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Capsaicin-sensitive neurogenic sensory vasodilatation in the dura mater of the rat
Ist Teil von
The Journal of physiology, 2003-11, Vol.552 (3), p.859-867
Ort / Verlag
Oxford, UK: The Physiological Society
Erscheinungsjahr
2003
Quelle
Wiley-Blackwell Journals
Beschreibungen/Notizen
The neurogenic sensory vascular responses of the dura mater encephali are considered to contribute significantly to the mechanisms
of meningeal nociception and headache. Although the fundamental role of capsaicin-sensitive afferent nerves in the development
of the neurogenic inflammatory responses of a variety of tissues is well established, their participation in meningeal vascular
reactions is unclear. In the present study, the effects of the topical application of capsaicin on the dural blood flow and
on the morphology of the dural nerve fibres were examined in control and capsaicin-pretreated rats by means of laser Doppler
flowmetry and electron microscopy, respectively. In the control rats, the dural application of capsaicin at concentrations
of 50 and 100 n m induced significant increases in blood flow in the branches of the medial meningeal artery. This capsaicin-induced vasodilatation
was abolished by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) receptor antagonist, and by hCGRP 8â37 , a calcitonin gene-related peptide (CGRP) receptor antagonist. Administration of capsaicin at higher concentrations (1 and
10 μ m ) resulted in marked, dose-dependent decreases in dural blood flow. The capsaicin-induced vasodilatation was abolished, whereas
vasoconstriction was augmented, by systemic pretreatment of the animals with capsaicin. Electron microscopy revealed degenerating
unmyelinated axons in the dura mater after an acute exposure to capsaicin (10 μ m ), providing support for the existence and possible functional role of capsaicin-sensitive dural afferent nerves. The results
indicate that capsaicin-induced vasodilatation in the rat dura mater is mediated by the release of CGRP from the sensory nerves,
whereas the vasoconstrictor response may be attributed to a direct action of capsaicin on the vascular smooth muscle. The
present study demonstrates for the first time that capsaicin-sensitive nociceptive afferent nerves contribute significantly
to the dural vasodilatory responses and suggests an important role in meningeal nociception.