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The Role of Humoral Mediators in Migraine Headache

Published online by Cambridge University Press:  18 September 2015

A. Fanchamps*
Affiliation:
Medical Counsel, Pharmaceutical Research & Development, Sandoz Ltd., Basle, Switzerland
*
c/o Sandoz Ltd., CH-4002 Basle, Switzerland.
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Summary

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The classical vascular mechanism of migraine attacks demonstrated by Wolff — intracranial vasoconstriction during the prodromal stage and passive vasodilatation of extracranial arteries during the painful phase — has been confirmed by modern methods. Arterial distension is, however, not sufficient to explain the origin of the pain: to give rise to an acute migraineous pain, it must be associated with a lowered pain threshold of the receptors situated in the wall of the affected vessels. A number of humoral factors — plasmakinin, serotonin, histamine — intervene in the chain of events that culminates in migraine headache.

At the start of the attack, the blood platelets release serotonin, the mast cells in the affected area release histamine and proteolytic enzymes that split plasmakininogens to form plas-makinins. Free serotonin and histamine increase capillary permeability and favor transudation of plasmakinin into the vessel walls andperivascular tissues. The combined effect of serotonin and plasmakinin on the vessel wall receptors reduces their pain threshold. On the other hand, the bulk of the released serotonin is excreted as 5-HIAA, and plasma serotonin falls. Since serotonin has a constricting effect on the extracranial arteries and a dilating one on the capillaries, the fall in its plasma level induces hypotonia of these arteries and capillary constriction, which results in a passive distension of the arterial walls. The two factors necessary for the production of pain are thus present: a low pain threshold and vascular distension. In addition to these three main humoral mediators, the part played by tyramine in migraine of alimentary origin, the precipitating effect of estrogen decrease in mentrual migraine and the hypothetical role of prostaglan-dins and prolactin are discussed.

Type
Research Article
Copyright
Copyright © Canadian Neurological Sciences Federation 1974

References

Anthony, M., Hinterberger, H., Lance, J. W. (1967). Plasma serotonin in migraine and stress. Archives of Neurology, 16, 544552.CrossRefGoogle ScholarPubMed
Anthony, M., Hinterberger, H., Lance, J. W. (1969). The possible relationship of serotonin to the migraine syndrome. Research and Clinical Studies of Headache, 2, 2959.Google Scholar
Anthony, M., Lance, J. W. (1971). Histamine and serotonin in cluster headache. Archives of Neurology, 25, 225231.CrossRefGoogle ScholarPubMed
Bartholini, G., Pletscher, A., Gey, K. F. (1961). Diminution of 5-hydroxytryptamine in thrombocytes in vitro by chlorpromazine and related compounds. Experienta, 17, 541542.CrossRefGoogle ScholarPubMed
Bergstroem, S., Carlson, L. A., Weeks, J. R. (1968). The prostaglandins: a family of biologically active lipids. Pharmacological Reviews, 20, 148.Google Scholar
Curran, D. A., Hinterberger, H., Lance, J. W. (1965). Total plasma serotonin, 5-hydroxyindoleacetic acid and p-hydroxy-m-methoxymandelic acid excretion in normal and migrainous subjects. Brain, London, 88, 9971008.CrossRefGoogle ScholarPubMed
Dalsgaard-Neilsen, T., Genefke, I. K. (1973). Serotonin (5-hydroxytryptamine) release and uptake by platelets from healthy persons and migrainous patients in attackfree intervals.Meeting Scandinavian Migraine Society, Copenhagen, October 56, 1973.Google Scholar
Genefke, I. K., Dalsgaard Nielsen, T. (1973). The effect of tyramine on the transport of 5-hydroxytryptamine in blood platelets. Acta pharmacologica et toxicologica, 33, 7478.CrossRefGoogle Scholar
Graham, J. R., Wolff, H. G. (1937). Mechanism of migraine headache and action of ergotamine tartrate. The Proceedings of the Association for Research in Nervous and Mental Disease, 18, 638669.Google Scholar
Hanington, E. (1967). Preliminary report on tyramine headache. British Medical Journal, 2, 550551.CrossRefGoogle Scholar
Hanington, E., Horn, M., Wilkinson, M. (1970). Further observations on the effects of tyramine. Background to Migraine (W. Heinemann, London), 3, 113119.Google Scholar
Hilton, B. P., Cumings, J. N. (1972). 5-hydroxytryptamine levels and platelet aggregation responses in subjects with acute migraine headache. Journal of Neurology, Neurosurgery and Psychiatry, 35, 505509.Google ScholarPubMed
Hopsu, V. K., Glenner, G. G. (1963). Further observations on histochemical esterase and amidase activities with similarities to trypsin. Journal of His-tochemistry and Cytochemistry 11 520528.CrossRefGoogle Scholar
Horrobin, D. F. (1973). Prevention of migraine by reducing prolactin levels? The Lancet, 1, 777.CrossRefGoogle ScholarPubMed
Kangasniemi, P., Riekkinen, P., Rinne, U. K. (1972a). KalHkrein-like esterase and peptidase activities in CSF during migraine attacks and free intervals. Headache, 12, 6668.CrossRefGoogle ScholarPubMed
Kangasniemi, P., Sonninen, V., Rinne, U. K. (1972b). Excretion of free and conjugated 5-HIAA and VMA in urine and concentration of 5-HIAA and HVA in CSF during migraine attacks and free intervals. Headache, 12, 6265.CrossRefGoogle ScholarPubMed
Kimball, R. W., Friedman, A. P., Vallejo, E. (1960). Effect of serotonin in migraine patients. Neurology, 10, 107111.CrossRefGoogle ScholarPubMed
Lance, J. W. (1969). The mechanism and management of headache. Butterworth, London.Google Scholar
Lance, J. W., Anthony, M., Gonski, A. (1967). Serotonin, the carotid body, and cranial vessels in migraine. Archives of Neurology, 16, 553558.CrossRefGoogle ScholarPubMed
Neuhold, K., Taeschler, M. (1963). Ueber die Rolle des Serotonin bei dem durch intraperitoneale Injektion von Essigsäure ausgelösten Schmerzphänomen bei der Maus. Naunyn Schmiedeberg's Archiv für experimentelle Pathologie und Pharmakologie, 245, 130131.CrossRefGoogle Scholar
O'brien, M. D. (1971). Cerebral blood changes in migraine. Headache, 10, 130143.CrossRefGoogle ScholarPubMed
O'brien, M. D. (1971). The relationship between aura symptoms and cerebral blood flow changes in the prodrome of migraine. Proceedings of the International Headache Symposium, Elsinore, Denmark, 1618, May 1971. Ed. Dalessio, by: D. J., Dalsgaard-Nielsen, T., Diamond, S., pp. 141143.Google Scholar
Ostfeld, A. M., Goodell, H., Wolff, H. G. (1958). Studies in headache mechanisms. Archives of Internal Medicine, 101, 755760.CrossRefGoogle ScholarPubMed
Owen, D. A. A., Herd, J. K., Kal-Berer, F., Pacha, W., Salzmann, R. (1971). The influence of ergotamine and methysergide on the storage of biogenic amines. Proceedings of the International Headache Symposium, Elsinore, Denmark, 1618, May 1971. Ed. by: Dalessio, D. J., Dalsgaard-Nielsen, T., Diamond, S., pp. 201203.Google Scholar
Perrault, M. (1963). Migraines sévères, I.M.A.O. et methysergide. Le Progrès Médical, 91, 413422.Google Scholar
Roemer, D. (1965 and 1969). Biological and Medical Research, Sandoz Ltd., Basle, personal communication.Google Scholar
Sandler, M. (1972). Migraine: a pulmonary disease? The Lancet 1, 618619.CrossRefGoogle Scholar
Sandler, M., Youdim, M. B. H., Southgate, J., Hanington, E. (1970). The role of tyramine in migraine: some possible biochemical mechanisms.Background to Migraine (W. Heinemann, London), 3, 103112.Google Scholar
Salzmann, R., Kalberer, F. (1973). Antimigraine drugs and storage of serotonin.Background to Migraine (W. Heinemann, London), 5, 6372.Google Scholar
Sicuteri, F. (1963). Mast cells and their active substances: their role in the pathogenesis of migraine. Headache, 3, 8692.CrossRefGoogle ScholarPubMed
Sicuteri, F. (1973). The ingestion of serotonin precursors (L-5-hydroxytrypto-phan and L-tryptophan) improves migraine headache. Headache, 13, 1922.CrossRefGoogle ScholarPubMed
Sicuteri, F., Fanciullacci, M., Franchi, G., DEL Bianco, P. L. (1965). Serotonin - bradykinin potentiation on the pain receptors in man. Life Sciences, 4, 309316.CrossRefGoogle ScholarPubMed
Sicuteri, F., Testi, A., Anselmi, B. (1961). Biochemical investigations in headache: increase in the hydroxyin-doleacetic acid excretion during migraine attacks. International Archives of Allergy and applied Immunology, 19, 5558.CrossRefGoogle Scholar
Skinhβj, E. (1971). The value of regional cerebral blood flow studies in migraine research. Proceedings of the International Headache Symposium, Elsinore, Denmark, 1618, May 1971. Ed. by: Dalessio,, D. J.Dalsgaard-Nielsen, T., Diamond, S., pp. 201203.Google Scholar
Skinhβj, E., Paulson, O. B. (1969). Regional blood flow in internal carotid distribution during migraine attack. British Medical Journal, 3, 569570.CrossRefGoogle Scholar
Somerville, B. W. (1972). The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology, 22, 355365.CrossRefGoogle ScholarPubMed
Wolff, H. G. (1963). Headache and other head pain. Oxford University Press, New York (1st Edition 1948).Google Scholar