Abstract
In this paper morphological and physiological experiments are described that refer to the concept of neurogenic inflammation of meningeal structures as a putative source of migrainous pain and other headaches. The main emphasis of this study carried out on the duramater encephali of the rat was the functional role of calcitonin generelated peptide (CGRP), a vasodilatory neuropeptide of fine afferent nerve fibres. Immunocytochemical preparations showed that the parietal dura mater was densely innervated by CGRP immunoreactive nerve fibres, the distribution and ultrastructure of which were examined by ligh and electron microscopy. The dense innervation around the medial meningeal artery suggested a vasomotor function of these peptidergic fibres. In further experiments the CGRP immune product of the nerve fibres could be diminished by electrical stimulation of the dura mater. Extracellular recordings from trigeminal ganglion cells showed that electrical and mechanical stimulation of large dural vessels activate trigeminal afferents. In a final series of experiments the dural blood flow around branches of the medial meningeal artery was measured with a laser Doppler flowmeter. The blood flow was increased by electrical stimulation of the dura, the size of this effect depending on stimulus strength and frequency. This increase was inhibited in a dose-dependent manner by the competitive CGRP antagonist CGRP8–37, which shows an involvement of CGRP in the regulation of meningeal blood flow. We conclude that stimulation of trigeminal afferents innervating the dura mater releases CGRP from peptidergic afferent terminals, thereby causing vasodilatation and increasing the meningeal blood flow, an important component of neurogenic inflammation. The preparation decribed will be used for further studies on basic mechanisms of neurogenic inflammation and nociception in meningeal structures.
Zusammenfassung
Die vorliegende Arbeit beschreibt Experimente zur neurogenen Entzündung der Hirnhäute, die als Ursache des Migräneschmerzes und anderer Kopfschmerzformen diskutiert wird. Die Arbeit umfaßt ein Spektrum struktureller und funktioneller Untersuchungen an der Dura mater encephali der Ratte. Im Mittelpunkt steht dabei das “calcitonin gene-related peptide” (CGRP), ein vasodilatorisch wirkendes Neuropeptid afferenter Nervenfasern, das an neurogenen Entzündungsvorgängen maßgeblich beteiligt zu sein scheint. Mit immunzytochemischen Methoden wurde zunächst die Verteilung und die Struktur der CGRP-positiven Nervenfasern in der Dura mater licht- und elektronenmikroskopisch dargestellt. Die dichte CGRP-immunreaktive Innervierung im Stromgebiet der Arteria meningea media deutete auf eine Beteiligung dieser Nervenfasern an vasomotorischen Reaktionen hin. Durch elektrische Stimulierung der Dura mater konnte das sichtbare CGRP-Immunprodukt der Nervenfasern in Abhängigkeit von der Reizdauer vermindert werden. Erste elektrophysiologische Ableitungen aus dem Ganglion trigeminale zeigten, daß durch elektrische und mechanische Stimulierung großer Hirnhautgefäße afferente Fasern des trigeminalen Systems erregt werden können. In einer letzten Experimentfolge wurde mit einem Laser-Doppler-Flowmeter die Durchblutung der Dura mater registriert. Der Blutfluß konnte durch elektrische Stimulierung reizstärken- und frequenzabhängig gesteigert werden. Diese evozierte Blutflußerhöhung wurde dosisabhängig durch den kompetitiven CGRP-Antagonisten CGRP8–37 gehemmt, was die Beteiligung von CGRP an der Steuerung der Hirnhautdurchblutung nahelegt. Die Experimente lassen darauf schließen, daß durch eine Aktivierung trigeminaler Afferenzen der Dura mater das Neuropeptide CGRP aus afferenten Nervenendigungen freigesetzt wird und die Vasodilatation, eine wichtige Komponente der neurogenen Entzündung, verursacht. Das beschriebene Präparat soll zur weiteren Aufklärung neurogener Entzündungsvorgänge und nozizeptiver Mechanismen in den Hirnhäuten verwendet werden.
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Herrn Professor R. F. Schmidt für 20 Jahre Schmerzforschung gewidmet
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Meßlinger, K., Hanesch, U. Calcitonin gene-related peptide immunreaktive Nervenfasern in der Dura mater encephali der Ratte. Schmerz 9, 20–28 (1995). https://doi.org/10.1007/BF02530381
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DOI: https://doi.org/10.1007/BF02530381
Key words
- Dura mater encephali
- Trigeminal afferents
- Peptide release
- CGRP
- Neurogenic inflammation
- Meningeal bloodflow
- Headache