Neurons with spontaneous high-frequency discharges in the central nervous system and chronic pain

Abstract

Neurons with high-frequency discharge (hyperactive neuron) were recorded in the thalamus of chronic pain patients. We created a chronic pain rat model, and recorded the discharge of high-frequency neurons by using a microelectrode in the thalamic area. The character of these high-frequency discharge neurons was assessed. Deep brain stimulation (DBS) was done in 9 patients, and motor cortical stimulation (MCS) in 2. Prior to implantation of the stimulation electrodes, extracellular unitary activity was recorded and local microstimulation was done by the same microelectrode. From the ventrocaudal (Vc) nucleus of the chronic pain patients, hyperactive neurons were recorded. There were three types of discharge patterns in interval histograms. Some hyperactive neurons showed firing suppression for a short time period by intravenous administration of phenytoin and calcium antagonist (Nicardipine). In animal experiments, unilateral dorsal root sectioning from C5 to Th1 were made in male Wistar rats according to the method of Lombard et al. (1979). A few months after the operation, hyperactive neurons were recorded from the thalamic nuclei and lemniscus medialis. The firing patterns and distribution of hyperactive neurons were very similar to those of humans. Sensorimotor cortical electrical stimulation showed a reduction of firing in the hyperactive neurons. Iontophoretical application of glutamate yielded an increase in firing. In contrast, GABA and NMDA antagonist MK-801 revealed remarkable firing suppression. These results suggest that hyperactive neurons may correlate with the glutamatergic, especially NMDA and GABAergic receptor or fibers.