Fig. 3

Activation of trigeminal nerve terminals by CIM0216 in male and female mouse meninges. (A, B) Example traces of MUA in TG nerves of male (A) and female (B) mice recorded in the control condition (left), after application 5 μM CIM0216 (middle) and after 1 μM capsaicin (right). (C) Time course of spike frequency induced by application of 50 mM KCl, 5 μM Yoda1, 5 μM CIM0216 and 1 μM capsaicin in males and females (mean ± SEM, 10-s bin size, n = 6 for both sexes). Notice the difference in the 2-min active phase of 5 μM CIM0216 that was much more pronounced in females, and the subsequent silent time in males compared to overactivated firing recovery during the 20-min washout period in females. (D) Histograms show the mean number of nociceptive spikes during 10-min recordings in the control condition and after application of 5 μM CIM0216 in males (mean ± SEM, n = 6, p = 0.03, Wilcoxon signed-rank test) and females (mean ± SEM, n = 6, p = 0.03, Wilcoxon signed-rank test). Notice the sex difference in firing when 5 μM CIM0216 was applied (p = 0.0022, Mann–Whitney U test)