Nuclear factor-kappa B decoy suppresses nerve injury and improves mechanical allodynia and thermal hyperalgesia in a rat lumbar disc herniation model

Abstract

Nuclear factor-kappa B (NF-jB) is a gene transcriptional regulator of inflammatory cytokines. We investigated the transduction efficiency of NF-jB decoy to dorsal root ganglion (DRG), as well as the decrease in nerve injury, mechanical allodynia, and thermal hyperalgesia in a rat lumbar disc herniation model. Forty rats were used in this study. NF-jB decoy-fluorescein isothiocyanate (FITC) was injected intrathecally at the L5 level in five rats, and its transduction efficiency into DRG measured. In another 30 rats, mechanical pressure was placed on the DRG at the L5 level and nucleus pulposus harvested from the rat coccygeal disc was transplanted on the DRG. Rats were classified into three groups of ten animals each: a herniation ? decoy group, a herniation ? oligo group, and a herniation only group. For behavioral testing, mechanical allodynia and thermal hyperalgesia were evaluated. In 15 of the herniation rats, their left L5 DRGs were resected, and the expression of activating transcription factor 3 (ATF-3) and calcitonin gene-related peptide (CGRP) was evaluated immunohistochemically compared to five controls. The total transduction efficiency of NF-jB decoy-FITC in DRG neurons was 10.8% in vivo. The expression of CGRP and ATF-3 was significantly lower in the herniation ? decoy group than in the other herniation groups.Mechanical allodynia and thermal hyperalgesia were significantly suppressed in the herniation ? decoy group. NFjB decoy was transduced into DRGs in vivo. NF-jB decoy may be useful as a target for clarifying the mechanism of sciatica caused by lumbar disc herniation.

Advancing the cellular and molecular therapy for intervertebral disc disease

“…In a rat lumbar degenerative disc model, IκB kinase β inhibition suppressed the production of calcitonin gene related peptide, a pain-related neuropeptide, suggesting potential reduction of discogenic pain [148]. Similarly, antibodies against IL-1 or TNF-α or NF-κB decoy were able to reduce pain behaviour in animal models [149,150].…”

Inflammatory and catabolic signalling in intervertebral discs: The roles of NF-B and MAP Kinases

“…This strategy reduced nerve injury, improved mechanical allodynia and thermal hyperalgesia in this animal model (Suzuki et al, 2009) and may thus be a promising new approach but one that will require more detailed investigations in the future. A recent study revealed that systemic inhibition of NF-κB activation by the inducible IKK via chronic administration of the Nemo Binding Domain peptide inhibitor, 8K-NBD, in a mouse model of progeria (Ercc1 -/∆ mice) delayed the onset of age-related IDD (Fig.…”

Evaluation of behavior and neuropeptide markers of pain in a simple, sciatic nerve-pinch pain model in rats

“…We demonstrated that nerve injury produces mechanical allodynia and thermal hyperalgesia, and NF-jB decoy was transduced into nuclei of DRG neurons in vivo leading to a decrease of mechanical allodynia and thermal hyperalgesia in rats [25]. On the other hand, we demonstrated that nerve injury caused by lumbar disc herniation produces pain-related behavior, and that a specific p38 inhibitor decreased mechanical allodynia and thermal hyperalgesia in rats [12].…”