Capsaicin-insensitive sensory-efferent meningeal vasodilatation evoked by electrical stimulation of trigeminal nerve fibres in the rat

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Abstract

1. Antidromic vasodilatation and plasma extravasation to stimulation of the trigeminal ganglion or its perivascular meningeal fibres was investigated by laser-Doppler flowmetry and 125I-labelled bovin serum albumin in the dura mater and in exteroceptive areas (nasal mucosa, upper eyelid) of anaesthetized rats pretreated with guanethidine and pipecuronium. 2. Trigeminal stimulation at 5 Hz for 20 s elicited unilateral phasic vasodilatation in the dura and lasting response in the nasal mucosa. Resiniferatoxin (1-3 μg kg-1 i.v.), topical (1%) or systemic capsaicin pretreatment (300 mg kg-1 s.c. plus 1 mg kg-1 i.v.) did not inhibit the meningeal responses put abolished or strongly inhibited the nasal responses. Administration of vinpocetine (3 mg kg-1 i.v.) increased both basal blood flow and the dural vasodilatation to perivascular nerve stimulation. 3. Dural vasodilatation to trigeminal stimulation was not inhibited by the calcitonin gene-related peptide-1 receptor (CGRP-1) antagonist hCGRP8-37 (15 or 50 μg kg-1 i.v.) or the neurokinin-1 receptor antagonist RP 67580 (0.1 mg kg-1 i.v.) although both antagonists inhibited the nasal response. Neither mucosal nor meningeal responses were inhibited by atropine (5 mg kg-1 i.v.), hexamethonium (10 mg kg-1 i.v.) or the vasoactive intestinal polypeptide (VIP) antagonist (p-chloro-D-Phe6-Leul7) VIP (20 μg kg-1 i.v.). 4. Plasma extravasation in the dura and upper eyelid elicited by electrical stimulation of the trigeminal ganglion was almost completely abolished in rats pretreated with resiniferatoxin (3 μg kg-1 i.v.). 5. It is concluded that in the rat meningeal vasodilatation evoked by stimulation of trigeminal fibres is mediated by capsaicin-insensitive primary afferents, while plasma extravasation in the dura and upper eyelid and the vasodilatation in the nasal mucosa are mediated by capsaicin-sensitive trigeminal fibres.

Original languageEnglish
Pages (from-to)457-467
Number of pages11
JournalBritish journal of pharmacology
Volume127
Issue number2
DOIs
Publication statusPublished - Jun 7 1999

Keywords

  • Capsaicin
  • Dura mater
  • Microcirculation
  • Nasal mucosa
  • Resiniferatoxin
  • Trigeminal ganglion
  • Vasodilatation
  • Vinpocetine
  • hCGRP

ASJC Scopus subject areas

  • Pharmacology

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