Exogenous tumor necrosis factor-α induces abnormal discharges in rat dorsal horn neurons

Study Design. An electrophysiologic study to examine effects of exogenous application of tumor necrosis factor-alpha (TNF-alpha) activities and nociresponses of dorsal horn neurons in the spinal cord at L5. Objectives. To investigate the, role of TNF-alpha in the induction and development of hyperalgesia in neural mechanisms responsible for a radicular pain. Summary of Background Data. TNF-alpha is found in the herniated disc and known to play a pivotal role in the development of inflammatory hyperalgesia; however, it is not known whether TNF-alpha causes abnormal discharge in the dorsal horn neurons and enhances nociresponse. Methods. Single-unit activities of neurons in the L5 superficial dorsal horn were extracellularly recorded, using 28 urethane-anesthetized rats. The wide dynamic range and nociceptive-specific neurons activated by stimulation of the hind paw were selected. Effects of exogenous TNF-alpha were examined regarding 1) spontaneous discharges of wide dynamic range and nociceptive-specific neurons, 2) responses of wide,dynamic range neurons to noxious stimulation, and 3) morphologic changes in the dorsal root ganglion. Results. Application of TNF-alpha to the nerve root induced 1) a significant increase in spikes/sec in spontaneous discharges of wide dynamic range and nociceptive-specific neurons, 2) enhanced responses of wide dynamic range neurons to noxious stimulation, and 3) inflammatory changes in the ganglion. Conclusion. These results suggest the possibility that TNF-alpha produced in, the vicinity of nerve roots due to disc herniation might cause ectopic discharges in primary afferent fibers and thereby induce the prolonged excitation in pain-processing neurons responsible for radicular pain.