    Lance JW, Lambert GA, Goadsby PJ, Duckworth JW (1983) Brainstem influences on the cephalic circulation: experimental data from cat and monkey of relevance to the mechanism of migraine. Headache 23:258–265Google Scholar
  12. 12.
    Lashley KS (1941) Patterns of cerebral integration indicated by the scotomas of migraine. Arch Neurol Psychiatry 46:259–264Google Scholar
  13. 13.
    Leao AAP (1944) Spreading depression of activity in cerebral cortex. J Neurophysiol 7:359–390Google Scholar
  14. 14.
    Moskowitz MA (1984) The neurobiology of vascular head pain. Ann Neurol 16:157–168Google Scholar
  15. 15.
    Moynihan B (1920) On advances in science. Surg Gynecol Obstet 31:549–552Google Scholar
  16. 16.
    Olesen J, Larsen B, Lauritzen M (1981) Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine. Ann Neurol 9:344–352Google Scholar
  17. 17.
    Peroutka SJ (1990) The pharmacology of current anti-migraine drugs. Headache 30:5–11Google Scholar
  18. 18.
    Schiller F (1975) The migraine tradition. Bull Hist Med 49:1–19Google Scholar
  19. 19.
    Schumacher JA, Wolff HG (1941) Experimental studies on headache. Arch Neurol Psychiatry 45:199–214Google Scholar
  20. 20.
    Skyhøj Olsen T (1990) Migraine with and without aura: the same disease due to cerebral vasospasm of different intensity. A hypothesis based on CBF studies during migraine. Headache 30:269–272Google Scholar
  21. 21.
    Steiner TJ, Joseph R, Clifford Rose F (1985) Migraine is not a platelet disorder. Headache 25:434–440Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • J. Edmeads
    • 1
  1. 1.University of TorontoTorontoCanada

Personalised recommendations