Effects of Nucleus Pulposus on Nerve Root Neural Activity, Mechanosensitivity, Axonal Morphology, and Sodium Channel Expression

Abstract

This study analyzed the effects of autografted nucleus pulposus on nerve root axon morphology, neurophysiologic function, and sodium channel expression. To investigate the chronic effects of the epidural implantation of nucleus pulposus on nerve root morphology, neural activity, ectopic discharge, mechanosensitivity, and sodium channel expression. It has been reported that ectopic discharges were recorded antidromically from sural nerve on compressing nucleus pulposus exposed spinal nerves. However, it is not clear what the effects of nucleus pulposus are on ectopic discharges recorded directly from the spinal nerve roots. It is also not clear what the effects of nucleus pulposus are on the threshold pressure to provoke ectopic discharges in the spinal nerves. Sodium channel content increases in remodeling axons after nerve injury, but it is not clear what the effects of nucleus pulposus are on sodium channel expression in spinal nerve. Forty-six male Sprague-Dawley rats were used, 20 in a nucleus pulposus-implanted group, 18 in a fat-implanted group, and 8 in a normal group. Fresh autografted nucleus pulposus or fat tissue was implanted into the dorsal epidural space at the L4-L5 disc level. On the 7th, 21st, or 42nd day, neurophysiologic recordings were made to determine nerve root response to compression. Nerve roots were then harvested to determine sodium channel protein concentration and histologic changes in the nerve root. The correlations between sodium channel density and neural activity and mechanosensitivity of dorsal root were analyzed statistically. Ectopic discharge rate was higher in nucleus pulposus 7-day group. Threshold pressure to evoke ectopic discharges was lower in the nucleus pulposus 7-day group, and higher in the nucleus pulposus 42-day group compared to the normal group. Sodium channel protein density increased in the nucleus pulposus 7-day and nucleus pulposus 21-day group compared to normal nerve. Sodium channel density changes were not correlated to threshold pressure. Ectopic discharge rate increased with increase of sodium channel density in the nerve roots. The number of axons with neuropathy increased in the nucleus pulposus 7-day and 21-day groups. Acute exposure of nerve root to nucleus pulposus resulted in increased number of axons with neuropathy, higher intensity of ectopic discharges on compression, and nerve mechanosensitization. Chronic exposure resulted in mechanical desensitization. Changes of sodium channel density were correlated to ectopic discharge rate.