Veränderung im trigeminalen Schmerzsystem nach chemischer Stimulation der Dura mater

Zusammenfassung

Die Pathophysiologie chronischer Kopfschmerzen z. B. chronische Migräne oder chronischer Spannungskopfschmerz ist weitestgehend unbekannt. Basierend auf der Hypothese, dass inflammatorische Mechanismen an der Genese chronischer Kopfschmerzen beteiligt sind, haben wir in einem tierexperimentellen Modell die Dura mater von Ratten mit IL-1β (10 ng/ml) unilateral stimuliert um biochemische und molekulare Veränderungen in schmerzsensitiven intrakraniellen Geweben zu untersuchen. Die IL-1β-Applikation führt zur Expression von c-fos im ipsilateralen Trigeminuskern nach 3 h, die durch vorherige Gabe von Sumatriptan blockiert werden kann. Die lokale Stimulation mit IL-1β führt zur Inflammation mit COX-2-mRNA und Proteinexpression. Eine repetitive Stimulation führt zu erhöhter COX-2-Expression. Die CGRP-mRNA-Bestimmung im Ganglion trigeminale ergab mittels RT-PCR-Untersuchung keine Änderung der Expression. Zusammengefasst führt die IL-1β-Stimulation zur lokalen meningealen Inflammation und Aktivierung des trigeminalen Schmerzsystems. Die Identifikation weiterer Effekte einer repetitiven meningealen Stimulation kann zur Entdeckung pathophysiologisch relevanter Mechanismen führen, die zur Entstehung chronischer Kopfschmerzen beitragen.

Abstract

The pathophysiology of chronic headaches such as chronic migraine or chronic tension type headache is poorly understood. Based on the assumption that inflammory mechanisms are involved in the pathophysiology of chronic headaches we have used topic stimulation of the rat dura mater with IL-1β (10 ng/ml) to examine changes in headache relevant structures within the brain. IL-1β causes ipsilateral c-fos expression within the trigeminal nucleus caudalis after 3 hours which can be blocked by pre-treatment with sumatriptan. IL-1β induced inflammation comprises of COX-2 impression within the dura as demonstrated by rt-PCR and western blotting. COX-2 expression is more pronounced after repeated (3 days) stimulation. CGRP mRNA levels within trigeminal ganglion were unchanged. In summary, IL-1β stimulation causes local meningal inflammation and activation of the trigeminal nerve system. The investigation of the effects of repetitive meningeal stimulation will possibly identify mechanisms involved in the generation of chronic headaches.

Schlüsselwörter

Migräne - Dura mater - N. trigeminus - Inflammation

Key words

chronic headache - meninges - trigeminal

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