1. Inhibiting IκB kinase-β downregulates inflammatory cytokines in injured discs and neuropeptides in dorsal root ganglia innervating injured discs in rats
- Author
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Yoshihiro Sakuma, Sayako Kobori, Toshihide Yamada, Seiji Ohtori, Kazuhisa Takahashi, Miyako Suzuki, Takefumi Gemba, Yasuchika Aoki, Masayuki Miyagi, Gen Inoue, Tomoaki Toyone, Takatoshi Hishiya, Yawara Eguchi, Hiroto Kamoda, Sumihisa Orita, Yasuhiro Oikawa, Gen Arai, and Tetsuhiro Ishikawa
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Calcitonin Gene-Related Peptide ,Interleukin-1beta ,Neuropeptide ,Down-Regulation ,IκB kinase ,Proinflammatory cytokine ,Rats, Sprague-Dawley ,Internal medicine ,Ganglia, Spinal ,Medicine ,Animals ,Orthopedics and Sports Medicine ,Enzyme Inhibitors ,Intervertebral Disc ,Saline ,Neurons ,Lumbar Vertebrae ,business.industry ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Neuropeptides ,Interleukin ,Immunohistochemistry ,I-kappa B Kinase ,Endocrinology ,Cytokine ,Calcitonin ,Cytokines ,Tumor necrosis factor alpha ,Neurology (clinical) ,Inflammation Mediators ,business - Abstract
STUDY DESIGN Quantitative and immunohistological analysis of the efficacy of an IκB kinase-β (IKKβ) inhibitor in an injured intervertebral disc (IVD) model. OBJECTIVE To elucidate the efficacy of an IKKβ inhibitor on inflammatory cytokine levels in injured IVDs or on neuropeptide levels in the dorsal root ganglia (DRG) neurons innervating injured IVDs in rats. SUMMARY OF BACKGROUND DATA Multiple studies have suggested that upregulation of inflammatory cytokines in damaged IVDs causes discogenic low back pain. The efficacy of blocking individual inflammatory cytokines is limited; however, inflammatory cytokine stimuli often require IKKβ to activate nuclear factor-k B. METHODS Sprague-Dawley rats were divided into 3 groups: sham, saline (disc-injury plus saline), and IKKβ (disc-injury plus anti-IKKβ). To induce injury, IVDs were repeatedly punctured.Experiment 1: Four, 7, and 14 days postinjury, coccygeal (Co) 5/6, Co6/7, and Co7/8 IVDs were resected and tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels were quantified by enzyme-linked immunosorbent assay. Experiment 2: The neurotracer Fluoro-Gold was injected into injured L5-L6 IVDs and uninjured sham group IVDs to detect DRG neurons. One week postsurgery, L1-L6 DRGs were immunolabeled with the neuropeptide calcitonin gene-related peptide. The proportions of Fluoro-Gold-labeled calcitonin gene-related peptide-immunoreactive DRG neurons were assessed. RESULTS Experiment 1: IVD levels of tumor necrosis factor-α (through 2 wk), IL-1β (at 4 d), and IL-6 (at 4 d) were significantly higher in the saline group than in the sham group, and significantly lower in the IKKβ group than in the saline group (P < 0.05). Experiment 2: The percentage of calcitonin gene-related peptide-immunoreactive Fluoro-Gold-labeled DRG neurons was significantly higher in the saline group than in the sham group, and significantly lower in the IKKβ group than in the saline group (P < 0.05). CONCLUSION Injury-induced upregulation of inflammatory cytokines within IVDs and increased levels of neuropeptides within DRG neurons can be suppressed by inhibiting IKKβ. LEVEL OF EVIDENCE N/A.
- Published
- 2014