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

Br J Pharmacol. 1999 May;127(2):457-67. doi: 10.1038/sj.bjp.0702561.

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 microg 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 but 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 microg 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 microg 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 microg 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / pharmacology
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Capsaicin / pharmacology*
  • Diterpenes / pharmacology
  • Electric Stimulation
  • Indoles / pharmacology
  • Isoindoles
  • Laser-Doppler Flowmetry
  • Male
  • Meninges / blood supply*
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / innervation
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology*
  • Neurokinin-1 Receptor Antagonists
  • Neurons, Afferent / drug effects*
  • Neurotoxins / pharmacology
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Wistar
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Serum Albumin, Radio-Iodinated
  • Trigeminal Nerve / cytology
  • Trigeminal Nerve / drug effects
  • Trigeminal Nerve / physiology*
  • Vasoactive Intestinal Peptide / analogs & derivatives
  • Vasoactive Intestinal Peptide / pharmacology
  • Vasodilation / drug effects
  • Vasodilation / physiology*

Substances

  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Diterpenes
  • Indoles
  • Isoindoles
  • Neurokinin-1 Receptor Antagonists
  • Neurotoxins
  • Peptide Fragments
  • Serum Albumin, Radio-Iodinated
  • calcitonin gene-related peptide (8-37)
  • 7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one
  • Vasoactive Intestinal Peptide
  • resiniferatoxin
  • Calcitonin Gene-Related Peptide
  • Capsaicin