Capsaicin-insensitive sensory-efferent meningeal vasodilatation evoked by electrical stimulation of trigeminal nerve fibres in the rat.
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.
Peitl
B
B
Department of Pharmacology and Pharmacotherapy, University Medical School of Pécs, Hungary.
Pethô
G
G
Pórszász
R
R
Németh
J
J
Szolcsányi
J
J
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*
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