Peptidergic and serotoninergic innervation of the rat dura mater

Abstract

The peptidergic and serotoninergic innervation of the rat dura mater was investigated by reacting dural wholemounts immunohistochemically with antibodies to calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), and serotonin (5-HT). CGRP and SP innervations of the dura were robust and the patterns of distribution of these neuropeptides were essentially the same. The majority of the fibers were perivascular and distributed to branches of the anterior and middle meningeal arteries and to the superior sagittal and transverse sinuses. Other CGRP/SP fibers appeared to end "free" within the dural connective tissue. NPY-immunoreactive fibers were extremely numerous and also distributed heavily to the branches of the meningeal arteries, the venous sinuses, and to the dural connective tissue. The pattern of NPY innervation resembled in many ways that of CGRP/SP; however, NPY innervation of the sinuses was greater and NPY perivascular fibers supplying the meningeal arteries formed more intimate contacts with the walls of the vessels. The pattern of VIP innervation was, in general, similar to that observed for the three previous neuropeptides; however, the overall density was considerably less. Small to moderate numbers of serotoninergic nerve fibers were observed in some, but not all, of the duras processed for 5-HT. The latter fibers were almost exclusively perivascular in distribution. Dural mast cells were prominently stained in the 5-HT preparations because of their serotonin content. Mast cells were also labeled in a nonspecific fashion in some of the tissues reacted immunohistochemically for neuropeptides; some of them were located in close apposition to passing nerve fibers. This study represents, to our knowledge, the first comprehensive work on the peptidergic and serotoninergic innervation of the mammalian dura mater. The results should increase our understanding of the roles that these fibers play in normal dural physiology and of their potential interactions in the pathogenesis of vascular headache.

Increase of meningeal blood flow after electrical stimulation of rat dura mater encephali: mediation by calcitonin gene‐related peptide

“…Histochemical studies by von During et al (1990) and Keller & Marfurt (1991) as well as our recent investigation (Messlinger et al, 1993) revealed that the dura mater encephali of the rat is densely innervated by both substance P and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibres of small diameter suggesting the presence of these neuropeptides within distinct classes of dural afferents. Whereas substance P (as well as neurokinin A) seems to mediate mainly plasma extravasation that can be inhibited by the NK, receptor antagonist, RP 67580 (Moussaoui et al, 1993;Shepheard et al, 1993), it is suggested that CGRP contributes little to this response (Markowitz et al, 1987).…”

“…Human CGRP itself caused an increase of the basal blood flow without electrical stimulation. Since the dura mater encephali is densely innervated by CGRP immunoreactive nerve fibres (Keller & Marfurt, 1991;Messlinger et al, 1993), it is likely that CGRP-is released from these nerve endings when they are activated by electrical stimulation. The same stimuli probably also release substance P (Edvinsson et al, 1983) that is stored in a smaller proportion of dural nerve fibres (von During et al, 1990;Messlinger et al, 1993) where it may largely be co-localized with CGRP (O'Connor & van der Kooy, 1988), possibly in the same vesicles (Gulbenkian et al, 1986).…”

“…It was suggested that this increase was mediated by vasoactive intestinal polypeptide (VIP) which is co-localized in cholinergic nerve fibres. Since the dura mater also shows a sparse VIPimmunopositive-innervation (Keller & Marfurt, 1991), it is possible that a small part of the increase of blood flow that persisted after the application of h-CGRP837 was induced by VIP.…”

The Nonpeptide Calcitonin Gene-Related Peptide Receptor Antagonist BIBN4096BS Lowers the Activity of Neurons with Meningeal Input in the Rat Spinal Trigeminal Nucleus

“…In peripheral tissues, CGRP released from perivascular afferents contributes to the development and maintenance of neurogenic inflammation Gamse and Saria, 1986). Meningeal (dural and pial) blood vessels are innervated by a dense network of trigeminal sensory fibers, a major proportion of which contains CGRP (Edvinsson et al, 1987;Keller and Marfurt, 1991;Messlinger et al, 1993). CGRP is released on stimulation from both the peripheral and central processes of these trigeminal afferents Jenkins et al, 2004).…”

Release of immunoreactive substance P in the brain stem upon stimulation of the cranial dura mater with low pH – inhibition by the serotonin (5‐HT1) receptor agonist CP 93,129

“…The dura mater encephali is richly innervated by thin a erent nerve ®bres, a minor proportion of which exhibits substance P immunoreactivity (rat: Keller &Marfurt, 1991 andVon DuÈ ring et al, 1990; cat and rat: Messlinger et al, 1993;guinea-pig: Edvinsson et al, 1983). Meningeal a erents originating in the trigeminal ganglion (Mayberg et al, 1984;O'Connor & van der Kooy, 1986;Steiger & Meakin, 1984;Uddman et al, 1989) project mainly to the spinal trigeminal nucleus, where numerous substance P immunoreactive nerve ®bres were found particularly in the substantia gelatinosa (Cuello et al, 1978;Del Fiacco et al, 1983;Pearson & Jennes, 1988;Tashiro et al, 1991).…”