Effects of vasoactive intestinal peptide on neuroexcitability of female-specific subpopulation of myelinated Ah-type neurons isolated from trigeminal ganglia of adult female rats.

Migraine headache remains a health issue more commonly seen in women with a complicated pathophysiology and is under debate. Vasoactive intestinal peptide (VIP) is a potential factor associated with trigeminovascular system. Here, trigeminal ganglion (TG) neurons were isolated from adult female rats and action potentials (AP) from identified myelinated Ah-type were recorded before and after treatment with VIP with or without blockers using whole-cell patch-clamp technique. The results showed that VIP 100 nM induced a significant increase in the firing frequency of repetitive discharge in these Ah-type TG neurons with dramatic narrowed AP, increased rate of derivative of down-stroke velocity, and deeper after-hyperpolarization (AHP), and these alternations could be reversed by Iberiotoxin except for AHP that was abolished by Apamin. Strikingly, VIP-mediated increase in firing frequency of AP and waveform characters of repolarization were completely blocked by PG97-269, rather that PG-99-465. Interestingly, PG97-269 alone could also slightly but markedly reduced repetitive firing of Ah-type TG neurons under control condition. Taken all these data together, we conclude that VIP upregulates the neuroexcitability of female-specific Ah-type neurons via presumable VPAC1 activation that plays a minor role in the development of basal neuroexcitation and the dataset adds valuable insights into the etiology of migraine headache.