Tumor Necrosis Factor- Suppresses Sustained Potassium Currents in Rat Small Diameter Sensory Neurons

Tumor necrosis factor(TNF), a pro-inflammatory cytokine, produces pain and hyperalgesia by activating and/or sensitizing nociceptive sensory neurons. In the present study, using whole-cell patch clamp techniques, the regulation of potassium currents by TNFwas examined in acutely dissociated small dorsal root ganglion neurons. We found that acute application of TNFinhibited, in a dose-dependent manner, the non-inactivating sustained potassium current without changing the rapidly inactivating transient current or the voltage-dependence of steady-state inactivation. The effects of TNFon potassium currents were similar to that of prostaglandin E2 as reported previously and also demonstrated in the current study. Furthermore, indomethacin, a potent inhibitor for both cyclo-oxygenase (COX)-1 and COX-2, completely blocked the effect of TNFon potassium currents. These results suggest that TNFmay sensitize or activate sensory neurons by suppressing the sustained potassium current in nociceptive DRG neurons, possibly via stimulating the intracellular production i.e. the synthesis and/or release of endogenous prostaglandins.