Abstract
Background: Lumbar intervertebral disc (IVD) herniation causes severe low back pain (LBP), which results in substantial financial and emotional strains. Despite the effectiveness of discectomy, there is no existing treatment for post-operative LBP induced by progressive IVD degeneration. Two key factors of LBP are intradiscal inflammation, indicated by tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and sensory nerve ingrowth into the inner layer of the annulus fibrosus, triggered by nerve growth factor/high-affinity tyrosine kinase A (TrkA) signalling. In an animal models of discectomy, the bioresorbable ultra-purified alginate (UPAL) gel with an extremely low-toxicity has been effective in acellular tissue repair. Methods: We aimed to investigate whether UPAL gel can alleviate LBP using a rat nucleus pulposus (NP) punch model and a rabbit NP aspirate model. In both models, we assessed TNF-α and IL-6 production and TrkA expression within the IVD by immunohistochemistry. Further, histological analysis and behavioural nociception assay were conducted in the rat model. Findings: UPAL gel implantation suppressed TNF-α and IL-6 production, downregulated TrkA expression, inhibited IVD degeneration, and reduced nociceptive behaviour. Interpretation: Our results suggest the potential of UPAL gel implantation as an innovative treatment for IVD herniation by reducing LBP and preventing IVD degeneration after discectomy. Funding Statement: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Akiyama Life Science Foundation, Mochida Pharmaceutical Co., Ltd., and Takeda Science Foundation. Declaration of Interests: The authors declare that no competing interests exist. Ethics Approval Statement: All animal procedures were performed in accordance with the ARRIVE guideline and National Institutes of Health guide for the care and use of Laboratory animals, and the study was approved by the Institutional Animal Care and Use Committee of Hokkaido University (17-0122).
Highlights
Lumbar intervertebral disc (IVD) herniation causes severe low back pain (LBP), which results in substantial financial and emotional strains
This study aimed to assess whether ultra-purified alginate (UPAL) gel implantation reduces inflammatory cytokine levels, prevents intervertebral disc degeneration, and reduces acute pain after discectomy in rat and rabbit discectomy models
The present findings indicate the utility of UPAL gel as treatment for IVD herniation that prevents IVD tissue degeneration, and for suppresses inflammation, potentially reduced neoinnervation as suggested by the downregulation of tyrosine kinase A (TrkA) expression, and alleviates pain induced IVD injury after discectomy
Summary
Lumbar intervertebral disc (IVD) herniation causes severe low back pain (LBP), which results in substantial financial and emotional strains. UPAL gel implantation suppressed TNF-α and IL-6 production, downregulated TrkA expression, inhibited IVD degeneration, and reduced nociceptive behaviour. We have previously revealed the reparative effect of the acellular bioresorbable ultra-purified alginate (UPAL) gel, an innovative biomaterial, on damaged tissues in rabbit and sheep discectomy models[22]. In both models, UPAL implantation resulted in reduced IVD degeneration as evidenced by histological and magnetic resonance imaging (MRI) findings, as well as increased Type 2 collagen expression on immunohistochemistry compared to discectomy a lone[22]. To date, its pain-relieving effects, as well as underlying molecular mechanisms, have not been investigated in animal studies
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