tetrodotoxin and Neuritis

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.

Topics: Afferent Pathways; Animals; Axons; Electric Stimulation; Female; Ganglia, Spinal; Lidocaine; Male; Membrane Potentials; Neural Conduction; Neuritis; Neurons, Afferent; Oscillometry; Pain; Rats; Rats, Wistar; Sodium; Tetrodotoxin

The delayed onset of painful paresthesias following trauma to a peripheral nerve is a well recognized but poorly understood phenomenon. This report describes an illustrative case of painful paresthesias in the territory of the ilioinguinal nerve, 3 to 6 weeks after an otherwise routine herniorraphy, which subsequently responded dramatically to carbamazepine. The case is considered in light of recent studies which have determined molecular changes which occur in dorsal root ganglion (DRG) neurons following axotomy and neuroma formation. Voltage-dependent sodium (Na+) channels in DRG neurons undergo a change following axotomy, in which there is significant up- and down-regulation of different subpopulations of Na channels over a time frame measured in days to weeks. Such changes may render the DRG neurons hyperexcitable, thus contributing to a neuropathic pain syndrome, yet susceptible to treatment with a sodium channel blocker such as carbamazepine.

Topics: Analgesics, Non-Narcotic; Axotomy; Carbamazepine; Ganglia, Spinal; Hernia, Inguinal; Humans; Inguinal Canal; Male; Middle Aged; Neuritis; Neuroma; Pain, Postoperative; Reoperation; Sodium Channels; Tetrodotoxin