Trigeminal ganglion stimulation increases facial skin blood flow in the rat: a major role for calcitonin gene-related peptide.
Activation of the trigeminovascular system leads to neurogenic inflammation within the dura mater and cerebral vasodilatation. These processes have been implicated in the pathogenesis of migraine headache. Neurogenic vasodilator responses to trigeminal ganglion stimulation were investigated in rat facial skin, an area innervated by the trigeminal nerve. Microvascular blood flow changes in the facial skin were measured in anaesthetised rats, using laser Doppler flowmetry. Electrical stimulation of the trigeminal ganglion caused an ipsilateral increase in facial skin blood flow which was found to be frequency dependent (0.5-10 Hz). The role of several neuropeptides in these blood flow responses was studied using selective receptor antagonists. The calcitonin gene-related peptide antagonist, CGRP8-37 (400 nmol.kg-1, i.v.) had no effect on resting levels of facial skin blood flow, but markedly inhibited responses induced by trigeminal ganglion stimulation (5 Hz, 10 V, 1 ms for 30 s). However, neither the neurokinin-1 (NK1) receptor antagonist, RP67580 (0.23 or 2.3 mumol.kg-1, i.v.) nor the vasoactive intestinal peptide (VIP) antagonist, [p-Cl-D-Phe6,Leu17]-VIP (15 or 30 nmol.kg-1, i.v.) had any effect on these responses. These results suggest that CGRP is the major neuropeptide involved in the vasodilator response to trigeminal ganglion stimulation in rat facial skin. Clarification of the mechanisms involved in this neurogenic vasodilator response may aid the development of drugs that target the trigeminovascular system during migraine headache.
Escott
K J
KJ
Pharmacology Group and Vascular Biology Research Centre, King's College, London, UK.
Beattie
D T
DT
Connor
H E
HE
Brain
S D
SD
D000818:Animals; D001775:Blood Circulation / Q000502:physiology*; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004558:Electric Stimulation; D005145:Face / Q000098:blood supply*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000098:blood supply*; D013373:Substance P / Q000494:pharmacology*; D012668:Trigeminal Ganglion / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D015740:Calcitonin Gene-Related Peptide