title: Capsaicin-insensitive sensory-efferent meningeal vasodilatation evoked by electrical stimulation of trigeminal nerve fibres in the rat.
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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University Medical School of Pécs, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Peitl
authors.forename: G
authors.initials: G
authors.lastname: Pethô
authors.forename: R
authors.initials: R
authors.lastname: Pórszász
authors.forename: J
authors.initials: J
authors.lastname: Németh
authors.forename: J
authors.initials: J
authors.lastname: Szolcsányi
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology; D004558:Electric Stimulation; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D017078:Laser-Doppler Flowmetry; D008297:Male; D008578:Meninges / Q000098:blood supply*; D009297:Nasal Mucosa / Q000187:drug effects / Q000294:innervation; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012711:Serum Albumin, Radio-Iodinated; D014276:Trigeminal Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004224:Diterpenes; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D009498:Neurotoxins; D010446:Peptide Fragments; D012711:Serum Albumin, Radio-Iodinated; C058636:calcitonin gene-related peptide (8-37); C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D014660:Vasoactive Intestinal Peptide; C024353:resiniferatoxin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin