[Calcitonin gene-related peptide immunoreactive nerve fibres in the dura mater encephali of the rat: experiments related to the neurogenic inflammation of meningeal structures.].

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 CGRP(8-37), 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.