Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus-induced thrombus formation, intraneural edema, and reduction of nerve conduction velocity - Possible implications for future pharmacologic treatment strategies of sciatica

Study Design. The possibility to prevent nucleus pulposus-induced functiona l and structural nerve root injury by selective tumor necrosis factor-alpha inhibition was assessed in an experimental model in the pig spine. Objective, The objective of the study was to evaluate the role of tumor nec rosis factor-alpha in the mediation of nucleus pulposus-induced nerve injur y by using selective inhibition. Summary of Background Data. The cytokine tumor necrosis factor-alpha has be en suggested to play a key role in the nerve root injury induced by local a pplication of nucleus pulposus. However, previous studies have not been abl e to distinguish the effects between tumor necrosis factor-a and other disc -related cytokines because of the use of nonspecific cytokine inhibition. Methods. Autologous nucleus pulposus was harvested from a lumbar disc and a pplied to the porcine sacrococcygeal cauda equina. The pigs were simultaneo usly treated with two selective tumor necrosis factor-a inhibitors (etanerc ept n = 8 and infliximab n = 5), a heparin analogue (enoxaparin n = 5) or s aline for control (n = 5), After 7 days the nerve conduction velocity over the application zone was determined and samples of the exposed nerve roots were collected for light microscopic evaluation. Results. The two tumor necrosis factor-alpha inhibitors prevented the reduc tion of nerve conduction velocity and also seemed to limit the nerve fiber injury, the intracapillary thrombus formation, and the intraneural edema fo rmation. However, treatment with enoxaparin did not seem to be different fr om control regarding reduction of nerve conduction velocity or histologic c hanges, Conclusions. The data clearly indicate that tumor necrosis factor-alpha is involved in the basic pathophysiologic events leading to nerve root structu ral and functional changes after local application of nucleus pulposus. The study therefore provides a basic scientific platform with potential clinic al implications regarding the use of antitumor necrosis factor-alpha medica tion as treatment in patients with disc herniation and sciatica.