Morphine-3-glucuronide-induced sensory neuron excitation is likely due to effects on voltage-gated sodium channels. (A
B) Representative current traces from acutely dissociated control dorsal root ganglion (DRG) neurons evoked by 200-ms steps in 5-mV increments applied from a holding potential of −100 mV. (C
E) Peak current densities (pA/pF) of DRGs exposed to extracellular recording solution (control) or 3 μM morphine-3-glucuronide (M3G) for 5 minutes. Tetrodotoxin-sensitive (TTX-S) current densities were estimated using a pre-pulse inactivation protocol (500 ms pre-pulses) with a 0 mV test pulse as well as using post hoc kinetic subtraction
. Tetrodotoxin-resistant (TTX-R) current densities were made in the presence of 500 nM TTX to pharmacologically isolate the properties of voltage-gated sodium channel (NaV)1.8 and NaV1.9 currents. TTX-R NaV1.8 currents were estimated from the current elicited from a 150 ms pulse to 0 mV from a holding potential of −100 mV whereas TTX-R NaV1.9 currents were estimated as the current remaining during the last 15 ms of a 150 msec test pulse to −60 mV from a holding potential of −100 mV(*P < 0.05, versus control). Error bars indicate mean ± SE from at least 10 cells per condition. Small- and medium-diameter DRG neurons were used for these experiments.