胶原酶化学髓核溶解术机制的再研究

目的:研究胶原酶盘内注射对山羊腰椎间盘突出模型的化学髓核溶解作用,重新评估化学髓核溶解术的机制。方法:胶原酶注射前10周,通过手术损伤椎间盘前外侧纤维环诱发椎间盘突出和退变,并经MRI证实。胶原酶注射后1天、1周、2周、4周、12周观察X线片上椎间盘高度指数、椎间盘的组织学等变化。结果:胶原酶对正常和退变椎间盘髓核组织具有类似的溶解作用。胶原酶盘内注射后在突出模型椎间盘中央和髓核突出部位均出现溶解空腔,终板破坏轻;而对正常椎间盘溶解部位在椎间盘髓核和内层纤维环,并严重破坏终板。结论:盘内注射胶原酶能有效溶解山羊突出模型椎间盘的中央和突出部位髓核组织。胶原酶注射后12周,退变间盘基质出现再生能力。     

Low-dose interleukin-1 partially counteracts osteogenic protein-1-induced proteoglycan synthesis by adult bovine intervertebral disk cells

OBJECTIVE: Low back pain associated with degenerative disk disease is a common clinical problem that has enormous socioeconomic impact in today's aging population. As an alternative to the surgical removal of the diseased intervertebral disk, the direct application of a purified growth factor into the intervertebral disk may provide physiatrists a valuable tool to halt or slow down disk degeneration. Our goal here is to determine if low levels of interleukin-1 (IL-1), a proinflammatory cytokine present in the degenerating disk, could interfere with the potentially beneficial effects of growth factors on proteoglycan synthesis. New knowledge gained from this study will prove useful in the development of new treatment modalities that take advantage of the stimulatory effects of growth factors such as osteogenic protein-1 (OP-1). DESIGN: This was an in vitro study of proteoglycan accumulation and synthesis by cells from the nucleus pulposus, inner annulus fibrosus, and outer annulus fibrosus in the bovine intervertebral disk. RESULTS: In cells cultured with serum and no additional exogenous growth factor, treatment with low-dose IL-1 does not result in a significant decrease in proteoglycan synthesis. However, in the case of cells stimulated with OP-1, treatment with IL-1 resulted in a statistically significant decrease in sulfur-35-proteoglycan synthesis by cells derived from all three zones of the bovine intervertebral disk (nucleus pulposus, 60.3% [P < 0.0001]; inner annulus fibrosus, 18.4% [P = 0.0330]; outer annulus fibrosus, 12.3% [P = 0.0255]). Proteoglycan accumulation over the 12-day culture period also decreased significantly (nucleus pulposus, 26.8% [P < 0.0001]; inner annulus fibrosus, 15.8% [P = 0.0276]; outer annulus fibrosus, 16.8% [P = 0.0102]). It is worth noting that cells cultured in the presence of both OP-1 and IL-1 synthesized proteoglycan at a faster rate than cells cultured in the presence of IL-1 alone (nucleus pulposus, 58.5% [P < 0.0001]; inner annulus fibrosus, 39.7% [P = 0.0055]; outer annulus fibrosus, 45.1% [P = 0.0164]). Likewise, cells treated with OP-1 and IL-1 accumulated more proteoglycan in their newly formed matrix than cells cultured in the presence of IL-1 alone (nucleus pulposus, 65.3% [P < 0.0001]; inner annulus fibrosus, 60.5% [P = 0.0034]; outer annulus fibrosus, 19.4% (P = 0.0840]). CONCLUSIONS: Intervertebral disk cells that are stimulated by the growth factor OP-1, to increase the rate at which they produce a proteoglycan-rich matrix become more susceptible to the inhibitory effects of the proinflammatory cytokine IL-1 on the rate of proteoglycan synthesis and accumulation in the matrix over time. This notwithstanding, IL-1 at the low dose used did not totally obliterate the stimulatory effects of OP-1 on matrix formation. Consequently, this growth factor may remain partially effective in stimulating disk repair in vivo even when proinflammatory cytokines such as IL-1 are present.     

神经肽Y/降钙素基因相关肽在腰椎间盘中的分布与共表达

背景：研究发现,神经肽Y与降钙素基因相关肽在交感神经节中有共存现象。目的：观察神经肽Y/降钙素基因相关肽在正常腰椎间盘的共分布及在突出腰椎间盘髓核组织中的共表达。方法：从10例尸体中收集完整的腰椎间盘,在另10例尸体中收集腰椎间盘髓核组织作为对照组。收集30例有症状的腰椎间盘突出症患者,其中L4/5或L5/S1需行腰椎间盘髓核摘除,取出髓核组织作为实验组。结果与结论：①正常椎间盘组织中神经肽Y/降钙素基因相关肽荧光双标染色阳性的神经纤维较多的分布于椎间盘纤维环外1/3,但在椎间盘内2/3及髓核中未见或少量分布。②髓核的共表达,神经肽Y/降钙素基因相关肽荧光双标染色神经纤维的阳性率实验组均高于对照组（P〈0.05）。提示在正常腰椎间盘组织中神经肽Y/降钙素基因相关肽分布于纤维环外1/3部分,在纤维环内2/3部分及髓核组织未分布,但在突出椎间盘髓核组织中有大量的神经肽Y/降钙素基因相关肽共表达。     

针刺损伤免椎间盘退变模型组织病理变化及软骨样细胞的迁移规律

背景：兔椎间盘退变模型间盘退变表现为随时间进展脊索细胞将被软骨样细胞逐渐替代,但兔针刺纤维环间盘退变模型中软骨样细胞的来源和移行规律尚不明确。目的：观察针刺兔纤维环间盘退变模型椎间盘病理变化过程,并初步探讨软骨样细胞来源及移行规律。方法：将24只新西兰大白兔随机分为手术组与假手术组。手术组使用16G穿刺针针刺L2/L3、L3/L4、L4/L5及L5/L6椎间盘纤维环,假手术组暴露至相同椎间盘前方后冲洗闭合伤口。结果与结论：针刺损伤椎间盘退变过程中的软骨样细胞来源于终板。在髓核与上下终板交界处,软骨细胞脱离终板成串向髓核中心迁移;在髓核与内层纤维环交界处,软骨细胞沿纤维走行迁移并随之向皱缩的髓核边缘迁移。椎间盘退变过程中非钙化层逐渐变薄,非钙化层/钙化层比值逐渐降低。     

针刺损伤兔椎间盘退变模型组织病理变化及软骨样细胞的迁移规律

背景:兔椎间盘退变模型间盘退变表现为随时间进展脊索细胞将被软骨样细胞逐渐替代,但兔针刺纤维环间盘退变模型中软骨样细胞的来源和移行规律尚不明确.目的:观察针刺兔纤维环间盘退变模型椎间盘病理变化过程,并初步探讨软骨样细胞来源及移行规律.方法:将24只新西兰大白兔随机分为手术组与假手术组.手术组使用16 G穿刺针针刺L2/L3、L3/L4、L4/L5及L5/L6椎间盘纤维环,假手术组暴露至相同椎间盘前方后冲洗闭合伤口.结果与结论:针刺损伤椎间盘退变过程中的软骨样细胞来源于终板.在髓核与上下终板交界处,软骨细胞脱离终板成串向髓核中心迁移;在髓核与内层纤维环交界处,软骨细胞沿纤维走行迁移并随之向皱缩的髓核边缘迁移.椎间盘退变过程中非钙化层逐渐变薄,非钙化层/钙化层比值逐渐降低.     

颈椎不稳对邻近节段椎间盘蛋白多糖及II型胶原的影响

背景：颈椎行减压融合内固定术后邻近节段椎间盘加速退变,单个节段不稳是否也会加速邻近节段椎间盘退变还不清楚。目的：研究颈椎不稳动物模型邻近节段椎间盘形态学、蛋白多糖及Ⅱ型胶原的变化。方法：16只新西兰大白兔,随机分为实验组及对照组,每组8只。实验组通过颈椎前路穿刺破坏纤维环及抽吸C5/6髓核组织建立兔颈椎不稳动物模型,12周X射线证实退变后处死动物取材,切取C4/5椎间盘组织,从矢状面切开,取其髓核组织10 mg,间苯三酚法测定髓核中蛋白多糖的量,另取椎间盘组织制作石蜡切片后进行苏木精-伊红染色和SABC免疫组化染色观察。结果与结论：实验组 C4/5椎间盘髓核脊索细胞减少,被成纤维细胞样细胞取代,偶见圆形的软骨细胞,且椎间盘纤维环变得粗糙,排列紊乱,玻璃样变性及色素沉着,可见纤维软骨细胞,内外层纤维环之间形成裂隙。髓核中蛋白多糖的含量降低,与对照组相比差异有显著性意义。退变椎间盘髓核及纤维环中Ⅱ型胶原也较对照组明显减少。结果表明颈椎不稳可诱发邻近节段颈椎退变,表现为椎间盘发生形态学变化,蛋白多糖、Ⅱ型胶原含量下降。     

Quality of motion considerations in numerical analysis of motion restoring implants of the spine

BACKGROUND: Motion restoring implants function in a dynamic environment that encompasses the full range of spinal kinematics. Accurate assessment of the in situ performance of these devices using numerical techniques requires model verification and validation against the well-established nonlinear quality of motion of the spine, as opposed to the previous norm of matching kinematic endpoint metrics such as range of motion and intervertebral disc pressure measurements at a single kinematic reference point. METHODS: Experimental data was obtained during cadaveric testing of nine three-functional spinal unit (L3-S1) lumbar spine segments. Each specimen was tested from 8 Nm of applied flexion moment to 6 Nm of applied extension moment with an applied 400 N compressive follower preload. A nonlinear kinematic curve representing the spinal quality of motion (applied moment versus angular rotation) for the index finite element model was constructed and compared to the kinematic responses of the experimental specimens. The effect of spinal soft tissue structure mechanical behaviors on the fidelity of the model's quality of motion to experimental data was assessed by iteratively modifying the material representations of annulus fibrosus, nucleus pulposus, and ligaments. FINDINGS: The present work demonstrated that for this model, the annulus fibrosus played a small role in the nonlinear quality of motion of the model, whereas changes in ligament representations had a large effect, as validated against the full kinematic range of motion. An anisotropic continuum representation of the annulus fibrosus was used, along with nonlinear fabric representations of the ligaments and a hyperelastic representation of the nucleus pulposus. INTERPRETATION: Our results suggest that improvements in current methodologies broadly used in numerical simulations of the lumbar spine are needed to fully describe the highly nonlinear motion of the spine.     

兔腰椎间盘髓核穿刺抽吸后的影像及组织病理学变化

背景：髓核摘除后椎间盘会随时间出现什么样的影像学及组织病理学变化,目前尚不明确。目的：观察兔腰椎间盘髓核穿刺抽吸术后影像学及组织病理学的变化。方法：32只日本大耳白兔,用21号针头行L3“椎间盘后外侧穿刺抽吸出部分髓核组织,L2/3椎间盘作为正常对照椎间盘,于抽吸后2,4,8,12周时按照分组取8只兔子行腰椎侧位X射线检查,测量L3/4、L2／3椎间隙高度并计算椎间盘高度指数,行正中矢状位MRI检查及椎间盘组织病理学检查。结果与结论：髓核抽吸后2,4,8,12周椎间盘高度呈逐渐降低趋势,但8-12周变化减小,与正常对照组椎间盘相比,各时间点椎间盘高度指数显著降低（尸〈0．05）。抽吸后2,4,8,12周的髓核信号强度随时间逐渐降低,8周时已达改良Thompson分级标准的4级。抽吸后凝胶状髓核组织随时间逐渐出现裂隙,形态逐渐紊乱,12周时呈现明显的纤维化表现,髓核4周时出现较多的类软骨细胞,呈现活跃状态,髓核细胞明显减少,抽吸后8．12周髓核内纤维样细胞增多,类软骨细胞数量减少,纤维环随时间逐渐出现扭曲,排列紊乱,突起,出现分层、纤维断裂现象。说明后外侧纤维环穿刺髓核抽吸后,兔腰椎间盘X射线高度、MRIT2加权信号强度随时间逐渐降低、减弱,椎间盘组织逐渐出现退变病理改变,但8—12周其变化趋于缓和。     

经皮纤维环穿刺法建立兔椎间盘退行性变动物模型

背景:合适的椎间盘退变动物模型是椎间盘组织工程研究的必要条件,但目前尚缺乏公认的模型制备方法。目的:采用C形臂辅助下经皮纤维环穿刺法制备兔椎间盘退变动物模型,并评估其可行性。方法:选定新西兰大白兔L2/3和L3/4椎间盘作为穿刺干预椎间盘,L1/2和L5/6椎间盘作为空白对照组,采用C形臂辅助下经皮穿刺法干预椎间盘。于术后2,4,8,12周各选择2只兔麻醉后拍摄兔腰椎核磁共振影像,处死动物采集椎间盘,进行椎间盘髓核蛋白多糖测定。核磁共振检查观察椎间盘退行性改变,二甲基亚甲蓝染色分光光度法测定髓核中蛋白多糖含量变化。结果与结论:术后4周穿刺干预椎间盘髓核区域核磁共振信号强度及髓核内蛋白多糖含量同空白对照组相比均下降(P<0.05),其后两者呈现逐渐下降趋势。结果证实,C形臂X射线机辅助下经皮纤维环穿刺法可用于椎间盘退变动物模型的制备。     

经皮纤维环穿刺法建立兔椎间盘退行性变动物模型

背景：合适的椎间盘退变动物模型是椎间盘组织工程研究的必要条件,但目前尚缺乏公认的模型制备方法。目的：采用C形臂辅助下经皮纤维环穿刺法制备兔椎间盘退变动物模型,并评估其可行性。方法：选定新西兰大白兔L2/3和L3/4椎间盘作为穿刺干预椎间盘,L1/2和L5/6椎间盘作为空白对照组,采用C形臂辅助下经皮穿刺法干预椎间盘。于术后2,4,8,12周各选择2只兔麻醉后拍摄兔腰椎核磁共振影像,处死动物采集椎间盘,进行椎间盘髓核蛋白多糖测定。核磁共振检查观察椎间盘退行性改变,二甲基亚甲蓝染色分光光度法测定髓核中蛋白多糖含量变化。结果与结论：术后4周穿刺干预椎间盘髓核区域核磁共振信号强度及髓核内蛋白多糖含量同空白对照组相比均下降（P〈0.05）,其后两者呈现逐渐下降趋势。结果证实,C形臂X射线机辅助下经皮纤维环穿刺法可用于椎间盘退变动物模型的制备。     

置入棘突间稳定系统Wallis治疗腰椎退变性疾病:与单纯腰椎管减压的比较

背景:在早期,腰椎问盘退变性疾病的治疗临床常用髓核摘除或髓核摘除加刚性内固定融合技术,但是随着非刚性固定技术的发展,棘突间稳定系统固定和全椎间盘置换在脊柱非融合治疗中逐渐受到人们的重视,其优点日益突出.目的:与单纯腰椎管减压相比,评价腰椎管减压并棘突间稳定系统wallis置入固定治疗腰椎退变性疾病的效果.方法:选择2007-12/2008-12华中科技大学附属同济医院骨科收治的腰椎退变性疾病患者40例,随机选取20例行单纯髓核摘除(对照组),20例行突出髓核摘除加棘突间稳定系统wallis固定(实验组).分别于置入后1周,1年对两组患者分别进行JOA评分、目测类比评分.结果与结论:两组患者置入后1周JOA评分及目测类比评分差异均无显著性意义(P>0.05);术后1年JOA评分及目测类比评分差异均有显著性意义(P<0.05).提示两术式即刻效果无差异,均取得良好的效果,此效果主要依赖于手术有效的减压.实验组中期效果明显优于乙组,主要是棘突间稳定系统Wallis发挥良好的生物学作用,有效缓解了患者残余的慢性下腰痛.     

电镜观察胶原酶治疗椎间盘突出症无效原因探讨

目的探讨胶原酶对部分椎间盘突出病人治疗无效的原因.方法采集胶原酶溶解术后无效病人纤维环及髓核,经扫描及透射电镜观察.结果电镜下见胶原酶注入部位纤维呈束索样溶解性断裂,似短毛刷样聚集杂乱,髓核溶解坏死,细胞膜破碎,线粒体溃烂不清.结论部分病人无效的原因为药液未注入纤维环中央区或药量不足.     

组织工程椎间盘纤维环的研究与进展

背景：组织工程是永久性修复退变椎间盘的新策略,然而髓核组织工程方法无法完整重建椎间盘的结构和功能,所以,相应的纤维环组织工程被认为是组织工程椎间盘治疗策略的主要限制因素之一。目的：综述组织工程椎间盘纤维环的研究与进展,为组织工程椎间盘研究提供理论基础。方法：由第一作者用计算机检索Pubmed、CNKI及维普数据库,限定时间为2000/2010,中英文检索词分别为＂组织工程、椎间盘、纤维环、种子细胞、支架材料、生长因子＂和＂tissue engineering,intervertebral disc,annulus fibrosus,seed cell,scaffold,growth factor＂,语言分别设定为中文和英文。从组织工程椎间盘纤维环的种子细胞来源,支架材料选择,生长因子3方面进行归纳介绍。结果与结论：共检索到106篇文章,按纳入和排除标准对文献进行筛选,保留34篇文章进行综述。目前组织工程椎间盘研究重点在构建纤维环组织与髓核组织上。关于功能化纤维环的构建还处于起始阶段,种子细胞、支架材料以及生长因子的选取仍需进一步的实验研究。     

腰椎间盘内破裂模型的建立

目的：建立腰椎间盘内破裂模型并行组织学和椎间盘造影CT观察。方法：15只山羊，手术损伤L5,6前部全层纤维环，L6，7后部纤维环内层，术后3周和3、6个月观察椎间盘造影CT的变化，并进行组织学检查，评定纤维环损伤后的病理改变。结果：组织学和椎间盘造影CT显示L4，5和L5,6在实验期间未发现有后部纤维环内破裂，L6,7后部纤维环内层破裂处未愈合，并在3、6个月时破裂向纤维环外部不断延伸，但均未穿破纤维环外层。结论：经山羊腰椎间盘前方人为损伤后部纤维环内层，可以可靠、一致地制备椎间盘内破裂动物模型。     

经皮纤维环穿刺与经肌间隙纤维环刀刺建立兔椎间盘退变模型

背景：有研究表明椎间盘退变模型的建立可为椎间盘退变治疗提供实验载体,但目前尚缺乏公认的最佳实验动物模型。 目的：比较经皮纤维环穿刺法和经肌间隙纤维环刀刺法建立兔椎间盘退变模型的差异。 方法：将新西兰大白兔分别采用经皮纤维环穿刺法和经肌间隙纤维环刀刺法建立兔椎间盘退变模型,穿刺后4,8,16周通过磁共振和组织病理学检查观察腰椎间盘髓核变性及组织病理情况。 结果与结论：穿刺后4周,两组兔椎间盘髓核内T2加权像信号降低、变暗,椎间隙高度下降,但经皮纤维环穿刺组T2信号强度评分较经肌间隙纤维环刀刺组低（P〈0.05）;穿刺后8周,两组T2信号强度评分均增高,经皮纤维环穿刺组T2信号强度评分较经肌间隙纤维环刀刺组低（P〈0.05）;穿刺后16周,两组兔椎间盘髓核内T2信号强度评分达最高且差异无显著性意义,两组椎间隙均明显变窄,椎间盘均亮度变黑,两组差异不明显;经皮纤维环穿刺组手术时间少于经肌间隙纤维环刀刺组（P〈0.05）,经肌间隙纤维环刀刺组感染率为5.6%,而经皮纤维环穿刺组无感染。结果证实,经皮纤维环穿刺法建立兔椎间盘退变模型建模时间短,感染率低,效果优于经肌间隙纤维环刀刺法造模。     

射频温控热凝术联合臭氧消融术治疗椎间盘源性坐骨神经痛效果观察

目的探讨射频温控热凝术联合臭氧消融术治疗椎间盘源性坐骨神经痛的效果。方法将我院2005~2008年收治的椎间盘源性坐骨神经痛624例随机分为治疗组和对照组,每组各312例。两组均行射频温控热凝术,在CT引导下于病变间盘中心或靠近突出物的纤维环内插入热凝电极,行60 s、96℃剂量射频热凝治疗3次。治疗组随后沿穿刺针注入40μg/ml臭氧10~30 ml行臭氧消融术。结果治疗组显效280例(89.7%),有效21例(6.7%),总有效率96.5%;对照组显效150例(48.1%),有效141例(45.2%),总有效率93.3%。治疗组显效率明显高于对照组(P<0.05)。结论射频温控热凝术联合臭氧消融术治疗椎间盘源性坐骨神经痛效果优于单纯射频温控热凝术。     

Treatment of the degenerated intervertebral disc; closure,repair and regeneration of the annulus fibrosus

Degeneration of the intervertebral disc (IVD) and disc herniation are two causes of low back pain. The aetiology of these disorders is unknown, but tissue weakening, which primarily occurs due to inherited genetic factors, ageing, nutritional compromise and loading history, is the basic factor causing disc degeneration. Symptomatic disc herniation mainly causes radicular pain. Current treatments of intervertebral disc degeneration and low back pain are based on alleviating the symptoms and comprise administration of painkillers or surgical methods such as spinal fusion. None of these methods is completely successful. Current research focuses on regeneration of the IVD and particularly on regeneration of the nucleus pulposus. Less attention has been directed to the repair or regeneration of the annulus fibrosus, although this is the key to successful nucleus pulposus, and therewith IVD, repair. This review focuses on the importance of restoring the function of the annulus fibrosus, as well as on the repair, replacement or regeneration of the annulus fibrosus in combination with restoration of the function of the nucleus pulposus, to treat low back pain. Copyright © 2014 John Wiley & Sons, Ltd.     

髓核细胞移植抑制椎间盘退变

背景：近年来,椎间盘细胞移植和椎间盘移植修复椎间盘退变研究取得较大的进展。目的：探讨髓核细胞的体外培养方法以及髓核细胞移植在抑制椎间盘退变研究中的作用。方法：通过数据库检索的方式探讨髓核细胞移植抑制椎间盘退变的研究。髓核细胞的主要功能是产生胶原和蛋白聚糖,改进髓核细胞的培养方法,使培养后的髓核细胞数量增多,合成和分泌细胞外基质增加,通过髓核细胞移植来修复退变的椎间盘。结果与结论：通过三维小球聚集培养、微载体旋转立体培养等方法可以使髓核细胞数量增多,肝细胞生长因子对髓核细胞增殖产生促进作用。髓核细胞移植可以恢复退变椎间盘高度,促进退变椎间盘内蛋白多糖和Ⅱ型胶原的生物合成和分泌。随着对椎间盘退变研究的不断深入,髓核细胞移植对退变椎间盘可能是一种重要的治疗手段。     

腰椎间盘突出症的CTD影像学表现

目的：探讨腰椎间盘突出症在CTD影像的表现及其临床意义。方法：作椎间盘造影后追加CT扫描，观察椎间盘病变形态、纤维环破裂部位、髓核突出走向并将CTD与临床对比。结果：72例中显像不清3例；椎间盘突出像分3型，退变分4度；纤维环的破裂大多发生在后中央区（73．9％），髓核从后中央途径 出后62％再发生偏移；术中所见髓核突出状况与CTD提示符合率74．2％，CTD1、2型分别相当膨隆型和突出型，3型多为游离型；临床症状与髓核突出后位置有关。结论：CTD能从水平面详细显示椎间盘的局部细微病变，为腰椎间盘突出症的诊断和治疗方法的选择提供确切依据。     

Geometric and morphological changes of the intervertebral disc under fatigue testing

OBJECTIVE: To understand the injury mechanism of the intervertebral disc at different loading rates and to explore the anatomic and histological changes of intervertebral discs. DESIGN: Fresh porcine lumbar spines were used for fatigue testing to study the morphological changes of the intervertebral disc. BACKGROUND: Intervertebral disc problem is one of the most common causes that lead to low back pain. Slow repetitive loading was considered to be the critical factor of spine and disc injuries. METHODS: Twenty-four lumbar functional units were subjected to cyclic loading at three different loading rates. The geometric measurements and magnetic resonance image observations were conducted for the comprehension of morphological changes. The detail observation was taken through a stereomicroscope. RESULTS: There was no significance in geometric changes between different loading rates. For magnetic resonance imagings, morphological changes included the changes of nucleus pulposus shape, bulge of anterior and posterior longitudinal ligaments, and dehydration in annulus fibrosus. CONCLUSION: The morphological changes of intervertebral disc were revealed in certain kinds of lesions. The results imply that fatigue failure and degeneration or instability are strongly linked. The correlation of magnetic resonance imaging and anatomic observation showed a high correspondence in the comparison of shape and position of the nucleus pulpasus. RELEVANCE: The changes of geometric measurements and relationship between anatomic observation and magnetic resonance imaging finding had been analyzed. It could help in understanding the mechanism of triggering cause in the early stage of disc degeneration.