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 b y laser-Doppler flowmetry and I-125-labelled bovin serum albumin in the dur a mater and in exteroceptive areas (nasal mucosa, upper eyelid) of anaesthe tized rats pretreated with guanethidine and pipecuronium. 2 Trigeminal stimulation at 5 Hz for 20 s elicited unilateral phasic vasodi latation in the dura and lasting response in the nasal mucosa. Resiniferato xin (1-3 mu g 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 r esponses but abolished or strongly inhibited the nasal responses. Administr ation 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 c alcitonin gene-related peptide-1 receptor (CGRP-1) antagonist hCGRP(8-37) ( 15 Or 50 mu g kg(-1) i.v). or the neurokinin-l receptor antagonist RP 67580 (0.1 mg kg(-1) i.v.) although both antagonists inhibited the nasal respons e. 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 intestin al polypeptide (VIP) antagonist (p-chloro-D-Phe(6)-leu1(7))VIP (20 mu g 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 r ats pretreated with resiniferatoxin (3 mu g kg(-1) i.v.). 5 It is concluded that in the rat meningeal vasodilatation evoked by stimul ation of trigeminal fibres is mediated by capsaicin-insensitive primary aff erents, while plasma extravasation in the dura and upper eyelid and the vas odilatation in the nasal mucosa are mediated by capsaicin-sensitive trigemi nal fibres.