NF-κB DECOY OLIGODEOXYNUCLEOTIDE PRESERVES DISC HEIGHT IN A RABBIT ANULAR-PUNCTURE MODEL AND REDUCES PAIN INDUCTION IN A RAT XENOGRAFT-RADICULOPATHY MODEL

While it is known that the degenerated intervertebral disc (IVD) is one of the primary reasons for low-back pain and subsequent need for medical care, there are currently no established effective methods for direct treatment. Nuclear factor-kappa B (NF-kappa B) is a transcription factor that regulates various genes' expression, among which are inflammatory cytokines, in many tissues including the IVD. NF-kappa B decoy is an oligodeoxynucleotide containing the NF-kappa B binding site that entraps NF-kappa B subunits, resulting in suppression of NF-kappa B activity. In the present preclinical study, NF-kappa B decoy was injected into degenerated IVDs using the rabbit anularpuncture model. In terms of distribution, NF-kappa B decoy persisted in the IVDs up to at least 4 weeks after injection. The remaining amount of NF-kappa B decoy indicated that it fit a double-exponential-decay equation. Investigation of puncture-caused degeneration of IVDs showed that NF-kappa B decoy injection recovered, dose-dependently, the reduced disc height that was associated with reparative cell cloning and morphological changes, as assessed through histology. Gene expression, by quantitative real-time polymerase chain reaction (qRT-PCR), showed that NF-kappa B decoy attenuated inflammatory gene expression, such as that of interleukin-1 and tumor necrosis factor-alpha, in rabbit degenerated IVDs. NF-kappa B decoy also reduced the pain response as seen using the pain sensor nude rat xenograft-radiculopathy model. This is the first report demonstrating that NF-kappa B decoy suppresses the inflammatory response in degenerated IVDs and restores IVD disc height loss. Therefore, the intradiscal injection of NF-kappa B decoy may have the potential as an effective therapeutic strategy for discogenic pain associated with degenerated IVDs.

Automated summary

NF-kappa B decoy injection shows potential as an effective therapeutic strategy for discogenic pain associated with degenerated intervertebral discs, as it suppresses inflammatory responses and restores disc height loss.