Fig 6. PF-05198007 acts peripherally and centrally to influence neurotransmitter release.

A. Upper: representative evoked EPSCs during control (blue) and after 30 mins PF-05198007 application (red). Lower: representative synaptically evoked action potential trace (blue) recorded in SG neurons of the dorsal horn following dorsal root stimulation. PF-05198007 (20 mins) abolished synaptically evoked action potentials (red). B. Example time course of EPSC block following PF-05198007 application to the whole preparation. C. Action potentials induced via current injection steps in SG neurons were not abolished by PF-05198007 (30 nM). Representative voltage traces are shown following current injection steps of -20, 0 and 50 pA before (blue traces) and after (red traces) PF-05198007 application. Line chart shows change in firing frequency (Hz) during control and after application of PF-05198007 for all neurons tested (n = 5, p > 0.05, paired t-test). D. Example time course of EPSC block following PF-05198007 application to the dorsal root alone. E. Representative EPSC traces and summary bar graph showing that the application of PF-05198007 (30 nM) to the dorsal root alone inhibited C-fibre mediated EPSCs and resulted in a significant conduction delay (n = 7, * p < 0.05; ANOVA on Ranks). F. PF-05198007 (30 nM; n = 15: 100 nM; n = 19) reduced veratridine evoked CGRP release in spinal cord synaptosomes. Reduction was compared with mexilitine (100 μM; n = 19), Ca²⁺ free conditions (n = 8) and TTX (500 nM; n = 6) (Data are shown ±SEM; * p < 0.05; ANOVA on Ranks).