Sevoflurane excites nociceptive sensory neurons by inhibiting K+ conductances in rats

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

“…These findings indicate that sevoflurane is likely to affect the kinetics of inactivation and recovery and that these changes might be sufficient to affect the repetitive activation of the tested channels during sustained membrane depolarization. In line with this speculation, we found that sevoflurane decreased the number of action potentials induced by depolarizing current injection, as shown in our recent study [14]. Such decreases in the number of action potentials might be mediated by the inhibition of I NaP and modulation of both inactivation and recovery kinetics of TTX-R Na + channels.…”

“…In the continued presence of 300 nM TTX, the resting membrane potential of patched neurons was −55.0 ± 2.0 mV (−47.1 to −62.9 mV, n = 8). In these conditions, sevoflurane (0.86 ± 0.02 mM) slightly depolarized membrane potentials (3.3 ± 0.8 mV; n = 8; P < 0.01), which would be due to the sevoflurane inhibition of leak K + conductances [14]. Sevoflurane (0.86 ± 0.02 mM) also decreased the number of action potentials elicited by depolarizing current stimuli (43.2 ± 6.1% of the control; n = 8; P < 0.01, Fig.…”

“…In addition, volatile anesthetics are known to excite nociceptive neurons by the activation of several types of transient receptor potential channels [25,26]. Furthermore, our recent study has also shown that sevoflurane directly excites nociceptive neurons by inhibiting K + conductances mediated by two-pore domain K + channels as well as voltage-gated K + channels [14]. The present results provide another evidence that sevoflurane even at anesthetic concentrations may have hyperalgesic effects by potentiating the TTX-R I Na in nociceptive neurons.…”

“…Sevoflurane was completely dissolved by mild shaking, and solutions containing sevoflurane were subjected to the ‘Y–tube system’ for rapid solution exchange [13] with a perfusion rate of 0.5–0.6 ml/min. The aqueous concentration of sevoflurane was determined using gas chromatography [11,14]. The minimum alveolar concentration (MAC) of sevoflurane for anesthesia is known to be 2.05%, but higher concentrations, for example, up to 4.52%, might be required for tracheal intubation [15].…”