Fig. 1

Activation of trigeminal nerve terminals by PregS in male and female mouse meninges. (A, B) Example traces of multi-unit activity (MUA) in the TG nerve innervating meninges in a hemiskull preparation of male (A) and female(B) mice recorded in the control condition (left), after application 5 μM Yoda1 (middle) and after 50 μM PregS (right). (C) Time course of spike frequency (10-s bin size) induced by application of 50 mM KCl, 5 μM Yoda1, 50 μM PregS and 1 μM capsaicin in males and females (mean ± SEM, n = 5 and n = 7, respectively). Notice the stable recovery of persistence firing during a 20-min washout after each drug application. (D) Histograms show the mean number of nociceptive spikes during 10-min recordings before (control) and after application of 50 μM PregS in males (mean ± SEM, n = 5, p = 0.06, Wilcoxon signed-rank test) and females (mean ± SEM, n = 7, p = 0.01, Wilcoxon signed-rank test). Notice the sex difference in firing when 50 μM PregS was applied (p = 0.0025, Mann–Whitney U test)