Intervertebral disc degenerative changes after intradiscal injection of TNF-α in a porcine model

To investigate whether exogenous tumor necrosis factor-alpha (TNF-alpha) will initiate a degenerative process in intervertebral disc in vivo. Exogenous TNF-alpha in dosages of 50 and 100 ng in 50 mu L Dulbecco's Modified Essential Medium (DMEM) was injected into porcine lumbar discs; a third disc was injected only with 50 mu L DMEM as a control. Magnetic resonance imaging (MRI) yielding T1- and T2-weighted images, T2-mapping, and post-contrast T1 images was performed and histology was studied as well. After 3 months, a significant decrease in T2 value calculated from T2-mapping MRI was observed in the annulus and nucleus of both groups injected with TNF-alpha along with a slight decrease in disc height and nucleus volumes in comparison to the control discs. No obvious visual differences among the groups were observed in the normal T1- and T2-weighted MRI images. Post-contrast T1 MRI showed increased annulus enhancement in both TNF-alpha-injected groups compared to the control discs, while no enhancement difference was observed in the nucleus. Histological analysis showed degenerative changes with annulus fissure, cell cluster, nucleus matrix loss, vascularization and interleukin-1 beta expression in the outer annulus of both TNF-alpha-injected discs, while no degenerative changes were observed in the control discs. Intradiscal injection of exogenous TNF-alpha caused early stage disc degeneration in a porcine model. It may thus support the hypothesis of exogenic TNF-alpha being an important early pathogenetic factor in disc degeneration.