Papers of the Week

Previously we reported that a group of inflammatory mediators significantly enhanced resurgent currents in dorsal root ganglion (DRG) neurons. To understand the underlying intracellular signaling mechanism, we investigated the effects of inhibition of extracellular signal-regulated kinases (ERK) and protein kinase C (PKC) on the enhancing effects of inflammatory mediators on resurgent currents in rat DRG neurons. We found that the ERK inhibitor U0126 completely prevented the enhancing effects of the inflammatory mediators on both Tetrodotoxin-sensitive (TTX-S) and Tetrodotoxin-resistant (TTX-R) resurgent currents in both small and medium DRG neurons. U0126 substantially reduced repetitive firing in small DRG neurons exposed to inflammatory mediators, consistent with prevention of resurgent current amplitude increases. The PKC inhibitor Bisindolylmaleimide I also showed attenuating effects on resurgent currents, although to a lesser extent compared to ERK inhibition. These results indicate a critical role of ERK signaling in modulating resurgent currents and membrane excitability in DRG neurons treated with inflammatory mediators. It is also suggested that targeting ERK-resurgent currents might be a useful strategy to reduce inflammatory pain.