Elsevier

Neuroscience

Volume 89, Issue 3, March 1999, Pages 901-907
Neuroscience

Release of substance P, calcitonin gene-related peptide and prostaglandin E2 from rat dura mater encephali following electrical and chemical stimulation in vitro

https://doi.org/10.1016/S0306-4522(98)00366-2Get rights and content

Abstract

Neurogenic inflammation of the dura, expressed in plasma extravasation and vasodilatation, putatively contributes to different types of headache. A novel in vitro preparation of the fluid-filled skull cavities was developed to measure mediator release from dura mater encephali upon antidromic electrical stimulation of the trigeminal ganglion and after application of a mixture of inflammatory mediators (serotonin, histamine and bradykinin, 10−5 M each, pH 6.1) to the arachnoid side of rat dura. The release of calcitonin gene-related peptide, substance P and prostaglandin E2 from dura mater was measured in 5-min samples of superfusates using enzyme immunoassays. Orthodromic chemical and antidromic electrical stimulation of dural afferents caused significant release of calcitonin gene-related peptide (2.8- and 4.5-fold of baseline). The neuropeptide was found to be increased during the 5-min stimulation period and returned to baseline (20.9±12 pg/ml) in the sampling period after stimulation. In contrast, release of substance P remained at baseline levels (19.3±11 pg/ml) throughout the experiment. Prostaglandin E2 release was elevated during chemical and significantly also after antidromic electrial stimulation (6- and 4.2-fold of baseline, which was 305±250 pg/ml). Prostaglandin E2 release outlasted the stimulation period for at least another 5 min.

The data support the hypothesis of neurogenic inflammation being involved in headaches and provide new evidence for prostaglandin E2 possibly facilitating meningeal nociceptor excitation and, hence, pain.

Section snippets

Preparation

Male Wistar rats (400–550 g; raised at the University of Erlangen) were killed in a CO2 atmosphere. The head was separated from the body in the atlanto-occipital joint. The skin and galea were cut along the midline and retracted from the skull, which was then divided into halves by a clear cut along the sagittal suture using a fine saw. The superior sagittal sinus was cut by this preparation. The two hemispheres were removed without lesioning the trigeminal ganglia and the dura mater encephali,

Substance P

Neither electrical stimulation (40 V, 0.5 ms, 10 Hz) nor chemical stimulation with IMs enhanced the release of SP from the dura mater (Fig. 1). The basal release of SP (19.3±11 pg/ml) was measured as lying close to the detection level of the assay (10 pg/ml).

Calcitonin gene-related peptide

CGRP release from the dura mater was massively enhanced by electrical and chemical stimulations (4.5- and 2.8-fold of baseline; see Fig. 2). There was no significant difference in CGRP release between the two concentrations of inflammatory

Stimulation parameters

The dura was antidromically stimulated by electrical stimulation to the trigeminal ganglion at a stimulus strength supposed to elicit action potentials in Aδ- and C-fibers. Aβ-fibers, which would have been excited by the chosen stimulus parameters, have not yet been described in the meninges.[41]Stimulation of the trigeminal ganglion with these electrical parameters has been shown to cause intense plasma extravasation, vasodilatation, degranulation of perivascular mast cells, endothelial

Acknowledgements

We thank M. Dürrbeck and I. Izydorczyk for excellent technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (SFB 353, B12, Z2 and B3).

References (62)

  • M Ringkamp et al.

    Activated human platelets in plasma excite nociceptors in rat skin, in vitro

    Neurosci. Lett.

    (1994)
  • A.S Zagami et al.

    Stimulation of the superior sagittal sinus in the cat causes release of vasoactive petides

    Neuropeptides

    (1990)
  • B Averbeck et al.

    Calcitonin gene-related peptide, substance P and prostaglandin E2 release from rat skin, in vitro, upon stimulation with inflammatory mediators

    Eur. J. Physiol.

    (1997)
  • B Averbeck et al.

    Limits in neurogenic mediation of prostaglandin release in the rat skin in vitro

    Soc. Neurosci. Abstr.

    (1997)
  • M.J Berridge

    Inositol triphosphate and calcium signalling

    Nature

    (1993)
  • S.D Brain et al.

    Substance P regulates the vasodilator activity of calcitonin gene-related peptide

    Nature

    (1988)
  • S.D Brain et al.

    Calcitonin gene-related peptide is a potent vasodilator

    Nature

    (1985)
  • M.G Buzzi et al.

    The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater

    Br. J. Pharmac.

    (1990)
  • M.G Buzzi et al.

    Indomethacin and acetylsalicylic acid block neurogenic plasma protein extravasation in rat dura mater

    Eur. J. Pharmac.

    (1989)
  • J Carmody et al.

    Lack of a role of substance P in the control of dural arterial flow

    Expl Brain Res.

    (1996)
  • V Dimitriadou et al.

    Trigeminal sensory fiber stimulation induces morphological changes reflecting secretion in rat dura mater mast cells

    Neuroscience

    (1991)
  • M.von Düring et al.

    Neuropeptide Y- and substance P-like immunoreactive nerve fibers in the rat dura mater encephali

    Anat. Embryol.

    (1990)
  • A Ebersberger et al.

    Recordings from brain stem neurons responding to chemical stimulation of the subarachnoid space

    J. Neurophysiol.

    (1997)
  • L Edvinsson et al.

    Calcitonin gene-related peptide and cerebral blood vessels: distribution and vasomotor effects

    J. cerebr. Blood Flow Metab.

    (1987)
  • L Edvinsson et al.

    Neuropeptides in migraine and cluster headache

    Cephalalgia

    (1994)
  • L Edvinsson et al.

    Adrenergic, cholinergic and peptidergic nerve fibres in dura mater—involvement in headache?

    Cephalalgia

    (1981)
  • L Edvinsson et al.

    Substance P: localization, concentration and release in cerebral arteries, choroid plexus and dura mater

    Cell Tiss. Res.

    (1983)
  • M Fanciullacci et al.

    Low pH medium induces calcium dependent release of CGRP from sensory nerves of guinea-pig dural venous sinuses

    Life Sci.

    (1991)
  • P.J Goadsby et al.

    The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats

    Ann. Neurol.

    (1993)
  • P.J Goadsby et al.

    Peripheral and central trigeminovascular activation in cats is blocked by the serotonin (5-HT)-1D receptor agonist 311C90

    Headache

    (1994)
  • P.J Goadsby et al.

    Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system

    Ann. Neurol.

    (1988)

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