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 inflamm ation within the dura mater and cerebral vasodilatation. These process es have been implicated in the pathogenesis of migraine headache. Neur ogenic vasodilator responses to trigeminal ganglion stimulation were i nvestigated in rat facial skin, an area innervated by the trigeminal n erve. Microvascular blood flow changes in the facial skin were measure d in anaesthetised rats, using laser Doppler flowmetry. Electrical sti mulation 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 response s was studied using selective receptor antagonists. The calcitonin gen e-related peptide antagonist, CGRP(8-37) (400 nmol.kg(-1), i.v.) had n o effect on resting levels of facial skin blood flow, but markedly inh ibited responses induced by trigeminal ganglion stimulation (5 Hz, 10 V, 1 ms for 30 s). However, neither the neurokinin-1 (NK1) receptor an tagonist, RP67580 (0.23 or 2.3 mu mol.kg(-1), i.v.) nor the vasoactive intestinal peptide (VIP) antagonist, [p-Cl-D-Phe(6),Leu(17)]-VIP (15 or 30 nmol.kg(-1), i.v.) had any effect on these responses. These resu lts suggest that CGRP is the major neuropeptide involved in the vasodi lator response to trigeminal ganglion stimulation in rat facial skin. Clarification of the mechanisms involved in this neurogenic vasodilato r response may aid the development of drugs that target the trigeminov ascular system during migraine headache.