Membrane potential oscillations in dorsal root ganglion neurons: Role in normal electrogenesis and neuropathic pain

Abnormal afferent discharge originating at ectopic sites in injured primary sensory neurons is thought to be an important generator of paraesthesias, dysaesthesias, and chronic neuropathic pain. We report here that the abilit y of these neurons to sustain repetitive discharge depends on intrinsic res onant properties of the cell membrane and that the prevalence of this chara cteristic increases after nerve injury. Recording from primary sensory neur ons in excised rat dorsal root ganglia, we found that some cells show subth reshold oscillations in their membrane potential. The amplitude, frequency, and coherence of these oscillations were voltage sensitive. Oscillations g ave rise to action potentials when they reached threshold. Indeed, the pres ence of oscillations proved to be a necessary condition for sustained spiki ng both at resting membrane potential and on depolarization; neurons withou t them were incapable of sustained discharge even on deep depolarization. P revious nerve injury increased the proportion of neurons sampled that had s ubthreshold oscillations, and hence the proportion that generated ectopic s pike discharge. Oscillatory behavior and ectopic spiking were eliminated by [Na+](o) substitution or bath application of lidocaine or tetrodotoxin (TT X), under conditions that preserved axonal spike propagation. This suggests that a TTX-sensitive Na+ conductance contributes to the oscillations. Sele ctive pharmacological suppression of subthreshold oscillations may offer a means of controlling neuropathic paraesthesias and pain without blocking af ferent nerve conduction.