Histological changes in intervertebral discs after smoking and cessation: experimental study using a rat passive smoking model

Background Passive smoking has been reported to induce intervertebral disc degeneration in rats, and the objective of the present study was to histologically investigate changes in smoking-induced intervertebral disc degeneration after cessation of smoking. Methods Four-week-old rats were subjected to passive smoking for 8 weeks in a smoking box [20 cigarettes a day: one cigarette an hour (inhaled over 3 minutes and followed by ventilation with room air for 5 minutes)] to induce intervertebral disc degeneration. Smoke-free periods of different lengths were then established, and intervertebral discs were histologically analyzed. Results Immediately after 8 weeks of passive smoking, intervertebral discs exhibited cracks, tears, and misalignment of the annulus fibrosus, and increased fibrous tissue was seen in the nucleus pulposus. In addition, the level of interleukin-1β in intervertebral discs was higher in the smoking group than in the non-smoking group. After cessation, progression of degeneration ceased, and the matrix of the nucleus pulposus and annulus fibrosus exhibited increased fibrous connective tissue and proteoglycan. However, there were no changes in annulus fibrosus misalignment. Interleukin-1β levels also remained significantly elevated after 8 weeks of cessation. Conclusions While the annulus fibrosus degeneration caused by smoking was partially irreversible after cessation of smoking, the amount of mucin (proteoglycan) in the nucleus pulposus and annulus fibrosus tended to increase after cessation, thus suggesting the possibility that smoking-induced intervertebral disc degeneration can be repaired to some degree by cessation of smoking.     

Changes with age in proteoglycan synthesis in cells cultured in vitro from the inner and outer rabbit annulus fibrosus. Responses to interleukin-1 and interleukin-1 receptor antagonist protein

STUDY DESIGN: Proteoglycan synthesis was examined in cells isolated from the inner and outer annulus fibrosus of young and old rabbits. Their responses to interleukin-1 alpha and interleukin-1 receptor antagonist protein were investigated. OBJECTIVES: To evaluate the age-related changes and the anatomically related differences in the function of intervertebral disc cells. SUMMARY OF BACKGROUND DATA: Proteoglycan content in the human intervertebral disc decreases with age. Age-related changes in intervertebral disc cell function, however, have not been fully investigated. METHODS: Japanese white rabbits aged 2 months (young group) and 3 years (old group) were used. The inner and outer layer of the annulus fibrosus were separated. The proteoglycan synthesis and release were measured in cells cultured with or without human recombinant interleukin-1 alpha and interleukin-1 receptor antagonist protein. RESULTS: The proteoglycan synthesis significantly decreased and the release rate significantly increased in the old rabbits, compared with the young ones. In the inner annulus, the inhibition of proteoglycan synthesis due to interleukin-1 alpha was greater in the old rabbits than in the young ones. In the old rabbits, interleukin-1-induced inhibition was more pronounced in the inner annulus than in the outer annulus. Interleukin-1 receptor antagonist protein suppressed inhibition of proteoglycan synthesis by interleukin-1 alpha in the two layers in both age groups. CONCLUSIONS: Both the decline in proteoglycan synthesis and the increased cell sensitivity to interleukin-1 alpha with age may contribute to the degradation of discs. The increase in cell response to interleukin-1 alpha in the inner annulus of rabbits may explain why the inner annulus and nucleus pulposus degrade earlier than the outer annulus in human discs. Interleukin-1 receptor antagonist protein could be useful in inhibiting the degradation of the disc.     

实验性脊柱内固定后相应区域椎间盘超微结构观察

目的　观察脊柱内固定后相应区域椎间盘的超微结构变化。　方法　日本大耳白兔2 4只,随机分成实验组和对照组,每组12只。实验组骨膜下游离T1 0 ～L3棘突和关节突,克氏针制成“L”形,将钢丝横行穿过T1 1、1 2 ,L1、2 的关节突关节,并与置于T1 1 ～L3棘突两旁的克氏针系紧,对相应区域的脊柱行内固定术。对照组未行手术,仅喂养至实验完成。术后6个月,对两组动物摄X线片观察1次,随后处死动物。取两组动物的L1 椎间盘组织(髓核、纤维环内侧及纤维环外侧)行透射电镜观察,对两组T1 2 、L2 椎间盘组织分别行水平面和矢状面透射电镜及扫描电镜观察。　结果　X线片显示,实验组与对照组椎体及椎间隙差别不明显;透射电镜与扫描电镜观察,实验组椎间盘的髓核、纤维环内层细胞的结构改变较纤维环外层早;对照组的髓核、纤维环内层细胞的结构改变与纤维环外层差别不明显。在退变的椎间盘基质中,蛋白多糖颗粒和特殊结构明显减少。髓核与纤维环基质内有蛋白多糖颗粒和一种特殊结构,而特殊结构在髓核与纤维环内层的形态不一致。　结论　脊柱内固定术后6个月,实验组在异常应力环境下发生椎间盘退变。髓核、纤维环内层基质内的特殊结构分布有特殊规律,与蛋白多糖颗粒在椎间盘退变中的生物学行为密切相关。     

微载体立体培养腰椎间盘细胞蛋白多糖表达的研究

目的研究腰椎间盘细胞在微载体培养与单层培养中细胞表达蛋白多糖含量的差别。方法椎间盘疾病手术病例的术中切除组织采用酶消化法分别进行微载体三维细胞培养和单层细胞培养；取胎儿椎间盘组织，显微镜下区分髓核细胞和纤维环细胞，分别进行培养，同成入组对照。利用^35S放射标记渗入放免定量测定的方法进行蛋白多糖含量的检测。结果①椎间盘细胞胞内的蛋白多糖含量（cpm），细胞单层培养组为101．909±11．439，微载体立体培养组为136．607±10．792，P〈0．05；②椎间盘细胞表达的蛋白多糖含量（cpm），细胞单层培养组为105．119±13．040，微载体立体培养组为174．231±17．676，P〈0．05；③各组椎间盘细胞表达的蛋白多糖含量均高于细胞内的含量；④胎儿腰椎间盘细胞蛋白多糖的含量及表达量均高于成人退变椎间盘细胞，胎儿髓核细胞蛋白多糖的表达量高于纤维环细胞的表达量。结论椎间盘细胞的微载体三维立体培养相对单层培养具有较高细胞蛋白多糖的表达量，是一种较好的细胞培养方式。     

Articular cartilage and intervertebral disc proteoglycans differ in structure: an electron microscopic study

Articular cartilage and the intervertebral disc tissues have different material and biological properties and different patterns of aging and degeneration. To determine if the proteoglycans of these tissues differ in structure, we used the electron microscopic monolayer technique to compare baboon articular cartilage proteoglycans with baboon annulus fibrosus, transition zone, and nucleus pulposus proteoglycans. Intervertebral disc and articular cartilage proteoglycans differed significantly. Articular cartilage contained large proteoglycan aggregates formed from hyaluronic acid central filaments, multiple monomers, and large nonaggregated monomers. These molecules were identical to those of nasal cartilage, growth plate cartilage, chondrosarcomas, or menisci. In contrast, the intervertebral disc tissues contained only nonaggregated proteoglycan monomers and clusters of monomers without apparent central filaments. Intervertebral disc nonaggregated monomers were shorter and more variable in length than those from articular cartilage, and nucleus pulposus nonaggregated monomers were even shorter and more variable in length than transition zone and annulus fibrosus monomers. These observations suggest that significant differences in proteoglycan metabolism exist between articular cartilage and intervertebral disc.     

Effects of aging and degeneration on the human intervertebral disc during the diurnal cycle: A finite element study

A significant biochemical change that takes place in intervertebral disc degeneration is the loss of proteoglycans in the nucleus pulposus. Proteoglycans attract fluid, which works to reduce mechanical stresses in the solid matrix of the nucleus and provide a hydrostatic pressure to the annulus fibrosus, whose fibrous nature accommodates this stress. Our goals are to develop an osmo‐poroelastic finite element model to study the relationship between proteoglycan content and the stress distribution within the disc and to analyze the effects of degeneration on the disc's diurnal mechanical response. Stress in the annulus increased with degeneration from ～0.2 to 0.4 MPa, and an increase occurred in the center of the nucleus from 1.2 to 1.6 MPa. The osmotic pressure in the central nucleus region decreased the most with degeneration, from ～0.42 to ～0.1 MPa in a severely dehydrated disc. A 3% decrease in diurnal fluid lost with degeneration equated to ～21% decrease in fluid exchange, and hence a decrease in nutrients that require convection to enter the disc. We quantified the increases in internal stresses in the nucleus and annulus throughout the various stages of degeneration, suggesting that these changes lead to further remodeling of the tissue. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:122–128, 2012     

Advances in Magnetic Resonance Imaging for the assessment of degenerative disc disease of the lumbar spine

The intervertebral disc is characterized by a tension-resisting annulus fibrosus, and a compression-resisting nucleus pulposus composed largely of proteoglycan. Both the annulus and the nucleus function in concert to provide the disc with mechanical stability. Early disc degeneration begins in the nucleus with proteoglycan depletion. Quantitative MRI techniques have been developed to non-invasively quantify the earliest degenerative changes that occur within the disc. Our ability to identify and quantify these early biochemical changes will provide a better understanding of the pathophysiology of disc degeneration and facilitate the study of interventions that aim to halt or reverse the degenerative process.     

Chemonucleolysis--an experimental histopathological study

To investigate the histopathological changes of the intervertebral disc after chemonucleolysis, experiments were performed on 21 monkeys. After the injection of chymopapain, animals were sacrificed at definite intervals up to 1 year. Histopathological studies on these specimens revealed disappearance of proteoglycan from the nucleus pulposus, inner annulus fibrosus and cartilaginous endplates as early as 1 day after injection. At 4 weeks, regeneration of proteoglycan was indicated by the recovery of positive Safranin-O (S-O) staining in the area of the nucleus pulposus. After 24 weeks, the entire intervertebral disc showed uniform S-O staining indicating further regeneration of proteoglycan. The matrix of the reformed nucleus pulposus contained increased amount of fibrous elements compared to the controls. These results indicate proteoglycan regeneration by chondrocytes after chemonucleolysis. The reformed nucleus was histopathologically different from the control.     

Proteoglycans of human infant intervertebral disc. Electron microscopic and biochemical studies

The ground substance of the intervertebral disc consists primarily of proteoglycans, which give the tissue its stiffness to compression and its resiliency. To investigate the structure and composition of these molecules, we extracted them from human infant nucleus pulposus under associative conditions and from human infant annulus fibrosus and cartilage end-plate under dissociative conditions. We examined the degree of aggregation, the composition, the electron microscopic appearance, and the dimensions of the proteoglycans of the intervertebral disc and compared their structure and dimensions with those of the proteoglycans from bovine hyaline cartilage. Aggregates represented 52 per cent of the proteoglycans of the nucleus pulposus between the ages of one and ten days but only 28 per cent between the ages of six and eight months. Preparations from the corresponding annuli contained 59 per cent aggregates at one to ten days and 47 per cent at six months. The corresponding cartilage end-plate preparations contained 45 and 40 per cent aggregates. The proteoglycans of the annulus fibrosus and cartilage end-plate contained more protein and less hexosamine than did those of the nucleus pulposus. Electron microscopy showed that approximately two-thirds of the aggregates from nucleus pulposus consisted of very short hyaluronate filaments with closely packed monomers. The other third had longer hyaluronate filaments and wider distances between monomers, and closely resembled the aggregates from the annulus fibrosus and cartilage end-plate. Aggregated monomers consisted of two segments: a thin segment connecting directly to the hyaluronic acid filament and a thick segment extending peripherally from the thin segment. The thin segment formed about 12 per cent of the total monomer length in the samples from all three disc tissues. The lower proportion of aggregated monomers, the lower protein content, and the smaller aggregates with closely packed monomers suggest that the nucleus pulposus may contain less link protein than do the annulus fibrosus and cartilage end-plate. Compared with proteoglycan aggregates from bovine hyaline cartilage, proteoglycan aggregates from human intervertebral disc were shorter and had fewer monomers and wider spacing between monomers. The aggregated monomers from the three components of the intervertebral disc had an average length of 209 +/- 90 nanometers, compared with 210 +/- 114 nanometers for monomers from hyaline cartilage of skeletally mature cows, 250 +/- 116 nanometers for monomers from hyaline cartilage of skeletally immature calves, and 288 +/- 108 nanometers for monomers from fetal animals.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chymopapain, chemonucleolysis, and nucleus pulposus regeneration

In the adult mongrel dog, in vivo injection of chymopapain into the intervertebral disc resulted in disc-space narrowing at two weeks, with a complete loss of proteoglycan (as indicated by safranin-O staining) from the nucleus pulposus, the cartilaginous end-plates, and the annulus fibrosus. As demonstrated by [35S]sulphate-labeling and proteoglycan isolation, the nucleus pulposus retained the ability to synthesize proteoglycans, but these were degraded by endogenous proteolytic activity. Three months after chymopapain treatment the intervertebral disc showed an increase in height. There was a return of intense safranin-O staining in the annulus and the cartilaginous end-plates, and very prominently in the nucleus. The proteoglycans that were present were recovered as aggregates, with the proteoglycan monomer being slightly larger than in the controls. Six months after chymopapain treatment the intervertebral disc had increased further in height, and normal histology had been restored. The chemical composition and physical properties of the proteoglycans that were isolated from the nucleus pulposus were essentially the same as those from the controls. These observations suggest that the nucleus can regenerate following the injection of chymopapain. Clinical Relevance: Our observations demonstrate that chymopapain has a profound but reversible effect on the intervertebral disc. The radiographic narrowing of the intervertebral disc following chymopapain injection correlates with the loss of proteoglycan content and structure. The restoration of normal disc height following chymopapain injection is explained by reconstitution of the intervertebral disc with normal proteoglycans. In experimental animals, chemonucleolysis with chymopapain appears to be less likely than surgical excision to permanently alter the biochemistry of the nucleus pulposus.     

A study on topographical change of proteoglycans in human lumbar disc

Proteoglycan aggregates, the binding of disc proteoglycan to hyaluronate, chondroitin sulfate chain length, hexosamine and amino acid compositions were measured in different regions of the L1/L2 and L4/L5 intervertebral discs from 3 spines aged 35, 49, and 60 years. The results were as follows: proteoglycan aggregates and the binding of disc proteoglycan to hyaluronate were shown to increase from the nucleus pulposus to the outer annulus, while only small differences were observed among the anterior, posterior and lateral regions in either the inner or the outer annulus within a given disc. Changes in chondroitin sulfate chain length were observed with aging. However, within a given disc, and furthermore, within a given spine, chondroitin sulfate chains were similar in length. Glucosamine/galactosamine molar ratios of disc proteoglycan were higher in the L1/L2 disc than the L4/L5 disc. Changes with age were also observed. Nevertheless, only minor differences among the anterior, posterior and lateral regions of the annulus fibrosus were found within a given disc. The amino acid compositions showed small differences when proteoglycans from various regions of a disc were compared. All of them had a high content of aspartic acid, threonine, serine, glutamic acid, proline and glycine. The results indicate that it seems there are only minor differences among the anterior, posterior and lateral regions of the annulus fibrosus in a number of the experimented parameters.     

In vivo macrophage recruitment by murine intervertebral disc cells

SUMMARY: An in vivo murine experiment was conducted to measure the capacities of viable intervertebral disc cells to recruit inflammatory cells. The objective was to determine whether compounds secreted from viable cells induce inflammation or whether inflammation in disc herniation simply requires exposure to structural cell or matrix components. Three tissue preparations were inserted into the right lower peritoneal cavity of male mice: tissue with viable annulus fibrosus and nucleus pulposus cells, tissue with viable annulus fibrosus cells, or devitalized annulus fibrosus and nucleus pulposus tissue. Controls included sham-operated and nonoperated groups. Mice were killed 1, 2, or 7 days after surgery. Macrophage recruitment occurred after exposure to viable disc tissue but not after exposure to devitalized disc components; recruitment increased over time. Viable disc cells play a role in the etiology of inflammation in disc herniation.     

Postmortem changes in ultrastructures of the mouse intervertebral disc

To elucidate the effects of nutrition and oxygen deficiencies on the intervertebral disc, cell components of mouse intervertebral discs and their postmortem changes were observed by electron microscopy. The annulus fibrosus could be divided into an inner and outer region. The main cell components of the annulus fibrosus were fibroblast-like cells in the outer region and chondrocytes in the inner region. The nucleus pulposus consisted of massively packed notochordal cells. The cartilage plates could also be divided into two zones: articular cartilage and growth cartilage containing chondrocytes. Postmortem degenerative changes proceeded from the peripheral to the central parts of the intervertebral disc, ie, showing degeneration of first the fibroblast-like cells, next the chondrocytes, and finally, the notochordal cells. The findings suggest that cells situated at the periphery predominantly depend on aerobic metabolism, whereas the cells situated more centrally depend on anaerobic metabolism. Furthermore, postmortem changes of the nucleus pulposus were similar to age-related changes. The age-related changes or degeneration in the intervertebral disc appear to be related to deficiencies of nutrition or oxygen caused by changes in structures of the disc and the surrounding tissues.     

Analysis of rabbit intervertebral disc physiology based on water metabolism. I. Factors influencing metabolism of the normal intervertebral discs

Basic factors influencing the metabolism of intervertebral discs of rabbits were quantitatively analyzed based on the water metabolism. The blood flow surrounding the intervertebral disc was calculated using pharmacokinetic concepts from the data obtained by time-related tritiated water distribution analyses. The blood flow was estimated as 0.056 (mg/min/mg tissue) in the anterior annulus, 0.106 in the posterior annulus, 0.120 in the lateral annulus, and 0.084 in the nucleus pulposus, respectively (Experiment 1). Water content and fixed charge density in the intervertebral disc fractions also were measured (Experiment 2). The cations and uncharged small solutes transported into the disc tissue ranged in descending order from nucleus pulposus, lateral annulus, posterior annulus, to anterior annulus. The authors also calculated theoretically the swelling pressure of the proteoglycan in the intervertebral disc fractions from the results of Experiment 2. It was concluded that swelling pressure was highest in the nucleus pulposus, and lowest in the anterior annulus. The water in the posterior annulus is less exchangeable than in the other disc tissue fractions.     

腰椎间盘MRI高信号区的组织病理学特点和临床意义

目的研究椎间盘源性下腰痛患者腰椎间盘纤维环后方MRI高信号区的组织病理学特征及其临床意义。方法对52例经保守治疗无效、CT片显示无腰椎间盘突出的下腰痛患者行腰椎MR检查及腰椎间盘造影术。男39例,女13例;平均年龄38.8岁。选择纤维环后方出现高信号区的部分病例行腰椎后路椎间盘切除、椎体间融合、椎弓根螺钉内固定术,术中收集包括高信号区部位的椎间盘。对标本行矢状面连续组织学切片,光镜下观察高信号区椎间盘组织的组织病理学结构,并分析其临床意义。结果在行腰椎间盘造影的52例142个椎间盘中,17例17个椎间盘显示高信号区,且在椎间盘造影过程中全部呈现2或3级的纤维环破裂和疼痛复制反应。敏感性和特异性均为100%。高信号区与纤维环破裂程度分级呈正相关,说明纤维环破裂程度分级越高,越易出现高信号区(R=0.462,P<0.01)。共收集11例患者11个椎间盘,组织学研究发现对应高信号区的椎间盘组织表现为沿纤维环裂隙形成的不同程度的血管化肉芽组织,有成熟的瘢痕化胶原组织。结论症状性下腰痛患者的腰椎MRI上有椎间盘高信号区,可以作为椎间盘源性下腰痛诊断的重要征象。     

Histological study on chemonucleolysis with special reference to the relationship between the dose of chymopapain and disc regeneration

The present study on chemonucleolysis was conducted to determine the influence of chymopapain dose level and patient age on the degree and mode of the response and regeneration of the intervertebral disc. Chymopapain at various doses was injected into the intervertebral discs of young (8-week-old) and mature (20-week-old) rabbits respectively for a histological study. In rabbits undergoing high dose injection, not only the nucleus pulposus but also the inner layer of the annulus fibrosus was digested. Regeneration hardly occurred, and only a slight amount of scar tissue appeared in many animals. At lower dose, the annulus fibrosus remained intact and the posterior inner layer of the annulus fibrosus mainly proliferated toward the anterior portion of the disc, filled the space of digested nucleus pulposus, and restored disc height. This regeneration process was not thought to be specific to the damages caused by chymopapain but rather a common response of injured intervertebral discs.     

Reinsertion of stimulated nucleus pulposus cells retards intervertebral disc degeneration: an in vitro and in vivo experimental study.

Reinsertion of autogenous nucleus pulposus, an innovative method to delay further disc degeneration, has been proved with an experimental animal model. This study examined whether coculture of nucleus pulposus cells with annulus fibrosus cells (a) activates annulus fibrosus cells and (b) retards disc degeneration when reinserted into the disc in a rabbit model of disc degeneration. Coculture of the two cell types stimulated proliferation of each, as indicated by increased DNA synthesis measured by increases in DNA polymerase alpha expression and uptake of 5-bromo-2'deoxy-uridine assessed by an enzyme-linked immunosorbent assay. In a model of disc degeneration in rabbits, reinsertion of activated nucleus pulposus cells delayed the formation of clusters of chondrocyte-like cells, the destruction of disc architecture, and the elaboration of type-II collagen as measured immunohistochemically compared with no treatment. The direct reinsertion of activated nucleus pulposus cells into the disc offers a promising line of investigation for delaying intervertebral disc degeneration, although these results obtained with notochordal cells may not necessarily apply when mature central nucleus pulposus cells are used.     

三种纤维环处理方式对腰椎生物力学影响的三维有限元分析

目的:通过建立"一"字型切口、环形切口、纤维环缝合的有限元分析模型,利用有限元分析方法,评估三种纤维环处理方式对于腰椎生物力学的影响。方法:选取健康成人L4/5腰椎节段的CT的DICOM结果,通过逆向建模方式建立人体正常腰椎模型、环形切口模型、"一"字型切口模型及缝合模型,测量腰椎在正常轴向压力的情况下,前屈、后伸、侧弯、旋转四种工况下的生物力学数据。结果:通过有限元分析方法计算正常椎体及三种不同纤维环处理方式的模型的应力数据,结果显示纤维环切开后,各种工况下纤维环、髓核的最大应力值均较正常模型增加;纤维环缝合后,在前屈后伸旋转工况下的最大应力,均低于"一"字型切口和环形切口;与未缝合模型相比,纤维环缝合模型的各部分在各种工况下的应力分布都更加均匀。结论:纤维环缝合后椎间盘、髓核和纤维环应力分布较未缝合模型均匀,缓解纤维环切开后造成的纤维环应力集中问题,对维持椎间盘的稳定性及防止术后再突出能起到积极作用。     

Cell culture of the intervertebral disc of rats: factors influencing culture, proteoglycan, collagen, and deoxyribonucleic acid synthesis.

To establish cell culture of the nucleus pulposus and anulus fibrosus of rat intervertebral disc, the effects of culture conditions on the growth of cells and the synthesis of DNA, proteoglycan, and collagen were studied. For cell culture of the nucleus pulposus, the use of 3-week-old rats and a medium adjusted to pH 7.0 was optimal. There was almost no difference in growth between cells in Ham's F12 medium and those in Dulbecco's Modified Eagle Medium. In cells isolated from the anulus fibrosus, a medium adjusted to pH 7.0-7.6 was preferable, but irrespective of rat age. Culture cells of the nucleus pulposus were composed of large cells with vacuoles and small polygonal cells. These cells had a slight growth activity and a fair capability of proteoglycan and collagen synthesis. Culture cells of the anulus fibrosus were composed of polygonal and spindle-shape cells, and the growth was more vigorous with the potentials for proteoglycan and collagen synthesis than the nucleus cells.     

椎间盘源性下腰痛的发病机制

目的探讨椎间盘源性下腰痛的发病机制。方法收集腰椎后路切除的17例椎间盘源性下腰痛患者的19个经腰椎间盘造影术证实的疼痛腰椎间盘;同时收集12个在MRI T2加权像上信号强度明显减弱、无腰痛症状的生理老化椎间盘和10个正常对照椎间盘,行组织学检查和P物质、神经丝蛋白和血管活性肠肽的免疫组织化学染色检查。结果椎间盘源性下腰痛患者的疼痛椎间盘在组织学上的显著特征表现为,一条从髓核至纤维环外层的血管化肉芽组织条带区,其间伴有1个或多个裂隙;肉芽组织条带区与椎间盘造影术后CT上显示的纤维环裂隙一致,肉芽组织之外的纤维环结构基本正常。生理老化椎间盘和正常对照椎间盘表现为与年龄相关的改变。免疫组织化学染色显示,疼痛椎间盘中P物质、神经丝蛋白和血管活性肠肽3种神经肽阳性神经纤维分布数量和比例,较正常对照椎间盘和生理老化椎间盘明显增多;神经纤维主要沿伴有裂隙的肉芽组织条带区分布;疼痛椎间盘髓核中可见P物质和神经丝蛋白的阳性神经纤维分布。结论椎间盘后方神经分布广泛的肉芽组织条带区是椎间盘造影术疼痛和椎间盘源性下腰痛的起源部位。肉芽组织条带可能起源于椎间盘的创伤修复过程。生理老化椎间盘和疼痛椎间盘的差异是后者形成组织学上的肉芽组织条带区。