Exogenous tumor necrosis factor-alpha 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.

Epidural application of nucleus pulposus enhances nociresponses of rat dorsal horn neurons.

STUDY DESIGN: An electrophysiologic study to examine responses of dorsal horn neurons in the rat L5 spinal cord to noxious stimuli after disc herniation or application of the nucleus pulposus to the L5 nerve root. OBJECTIVES: To investigate the pathogenic role of nucleus pulposus in the neural mechanism underlying sciatica and low back pain. SUMMARY OF BACKGROUND DATA: Application of the nucleus pulposus to the lumbar nerve root induced morphologic, vascular, and functional changes in the nerve root, suggesting that some factors in the nucleus pulposus may be implicated in the pathogenesis of chronic changes. However, it has not been studied whether the epidural application of nucleus pulposus enhances nociresponses of pain-processing neurons in the superficial dorsal horn of the spinal cord. METHODS: Extracellular recordings were made from the L5 dorsal horn neurons in 20 Wistar rats. The wide-dynamic-range (WDR) neurons activated by electric stimulation of the ipsilateral footpad of hindpaw were selected, and their responses to noxious and innocuous stimulation were examined after L5-L6 disc herniation onto the L5 nerve root (Group A) and application of the autologous nucleus pulposus (Group B) or fat tissues (Groups C and D). RESULTS: The herniation of the nucleus pulposus (Group A) and application of the autologous nucleus pulposus (Group B) to the nerve root remarkably enhanced responses of WDR neurons to noxious stimuli for hours, whereas application of fat tissue scarcely enhanced nociresponses (Groups C and D). CONCLUSIONS: Results suggest that somewhat pathogenic factors in the nucleus pulposus may have a crucial role in the induction of hyperalgesia. This may help to elucidate the reason why a severe pain is sometimes induced without a visually identified protrusion.