Calcitonin gene related peptide released from dural nerve fibers mediates increase of meningeal blood flow in the rat

1995 ◽  
Vol 73 (7) ◽  
pp. 1020-1024 ◽  
Author(s):  
K. Meßlinger ◽  
U. Hanesch ◽  
M. Kurosawa ◽  
M. Pawlak ◽  
R. F. Schmidt
Keyword(s):  
Blood Flow ◽  
Dura Mater ◽  
Calcitonin Gene Related Peptide ◽  
Nerve Fibers ◽  
Dura Mater Encephali ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Meningeal Blood Flow ◽  
Meningeal Artery ◽  
Stimulation Of

The parietal dura mater encephali of the rat was shown by immunohistochemistry to be densely innervated by calcitonin gene related peptide (CGRP) immunoreactive nerve fibers spreading around the medial meningeal artery and its branches. Electrical stimulation of the dural surface (10–20 V, 5–10 Hz, 10–30 min) caused a depletion of CGRP-immunopositive fibers, suggesting a release of CGRP. The dural blood flow around branches of the medial meningeal artery was also monitored with a laser Doppler flowmeter. Short periods (30 s) of electrical stimulation with parameters that presumably released CGRP from nerve fibers caused a repeatable and constant increase of the blood flow for 1–2 min. This evoked increase could dose dependently be inhibited by topical application of the CGRP antagonist hCGRP8–37. Accordingly, administration of hCGRP increased the basal 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 element of neurogenic inflammation.Key words: dura mater encephali, afferent nerve fibers, calcitonin gene related peptide, immunohistochemistry, laser Doppler flowmetry.

Increase in Meningeal Blood Flow by Nitric Oxide - Interaction with Calcitonin Gene-Related Peptide Receptor and Prostaglandin Synthesis Inhibition

Cephalalgia ◽  
2002 ◽  
Vol 22 (3) ◽  
pp. 233-241 ◽  
Author(s):  
T Strecker ◽  
M Dux ◽  
K Messlinger
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Dura Mater ◽  
Calcitonin Gene Related Peptide ◽  
Cyclooxygenase Inhibitors ◽  
No Production ◽  
Doppler Flowmetry ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Meningeal Blood Flow

This study addresses possible interactions of the vasodilators nitric oxide (NO), calcitonin gene-related peptide (CGRP) and prostaglandins, which may be implicated in the generation of vascular headaches. Local application of the NO donator diethylamine-NONOate (NONOate) to the exposed dura mater encephali of the rat caused dose-dependent increases in meningeal blood flow recorded by laser Doppler flowmetry. Pre-application of the CGRP receptor antagonist CGRP8-37 significantly attenuated the evoked blood flow increases, while the cyclooxygenase inhibitors acetylsalicylic acid and metamizol were only marginally effective. Stimulation of rat dura mater with NONOate in vitro caused increases in CGRP release. NADPH- diaphorase activity indicating NO production was restricted to the endothelium of dural arterial vessels. We conclude that increases in meningeal blood flow caused by NO depend partly on the release and vasodilatory action of CGRP from dural afferents, while prostaglandins are not significantly involved.

scholarly journals Role Of Cgrp In Sensitization Of Dura Mater

2001 ◽  
Vol 1 ◽  
pp. 20-20
Author(s):  
K. Messlinger
Keyword(s):  
Dura Mater ◽  
Trigeminal Nerve ◽  
Plasma Levels ◽  
Nerve Fibers ◽  
Considerable Proportion ◽  
Trigeminovascular System ◽  
Dura Mater Encephali ◽  
Related Peptide ◽  
Calcitonin Gene

The mammalian dura mater encephali is richly supplied by trigeminal nerve fibers, a considerable proportion of which contains calcitonin gene-related peptide (CGRP). As plasma levels of CGRP are increased in some forms of headaches, the question is in which way CGRP is involved in nociceptive mechanisms within the peripheral and the central trigeminovascular system.

scholarly journals High‐dose phenylephrine increases meningeal blood flow through TRPV1 receptor activation and release of calcitonin gene‐related peptide

2019 ◽  
Vol 24 (2) ◽  
pp. 383-397 ◽  
Author(s):  
Mária Dux ◽  
Alexandru Babes ◽  
Jessica Manchen ◽  
Julika Sertel‐Nakajima ◽  
Birgit Vogler ◽  
...  
Keyword(s):  
Blood Flow ◽  
Receptor Activation ◽  
Calcitonin Gene Related Peptide ◽  
High Dose ◽  
Trpv1 Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Meningeal Blood Flow ◽  
Flow Through

Interaction of Calcitonin Gene-Related Peptide, Nitric Oxide and Histamine Release in Neurogenic Blood Flow and Afferent Activation in The Rat Cranial Dura Mater

Cephalalgia ◽  
2007 ◽  
Vol 27 (6) ◽  
pp. 481-491 ◽  
Author(s):  
N Schwenger ◽  
M Dux ◽  
R de Col ◽  
R Carr ◽  
K Messlinger
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Histamine Release ◽  
Dura Mater ◽  
Calcitonin Gene Related Peptide ◽  
Receptor Blockade ◽  
Cgrp Receptor ◽  
Related Peptide ◽  
Calcitonin Gene

Calcitonin gene-related peptide (CGRP), nitric oxide (NO) and histamine are implicated in primary headaches but their role in vascular and nociceptive events in the dura mater is not well described. In an in vitro preparation of the hemisected rat skull, CGRP and histamine release from the cranial dura was measured using enzyme-linked immunoassays. While the NO donator NONOate (10-4 M) was without effect, CGRP (10-5 M) induced considerable histamine release from the rat cranial dura, which was blocked by the CGRP receptor antagonist CGRP8-37 (10-5 M). Conversely, histamine (10-4 M) did not stimulate CGRP release. In vitro recordings from single rat meningeal afferents showed that only one of 12 mechanically identified units but several mechanically insensitive units responded to histamine (up to 10-5 M). Increases in meningeal blood flow after histamine application (10-4 M) to the rat cranial dura remained unchanged during CGRP receptor blockade with CGRP8-37, inhibition of NO synthesis with L-NAME (20 mg/kg i.v.) and H3 receptor blockade with thioperamide (10-4 M). We conclude that histamine produces direct vasodilatation and activates a subset of largely non-mechanically sensitive, non-CGRP containing afferents in the rat meninges. Histamine is released from meningeal mast cells which are stimulated by CGRP. Similar mechanisms may be involved in the pathogenesis of headaches.

scholarly journals Effects of Neuropeptide Y and Calcitonin Gene-Related Peptide on Local Cerebral Blood Flow in Rat Striatum

1989 ◽  
Vol 9 (3) ◽  
pp. 268-270 ◽  
Author(s):  
Yoshio Suzuki ◽  
Shin-Ichi Satoh ◽  
Ichiro Ikegaki ◽  
Tomohisa Okada ◽  
Masato Shibuya ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Neuropeptide Y ◽  
Calcitonin Gene Related Peptide ◽  
Nerve Fibers ◽  
Rat Striatum ◽  
Local Cerebral Blood Flow ◽  
Related Peptide ◽  
Calcitonin Gene

The effects of neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) on local cerebral blood flow (LCBF) were studied in vivo in rat striatum. Administration of 1 and 5 nmol NPY as a bolus into the internal carotid artery caused a dose-dependent decrease in the ipsilateral striatal LCBF. This decrease developed slowly and persisted for at least 2 h, without affecting mean blood pressure. In contrast, CGRP, at a concentration of 10 pmol, increased striatal LCBF by about 30%, and the duration of the increase was about 1 h. However, at higher doses of CGRP no increase in LCBF was observed. These results suggest that NPY and CGRP released from nerve fibers innervating blood vessels can function as long-acting modulators of CBF.

scholarly journals Inhibition of stimulated meningeal blood flow by a calcitonin gene-related peptide binding mirror-image RNA oligonucleotide

2006 ◽  
Vol 148 (4) ◽  
pp. 536-543 ◽  
Author(s):  
Thomas Denekas ◽  
Markus Tröltzsch ◽  
Axel Vater ◽  
Sven Klussmann ◽  
Karl Messlinger
Keyword(s):  
Blood Flow ◽  
Peptide Binding ◽  
Calcitonin Gene Related Peptide ◽  
Mirror Image ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Meningeal Blood Flow
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