CP‐93,129, sumatriptan, dihydroergotamine block c‐fos expression within rat trigeminal nucleus caudalis caused by chemical stimulation of the meninges

Abstract

1 The effects of intravenously administered 5-HTIB receptor agonists were examined on c-fos-like immunoreactivity, an indicator of neuronal activation, within the brain stem. C-fos was induced by injecting an algesic, vasoconstrictor substance (0.3 ml of autologous blood) or a pro-inflammatory molecule, carrageenin (1 mg in 0.1 ml saline) into the cisterna magna of pentobarbitone-anaesthetized Sprague-Dawley rats and was visualized in serial sections (50gLm) by use of a polyclonal antiserum.2 As previously reported, the injection of blood caused significant labelling within laminae I, II. of the trigeminal nucleus caudalis, a major nociceptive brain stem nucleus, as well as within nucleus of the solitary tract and area postrema. A similar pattern of expression with fewer cells per section was detected after carrageenin instillation. The number of expressing cells was reduced by 54% in trigeminal nucleus caudalis but not within the nucleus of the solitary tract or area postrema when blood was injected in adult rats after neonatal capsaicin treatment.

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

“…CP 93,129 at this dose signi®cantly reduced the neurogenic plasma extravasation in the dura mater encephali of the rat (Matsubara et al, 1991) which is known to depend on the activation of NK-1 receptors by substance P and (possibly) neurokinin A (Markowitz et al, 1987;Buzzi & Moskowitz, 1990). CP 93,129 at this dose also reduced the c-fos expression in the spinal trigeminal nucleus of the rat evoked by injection of autologous blood into the cisterna magna as a noxious stimulus (Nozaki et al, 1992). In the present study there was no enhancement of the release of ir-SP in the medullary brain stem following acidic stimulation after pretreatment with CP 93,129 at this dose.…”

“…An increase in c-fos expression was observed in the spinal trigeminal nucleus following noxious stimulation of the cranial meninges (Cutrer et al, 1995;Kaube et al, 1993;Nozaki et al, 1992). Substance P, which may be released in the trigeminal nucleus upon meningeal stimulation, possibly contributes to these nociceptive responses.…”

“…CP 93,129 has previously been shown to be highly e ective in reducing the substance P-dependent plasma extravasation in the rat dura mater (Matsubara et al, 1991) and the c-fos expression in the spinal trigeminal nucleus (Nozaki et al, 1992).…”

“…There is evidence, however, that they a ect the release of neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) from peripheral endings of trigeminal a erents. 5-HT 1 receptor agonists were shown to inhibit the increase of CGRP concentration in the venous out¯ow from the head both after experimental trigeminal ganglion stimulation and during migraine attacks (Buzzi et al, 1991;Goadsby & Edvinsson, 1993 and to suppress the expression of cfos in the trigeminal brain stem after noxious stimulation of trigeminal structures (Cutrer et al, 1995;Nozaki et al, 1992;Shepheard et al, 1995).…”

Blockade by oral or parenteral RPR 100893 (a non‐peptide NK1 receptor antagonist) of neurogenic plasma protein extravasation within guinea‐pig dura mater and conjunctiva

“…The inhibition of c-fos antigen expression within this brain region was previously demonstrated after giving analgesics such as morphine, or after sumatriptan or dihydroergotamine following noxious meningeal stimulation (Presley et al, 1990;Nozaki et al, 1992;Moskowitz et al, 1993 67580 and RPR 100893 are structural analogues, the possibility that RPR 100893 possesses local anaesthetic-like actions in addition to actions at the NKI receptor cannot now be ruled out. However, the large concentrations of RP 67580 required to achieve non-specific blockade argues in favour of an NKI receptor-mediated mechanism in the studies reported herein.…”