JOURNAL ARTICLE

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

R Amir, M Michaelis, M Devor
Journal of Neuroscience 1999 October 1, 19 (19): 8589-96
10493758
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 ability of these neurons to sustain repetitive discharge depends on intrinsic resonant properties of the cell membrane and that the prevalence of this characteristic increases after nerve injury. Recording from primary sensory neurons in excised rat dorsal root ganglia, we found that some cells show subthreshold oscillations in their membrane potential. The amplitude, frequency, and coherence of these oscillations were voltage sensitive. Oscillations gave rise to action potentials when they reached threshold. Indeed, the presence of oscillations proved to be a necessary condition for sustained spiking both at resting membrane potential and on depolarization; neurons without them were incapable of sustained discharge even on deep depolarization. Previous nerve injury increased the proportion of neurons sampled that had subthreshold oscillations, and hence the proportion that generated ectopic spike discharge. Oscillatory behavior and ectopic spiking were eliminated by [Na(+)](o) substitution or bath application of lidocaine or tetrodotoxin (TTX), under conditions that preserved axonal spike propagation. This suggests that a TTX-sensitive Na(+) conductance contributes to the oscillations. Selective pharmacological suppression of subthreshold oscillations may offer a means of controlling neuropathic paraesthesias and pain without blocking afferent nerve conduction.

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