Sevoflurane modulation of tetrodotoxin-resistant Na+ channels in small-sized dorsal root ganglion neurons of rats

Objective Volatile anesthetics are widely used for general anesthesia during surgical operations. Voltage-gated Na+ channels expressed in central neurons are major targets for volatile anesthetics; but it is unclear whether these drugs modulate native tetrodotoxin-resistant (TTX-R) Na+ channels, which are involved in the development and maintenance of inflammatory pain. Methods In this study, we examined the effects of sevoflurane on TTX-R Na+ currents (I-Na) in acutely isolated rat dorsal root ganglion neurons, using a whole-cell patch-clamp technique. Results Sevoflurane slightly potentiated the peak amplitude of transient TTX-R I-Na but more potently inhibited slow voltage-ramp-induced persistent I-Na in a concentration-dependent manner. Sevoflurane (0.86 +/- 0.02 mM) (1) slightly shifted the steady-state fast inactivation relationship to hyperpolarizing ranges without affecting the voltage-activation relationship, (2) reduced the extent of use-dependent inhibition of Na+ channels, (3) accelerated the onset of inactivation and (4) delayed the recovery from inactivation of TTX-R Na+ channels. Thus, sevoflurane has diverse effects on TTX-R Na+ channels expressed in nociceptive neurons. Conclusions The present results suggest that the inhibition of persistent I-Na and the modulation of the voltage dependence and inactivation might be, at least in part, responsible for the analgesic effects elicited by sevoflurane.