Changes in Pain Behavior and Histologic Changes Caused by Application of Tumor Necrosis Factor-Alpha to the Dorsal Root Ganglion in Rats

In Brief Study Design. Histologic changes in the dorsal root ganglion (DRG) and the nociceptive stimulation thresholds were studied in rats. Objective. To examine the effects of tumor necrosis factor-alpha (TNF) with special reference to pain behavior and histology of the DRG. Summary of Background Data. Recently, it was reported that local application of nucleus pulposus induces a characteristic tissue reaction at the surface of the DRG. However, to our knowledge, there have been no previous reports about the relationship between the histologic changes and pain behavior caused by cytokines. Methods. Recombinant TNF was applied to the L4 DRG. Mechanical and thermal nociceptive thresholds were tested. The L4 DRG was sectioned and observed by light microscopy. Results. After the application of 5 ng/μL TNF, significant differences were observed in mechanical and thermal stimulation thresholds. At the site of application of TNF, a characteristic a semilunar-shaped enlargement was observed. The average width of the part was significantly larger in the 5 ng/μL TNF application, as compared to the 0.5-ng/μL TNF application. Conclusions. The higher concentration of TNF used induced allodynia and hyperalgesia responses. Because the region showing the histologic changes was significantly larger after application of the higher concentration of TNF, the reaction of the DRG may be related to pain. Non-noxious mechanical and thermal nociceptive stimulation thresholds were studied in rats after application of tumor necrosis factor-alpha to the dorsal root ganglion. Histologic changes in the dorsal root ganglion, allodynia, and hyperalgesia were observed after application of large amounts of tumor necrosis factor-alpha.