title: Stimulation of rat cranial dura mater with potassium chloride causes CGRP release into the cerebrospinal fluid and increases medullary blood flow.
abstract: Primary headaches may be accompanied by increased intracranial blood flow induced by the release of the potent vasodilator calcitonin gene-related peptide (CGRP) from activated meningeal afferents. We aimed to record meningeal and medullary blood flow simultaneously and to localize the sites of CGRP release in rodent preparations in vivo and ex vivo. Blood flow in the exposed rat parietal dura mater and the medulla oblongata was recorded by laser Doppler flowmetry, while the dura was stimulated by topical application of 60mM potassium chloride (KCl). Samples of jugular venous plasma and cerebrospinal fluid (CSF) collected from the cisterna magna were analysed for CGRP concentrations using an enzyme immunoassay. In a hemisected rat skull preparation lined with dura mater the CGRP releasing effect of KCl superfusion was examined. Superfusion of the dura mater with KCl decreased meningeal blood flow unless alpha-adrenoceptors were blocked by phentolamine, whereas the medullary blood flow was increased. The same treatment caused increased CGRP concentrations in jugular plasma and CSF and induced significant CGRP release in the hemisected rat skull preparation. Anaesthesia of the trigeminal ganglion by injection of lidocaine reduced increases in medullary blood flow and CGRP concentration in the CSF upon meningeal KCl application. CGRP release evoked by depolarisation of meningeal afferents is accompanied by increased blood flow in the medulla oblongata but not the dura mater. This discrepancy can be explained by the smooth muscle depolarising effect of KCl and the activation of sympathetic vasoconstrictor mechanisms. The medullary blood flow response is most likely mediated by CGRP released from activated central terminals of trigeminal afferents. Increased blood supply of the medulla oblongata and CGRP release into the CSF may also occur in headaches accompanying vigorous activation of meningeal afferents.
authors.affiliation: Department of Physiology, University of Szeged. Dóm tér 10, H-6720 Szeged, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Dux
authors.affiliation: Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Universitätsstrasse 17, D-91054 Erlangen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Will
authors.affiliation: Department of Anaesthesia and Critical Care Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Eberhardt
authors.affiliation: Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Universitätsstrasse 17, D-91054 Erlangen, Germany.
authors.forename: Michael J M
authors.initials: MJM
authors.lastname: Fischer
authors.affiliation: Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Universitätsstrasse 17, D-91054 Erlangen, Germany. Electronic address: karl.messlinger@fau.de.
authors.forename: Karl
authors.initials: K
authors.lastname: Messlinger
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000134:cerebrospinal fluid*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004388:Dura Mater / Q000187:drug effects*; D006261:Headache / Q000503:physiopathology; D008297:Male; D008578:Meninges / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology*; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects*; D012668:Trigeminal Ganglion / Q000187:drug effects
chemical_list: D018015:Receptors, Calcitonin Gene-Related Peptide; D011189:Potassium Chloride; D015740:Calcitonin Gene-Related Peptide
keywords: Headache; Jugular plasma; Laser Doppler flowmetry; Meningeal afferents; Neuropeptides