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Der Schmerz

, Volume 10, Issue 3, pp 114–120 | Cite as

Tiermodelle und ihre Konsequenzen für die therapie der Migräne

  • H. Kaube
  • V. Limmroth
Übersichten

Zusammenfassung

Die Pathophysiologie der Migräne ist bis heute nur bruchstückhaft bekannt, und es existiert kein einheitliches Tiermodell. Dennoch gelang es in den letzten 10 Jahren aufgrund tierexperimenteller Untersuchungen die Wirkorte- und Mechanismen von Medikamenten zur Attackentherapie der Migräne zur charakterisieren. Es gilt inzwischen als gesichert, daß es während der Migräneattacke zu einer Aktivierung des trigeminalen Systems kommt. Das Modell der neurogenen Entzündung durch Stimulation des Ganglion Gasseri oder systemische Applikation von Capsaicin erlaubt die Untersuchung der inhibierenden Interaktion von Migränemitteln mit peripheren trigeminalen Fasern, die während der Migräneattacke durch Freisetzung von vasoaktiven und agogenen Neuropeptiden (Substanz P und CGRP) einen aseptischen Entzündungsprozeß an den Meningen aufrechterhalten. Das Modell der Sinus sagittalis superior Stimulation befaßt sich mit der zentralen Modulation und Transmission von trigeminalen Schmerzreizen im Hirnstamm (Nc. caudalis). So konnte für die Migränemittel Ergotamin, Sumatriptan aber auch Acetylsalicylsäure ein zentraler Angriffspunkt im Hirnstamm demonstriert werden. Als Erklärung für die langsam wandernden neurologischen Reiz- und Ausfalls-symptome während Migräneat-tacken mit Aura wird häufig die—aus tierexperimentellen Untersuchungen bekannte—“corticale spreading depression” angeführt. Ihre Existenz ist beim Menschen bis jetzt weiterhin nicht gesichert. Die obengenannten Modelle ermöglichen schon heute die gezieltere Entwicklung von Migränemitteln und haben wesentlich zu unserem Verständnis über die pathophysiologischen Abläufe während der akuten Migräneattacke beigetragen.

Schlüsselwörter

Migräne Schmerz Trigeminus Pathophysiologie Substanz P CGRP Ergotamin Sumatriptan 

Animal models and their results in relation to the therapy of migraine

Abstract

Until now, our understanding of migraine pathophysiology has been fairly incomplete. So far no animal model has allowed an explanation of all facets of the clinically heterogenous condition migraine. However, it is now generally accepted that the migraine headache is due to activation of the trigeminal system. The model of neurogenic inflammation after stimulation of the trigeminal ganglion or systemic administration of capsaicin allows study of the inhibitory interactions between antimigraine compounds and peripheral trigeminal fibre terminals that sustain a sterile meningeal inflammation through release of alogenic and vasoactive neuropeptides, such as substance P and calcitonin gene-related peptide. Studies with the model of superior sagittal sinus stimulation have revealed central actions of antimigraine agents such as ergotamine and sumatriptan, but also acetylsalicylic acid on neurotransmission of trigeminal nociceptive input in the brainstem. A likely explanation for the slowly progressing neurological deficits is cortical spreading depression (CSD), which can easily be elicited in many species. However, CSD has not been observed in vivo in humans. The described models strongly influenced the development of new medications for migraine treatment and have improved our understanding of migraine pathophysiology.

Key words

Review Migraine Pain Pathophysiology Trigeminal Cortical spreading depression Substance P CGRP Ergotamine Sumatriptan 

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • H. Kaube
    • 1
  • V. Limmroth
    • 2
  1. 1.Neurologische UniversitätsklinikEssen
  2. 2.Harvard Medical SchoolBostonUSA

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