Department of Orthopedic Surgery, Faculty of Medicine and Graduate of Medicine, Hokkaido University, N15W7, Sapporo, Hokkaido, 060-8638, Japan.
Department of Advanced Medicine for Spine and Spinal Cord Disorders, Faculty of Medicine and Graduate of Medicine, Hokkaido University, N15W7, Sapporo, Hokkaido, 060-8638, Japan.
Sci Rep. 2021 Jan 12;11(1):638. doi: 10.1038/s41598-020-79958-9.
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. 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. UPAL gel implantation suppressed TNF-α and IL-6 production, downregulated TrkA expression, inhibited IVD degeneration, and reduced nociceptive behaviour. 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.
腰椎间盘(IVD)突出可导致严重的腰痛(LBP),这会造成巨大的经济和情感压力。尽管椎间盘切除术有效,但对于 IVD 进行性退变引起的术后 LBP 尚无现有治疗方法。LBP 的两个关键因素是椎间盘内炎症,由肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)表示,以及感觉神经向内层纤维环生长,由神经生长因子/高亲和力酪氨酸激酶 A(TrkA)信号触发。在椎间盘切除术的动物模型中,具有极低毒性的可生物吸收的超纯藻酸盐(UPAL)凝胶在去细胞组织修复中非常有效。我们旨在研究 UPAL 凝胶是否可以通过大鼠髓核(NP)穿孔模型和兔 NP 抽吸模型来减轻 LBP。在这两种模型中,我们通过免疫组织化学评估了 IVD 内 TNF-α和 IL-6的产生和 TrkA 表达。此外,在大鼠模型中进行了组织学分析和行为性疼痛检测。UPAL 凝胶植入物可抑制 TNF-α和 IL-6的产生,下调 TrkA 的表达,抑制 IVD 退变,并减轻疼痛行为。我们的研究结果表明,UPAL 凝胶植入物具有通过减轻 LBP和防止椎间盘切除术后 IVD 退变来治疗 IVD 突出症的潜力。