Spinal nerve injury enhances subthreshold membrane potential oscillations in DRG neurons: relation to neuropathic pain

Primary sensory neurons with myelinated axons were examined in vitro in exc ised whole lumbar dorsal root ganglia (DRGs) taken from adult rats up to 9 days after tight ligation and transection of the L-5 spinal nerve (Chung mo del of neuropathic pain). Properties of subthreshold membrane potential osc illations, and of repetitive spike discharge, were examined. About 5% of th e DRG neurons sampled in control DRGs exhibited high-frequency, subthreshol d sinusoidal oscillations in their membrane potential at rest (V-r), and an additional 4.4% developed such oscillations on depolarization. Virtually a ll had noninflected action potentials (A(0) neurons). Amplitude and frequen cy of subthreshold oscillations were voltage sensitive. A(0) neurons with o scillations at V-r appear to constitute a population distinct from A(0) neu rons that oscillate only on depolarization. Axotomy triggered a significant increase in the proportion of neurons exhibiting subthreshold oscillations both at V-r and on depolarization. This change occurred within a narrow ti me window 16-24 h postoperative. Axotomy also shifted the membrane potentia l at which oscillation amplitude was maximal to more negative (hyperpolariz ed) values, and lowered oscillation frequency at any given membrane potenti al. Most neurons that had oscillations at V-r, or that developed them on de polarization, began to fire repetitively when further depolarized. Spikes w ere triggered by the depolarizing phase of oscillatory sinusoids. Neurons t hat did not develop subthreshold oscillations never discharged repetitively and rarely fired more than a single spike or a short burst, on step depola rization. The most prominent spike waveform parameters distinguishing neuro ns capable of generating subthreshold oscillations, and hence repetitive fi ring, was their brief postspike afterhyperpolarization (AHP) and their low single-spike threshold. Neurons that oscillated at V-r tended to have a mor e prolonged spike, with slower rise- and fall-time kinetics, and lower spik e threshold, than cells that oscillated only on depolarization. The main ef fects of axotomy were to increase spike duration, slow rise- and fall-time kinetics, and reduce single-spike threshold. Tactile allodynia following sp inal nerve injury is thought to result from central amplification ("central sensitization") of afferent signals entering the spinal cord from residual intact afferents. The central sensitization, in turn, is thought to be tri ggered and maintained in the Chung model by ectopic firing originating in t he axotomized afferent neurons. Axotomy by spinal nerve injury enhances sub threshold membrane potential oscillations in DRG neurons, augments ectopic discharge, and hence precipitates neuropathic pain.