Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus-induced thrombus formation, intraneural edema, and reduction of nerve conduction velocity: possible implications for future pharmacologic treatment strategies of sciatica

STUDY DESIGN: The possibility to prevent nucleus pulposus-induced functional and structural nerve root injury by selective tumor necrosis factor-alpha inhibition was assessed in an experimental model in the pig spine. OBJECTIVE: The objective of the study was to evaluate the role of tumor necrosis factor-alpha in the mediation of nucleus pulposus-induced nerve injury by using selective inhibition. SUMMARY OF BACKGROUND DATA: The cytokine tumor necrosis factor-alpha has been suggested to play a key role in the nerve root injury induced by local application of nucleus pulposus. However, previous studies have not been able to distinguish the effects between tumor necrosis factor-alpha and other disc-related cytokines because of the use of nonspecific cytokine inhibition. METHODS: Autologous nucleus pulposus was harvested from a lumbar disc and applied to the porcine sacrococcygeal cauda equina. The pigs were simultaneously treated with two selective tumor necrosis factor-alpha inhibitors (etanercept n = 8 and infliximab n = 5), a heparin analogue (enoxaparin n = 5) or saline for control (n = 5). After 7 days the nerve conduction velocity over the application zone was determined and samples of the exposed nerve roots were collected for light microscopic evaluation. RESULTS: The two tumor necrosis factor-alpha inhibitors prevented the reduction of nerve conduction velocity and also seemed to limit the nerve fiber injury, the intracapillary thrombus formation, and the intraneural edema formation. However, treatment with enoxaparin did not seem to be different from control regarding reduction of nerve conduction velocity or histologic changes. CONCLUSIONS: The data clearly indicate that tumor necrosis factor-alpha is involved in the basic pathophysiologic events leading to nerve root structural and functional changes after local application of nucleus pulposus. The study therefore provides a basic scientific platform with potential clinical implications regarding the use of anti-tumor necrosis factor-alpha medication as treatment in patients with disc herniation and sciatica.     

Cyclic mechanical stretch stress increases the growth rate and collagen synthesis of nucleus pulposus cells in vitro

STUDY DESIGN: A rabbit model designed to investigate the effects of applied cyclic tensile stress on the cell division rate and the collagen synthesis in the rabbit nucleus pulposus cells in vitro. OBJECTIVE: To evaluate the effects of mechanical stress on nucleus pulposus cells, thus adding to the understanding of the adaptation of the intervertebral disc to mechanical stress. SUMMARY OF BACKGROUND DATA: Intervertebral disc cells in vivo are exposed to a multitude of physical forces during physical motion. Although it is known that in intervertebral disc disease, a common pathway of disc degeneration is mechanical stress on the nucleus pulposus or the anulus fibrosus or both, the underlying mechanism has been less well defined. METHODS: Nucleus pulposus cells were isolated from 4-week-old Japanese white rabbits. These cells were subjected to the mechanical cyclic stretch stress using a computerized, pressure-operated instrument that physically deformed the cells. The DNA synthesis rate, collagen synthesis rate, and cell cycle progression were measured. RESULTS: Cyclic tensile stretch increased the DNA synthesis rate in nucleus pulposus cells and in the population of cells in the S phase of the cell cycle during 1 to 2 days of subjugation to stress. Cyclic tensile stretch also increased collagenous protein synthesis in nucleus pulposus cells during 1 to 4 days of stress. CONCLUSIONS: Mechanical stress on nucleus pulposus cells promotes the proliferation of cells and alters the properties of intervertebral disc cells. This study may reflect the adaptation of the intervertebral disc to increased motion and stress.     

Indomethacin blocks the nucleus pulposus-induced effects on nerve root function

Inflammatory mechanisms have been suggested to be involved in the basic pathophysiologic events leading to nerve root injury after local application of nucleus pulposus. To assess if these nucleus pulposus-induced effects could be blocked by anti-inflammatory treatment, 41 dogs were exposed to either incision of the L6-7 disc to induce experimental disc herniation with (n=12) or without (n=14) indomethacin treatment per os (5 mg/kg per day), and no incision with (n=5) or without (n=10) indomethacin. Intraneural blood flow and nerve conduction velocity were assessed after 7 days to evaluate the degree of nerve injury. Disc incision induced a reduction in nerve root and dorsal ganglion blood flow as well as nerve function, similarly to previous studies. However, simultaneous treatment with indomethacin efficiently blocked the negative effects on both blood flow and nerve conduction but had no effects per se. The present study thus indicates that inflammatory mechanisms may be of relevance in the pathophysiology of nucleus pulposus-induced nerve root injury and thereby also for sciatica.This study was supported by grants from the Fukushima Medical Research Promotion Foundation and the Swedish Medical Research Council (9758)     

Mechanical and biochemical injury of spinal nerve roots: a morphological and neurophysiological study

Compression may induce morphological and neurophysiological changes in nerve roots. However, it has also been demonstrated experimentally that nucleus pulposus, without any compression, may induce similar changes when applied epidurally. The present study was undertaken to examine the morphological and functional effects of autologous nucleus pulposus and the combination of nucleus pulposus and compression in a pig model. Nucleus pulposus from a lumbar disc in the same animal was applied epidurally around the first sacral nerve root in the pig, with or without a specially designed constrictor. After 1 week, nerve root conduction velocity was determined in the exposed and in the contralateral control nerve root by local electrical stimulation and EMG recordings in the back muscles. Nerve root specimens were processed for blinded light-microscopic evaluation. There was a significant reduction in nerve conduction velocity for all exposed nerve roots as well as contralateral control nerve roots when nucleus pulposus had been applied. There were no statistically significant differences between the nerve conduction velocities recorded following the combined application of nucleus pulposus and compression and those recorded after application of nucleus pulposus alone. The reductions were similar to the reduction induced by the constrictor per se, as seen in a previous study. In all series there was also a decrease in conduction velocity in the control nerve roots, in contrast to previous studies. Light microscopy demonstrated axonal changes only in nerve roots exposed to the constrictor. In conclusion, both epidural nucleus pulposus and compression may induce a significant reduction in nerve conduction velocity. The combination, however, of these two agents does not increase the magnitude of such dysfunction. The potency of nucleus pulposus to induce changes in nerve roots after epidural application was further indicated by the fact that reduction in nerve conduction velocity also occurred in the contralateral control nerve roots in this series. The histological data suggest that axonal injury can not alone explain the reduction in nerve conduction velocity, and that the morphological basis for the functional changes must be sought at the subcellular level.     

Age-related changes in fibromodulin and lumican in human intervertebral discs.

STUDY DESIGN: An analysis of proteoglycans of the intervertebral disc using immunoblotting of tissue extracts. OBJECTIVES: To investigate the changes in structure and abundance of fibromodulin and lumican in human intervertebral discs during aging and degeneration. SUMMARY OF BACKGROUND DATA: Fibromodulin and lumican are keratan sulfate proteoglycan constituents of the disc's extracellular matrix, whose interaction with collagen fibrils may contribute to the mechanical properties of the tissue. Changes in their abundance and/or structure that occur with aging and degeneration therefore may have an impact on disc function. METHODS: Lumbar intervertebral discs were obtained from individuals of different ages, and extracts of anulus fibrosus and nucleus pulposus were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using antibodies specific for fibromodulin and lumican. RESULTS: The major changes in abundance observed with age were a decrease in fibromodulin in the adult nucleus pulposus and an increase in lumican in anulus fibrosus during early juvenile development. In addition, fibromodulin in the anulus fibrosus exhibited a structural change with increasing age, characterized by a shift toward the predominance of its glycoprotein form lacking keratan sulfate. Fibromodulin was more abundant in the anulus fibrosus than in nucleus pulposus at all ages, whereas lumican was much more abundant in nucleus pulposus than in anulus fibrosus in the young juvenile; in the adult, however, lumican was present in comparable levels in both tissues. With increasing degrees of degeneration, fibromodulin exhibited an increase in abundance. CONCLUSIONS: Growth, aging, and degeneration of the intervertebral disc are associated with changes in the abundance and structure of fibromodulin and lumican, which presumably influence the functional properties of the tissue.     

Nitric oxide as a mediator of nucleus pulposus-induced effects on spinal nerve roots.

Nerve root dysfunction and sciatic pain in disc herniation are considered to be caused by mechanical compression and related to the presence of nucleus pulposus in the epidural space. Autologous nucleus pulposus has been shown to induce endoneural edema and to decrease nerve-conduction velocity in spinal nerve roots in experimental disc herniation models, and inflammatory mediators have been suggested to be involved in these mechanisms. Nitric oxide, a potent inflammatory mediator, is implicated in vasoregulation, neurotransmission, and neuropathic pain. Nitric oxide synthesis can be induced by different cytokines, e.g., tumor necrosis factor-alpha, which recently was shown to be of pathophysiological importance in experimental disc herniation. The enzyme nitric oxide synthase mediates the production of nitric oxide. Three series of experiments were performed in rat and pig disc herniation models to (a) investigate nitric oxide synthase activity in spinal nerve roots after exposure to autologous nucleus pulposus and (b) evaluate the effects of systemic treatment with aminoguanidine, a nitric oxide synthase inhibitor, on vascular permeability and nerve-conduction velocity. In a disc herniation model in the rat, calcium-independent nitric oxide synthase activity was measured in nerve roots exposed to nucleus pulposus; however, no nitric oxide synthase activity was detected in nerve roots from animals that underwent a sham operation, reflecting increased inducible nitric oxide synthase activity. In nucleus pulposus-exposed spinal nerve roots in the pig, the edema was less severe after systemic aminoguanidine administration than without aminoguanidine treatment. Aminoguanidine treatment also significantly reduced the negative effect of nucleus pulposus on nerve-conduction velocity in spinal nerve roots in the pig. These results demonstrate that nucleus pulposus increases inducible nitric oxide synthase activity in spinal nerve roots and that nitric oxide synthase inhibition reduces nucleus pulposus-induced edema and prevents reduction of nerve-conduction velocity. Furthermore, the results suggest that nitric oxide is involved in the pathophysiological effects of nucleus pulposus in disc herniation.     

兔髓核与纤维环细胞生物学特性差异的研究

目的:同时建立兔髓核细胞与纤维环细胞体外培养模型,比较两者生物学特性差异。方法:新西兰大白兔5只(2～3kg,雌雄不限),无菌条件下分离髓核及纤维环,酶消化法联合组织块法含15%FBS的DMEM/F12(1∶1)培养液培养,当细胞90%融合后进行传代培养。通过倒置相差显微镜观测细胞形态,台盼蓝染色测定细胞活力,甲苯胺蓝和HE染色进行组织学观察,MTT法测定细胞增殖,分析比较髓核细胞与纤维环细胞形态、活力、增殖的差异。结果:原代及第1代髓核细胞和纤维环细胞形态上无明显差异,第2代髓核细胞开始有空泡出现。髓核细胞较纤维环细胞贴壁时间晚、细胞活力低;原代髓核细胞从第9天开始增殖速度较纤维环细胞慢(P<0.05)。结论:纤维环细胞的细胞活性明显高于髓核细胞。椎间盘退变性疾病可能是由髓核发生衰退引起,从而局部生物力学改变,导致纤维环破裂等组织结构的改变及功能的丢失。     

Nucleus pulposus-induced nerve root injury: effects of diclofenac and ketoprofen

MAIN PROBLEM: Nucleus pulposus and/or chronic compression can induce spinal nerve root injury. Inflammation has been proposed as having major importance in the pathophysiologic mechanisms involved in the induction of such injuries. Corticosteroids, potent anti-inflammatory drugs, have been demonstrated to reduce nucleus pulposus-induced spinal nerve root injury. The aim of the present study was to assess the effects of two potent non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac and ketoprofen, in experimental nucleus pulposus-induced spinal nerve root injury in a pig model. METHODS: Eighteen pigs were included in the study. Autologous nucleus pulposus was harvested from a lumbar disc and applied locally around the first sacral nerve root after a partial laminectomy of the first and second sacral vertebrae. Six pigs were treated with daily intramuscular injections of diclofenac, 3 mg/kg body weight, for 7 days. Six other pigs were treated with daily intramuscular injections of ketoprofen, 4 mg/kg body weight, for 7 days. As controls, six pigs received injections with physiologic saline. After 7 days, the pigs were reanesthetized and the nerve conduction velocity over the exposed nerve root area was determined. RESULTS: The nerve conduction velocity was significantly higher in pigs treated with diclofenac than in the saline-treated controls, (57 +/- 6 m/s vs 38 +/- 18 m/s, P<0.05, Student's t-test). The velocity in pigs treated with ketoprofen, 42 +/- 24 m/s, did not differ significantly from that of controls. CONCLUSIONS: This study of two potent NSAIDs indicates that nucleus pulposus-induced nerve root dysfunction may be reduced by diclofenac but not by ketoprofen. The reason for this difference is not known, but it might be related to the fact that ketoprofen and diclofenac belong to different NSAID subgroups and have a different selectivity for the two cyclo-oxygenases COX-1 and COX-2.     

The effect of age on inflammatory responses and nerve root injuries after lumbar disc herniation: an experimental study in a canine model

STUDY DESIGN: An experimental investigation on the effect of age on pathologic events surrounding the herniated disc and at the adjacent nerve root. OBJECTIVES: To investigate the role of age on the inflammatory responses and nerve root damage surrounding a sequestered lumbar disc fragment using a dog model. SUMMARY OF BACKGROUND DATA: Lumbar disc herniation is manifested in patients by variable clinical findings, natural history, and resorption phenomena in which the variability is particularly noted among patients with different ages. There are no previous reports on the effect of age on pathologic events induced by the herniated disc. METHODS: Six beagle dogs, including two animals of each age group of 6, 12, and 24 months (human equivalent ages of 10, 15, and 24 years), were used in this study. The dogs underwent L4-L5, L5-L6, and L6-L7 laminotomy and discectomy under general anesthesia. An autologous intervertebral disc from the tail was divided into anulus fibrosus and nucleus pulposus fragments. The anulus fibrosus and nucleus pulposus fragments were placed in the anterolateral epidural space of L5-L6 and L6-L7, respectively. The L4-L5 discectomy site served as a control. Dogs were killed at 12 weeks after surgery. The lumbar spine was removed en bloc, and histologic sections were prepared consecutively and examined. RESULTS: In the nucleus pulposus group at L6-L7, neovascularity, and intensive infiltration of lymphocytes, macrophages, and fibroblasts were observed surrounding the nucleus pulposus fragment in the 24-month-old group only. Degenerative changes of the nerve root fibers were observed in the 24-month-old group only. In the control and anulus fibrosus groups at L4-L5 and L5-L6, there were no marked inflammatory reactions in all age groups. The nerve root fibers around the anulus fibrosus were normal in all age groups. CONCLUSIONS: There is an effect of age on the inflammatory response and nerve root injury caused by the herniated disc. The apparent neuroprotective mechanism in the young animal, and the apparent inflammatory and resorption changes of the nucleus pulposus fragment in the older animal are quite intriguing.     

Alterations in the mechanical behavior of the human lumbar nucleus pulposus with degeneration and aging

This study tested the hypothesis that changes in the morphology and composition of the nucleus pulposus with age and degeneration have associated changes in its mechanical properties. A torsional shear experiment was used to determine viscoelastic shear properties of cylindrical samples of human nucleus pulposus with large ranges of grades of morphological degeneration (normal to severely degenerated) and ages (range: 16–88 years; average: 57 ± 21.5 years). Viscoclastic shear properties were determined from stress-relaxation and dynamic sinusoidal tests. A linear viscoelastic law with a variable-amplitude relaxation spectrum was used to model experimental behaviors of nucleus pulposus specimens. A statistically significant increase in the instantaneous and dynamic shear moduli was found with increasing age and grade of degeneration; the values for moduli ranged from 5.0 to 60 kPa. A significant decrease in tanδ was also detected; the values ranged from 0.43 to 0.33, indicating a decreased capacity for the nucleus pulposus to dissipate energy. The dynamic modulus and tanδ were also significantly affected by frequency. It was generally concluded that the nucleus pulposus undergoes a transition from “fluid-like” behavior to more “solid-like” behavior with aging and degeneration.     

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.     

Myxomatous degeneration of the lumbar intervertebral disc

Sixteen patients were operated on for lumbar pain and pain radiating into the sciatic nerve distribution. In all 16, when the anulus fibrosus was incised, soft, gray disc material extruded under pressure like toothpaste being squeezed from a tube. This syndrome of myxomatous degeneration is a distinct entity, different from classical fibrotic disc degeneration or herniated nucleus pulposus. Surgical removal associated with partial facetectomy produced excellent results. The concept of incompetence of the anulus fibrosis is discussed.     

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.     

Fibronectin and its fragments increase with degeneration in the human intervertebral disc

STUDY DESIGN: This laboratory-based experiment correlates fibronectin content of intervertebral disc with a morphologic grade of degeneration. OBJECTIVES: To correlate the fibronectin content of the anulus fibrosus and nucleus pulposus with a gross morphologic grade of disc degeneration, and to determine the molecular size of the extractable fibronectin. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration increases with age and can lead to low back pain. Fibronectin helps to organize the extracellular matrix and provides environmental cues by interaction with cell surface integrins. In other tissues, its synthesis is elevated in response to injury. Fibronectin fragments can stimulate cells to produce metalloproteases and cytokines and inhibit matrix synthesis. METHODS: In this study, 17 anuli fibrosis and 18 nuclei pulposus from 11 spines were graded by Thompson's gross morphologic scale. Fibronectin was sequentially extracted with 4 mol/L guanidine hydrochloride and trypsin, and then quantitated by enzyme-linked immunoassay. The size of extractable fibronectin was determined by Western blot analyses. RESULTS: The fibronectin content of the disc increased with grade and was significantly elevated between Grades 3 and 4. The percentage of extractable fibronectin varied widely, but it was more extractable from the nucleus. In both the nucleus and anulus, 30% to 40% of the extractable fibronectin existed as fragments. Many of the fragments contained functional heparin or collagen-binding sites. CONCLUSIONS: Fibronectin is elevated in degenerated discs and frequently present as fragments. Elevated levels of fibronectin suggest that disc cells are responding to the altered environment. Fibronectin fragments resulting from normal or enhanced proteolytic activity could be a mechanism that induces the cell to degrade the matrix further.     

Contribution of disc degeneration to osteophyte formation in the cervical spine: a biomechanical investigation.

Cervical spine disorders such as spondylotic radiculopathy and myelopathy are often related to osteophyte formation. Bone remodeling experimental-analytical studies have correlated biomechanical responses such as stress and strain energy density to the formation of bony outgrowth. Using these responses of the spinal components, the present study was conducted to investigate the basis for the occurrence of disc-related pathological conditions. An anatomically accurate and validated intact finite element model of the C4-C5-C6 cervical spine was used to simulate progressive disc degeneration at the C5-C6 level. Slight degeneration included an alteration of material properties of the nucleus pulposus representing the dehydration process. Moderate degeneration included an alteration of fiber content and material properties of the anulus fibrosus representing the disintegrated nature of the anulus in addition to dehydrated nucleus. Severe degeneration included decrease in the intervertebral disc height with dehydrated nucleus and disintegrated anulus. The intact and three degenerated models were exercised under compression, and the overall force-displacement response, local segmental stiffness, anulus fiber strain, disc bulge, anulus stress, load shared by the disc and facet joints, pressure in the disc, facet and uncovertebral joints, and strain energy density and stress in the vertebral cortex were determined. The overall stiffness (C4-C6) increased with the severity of degeneration. The segmental stiffness at the degenerated level (C5-C6) increased with the severity of degeneration. Intervertebral disc bulge and anulus stress and strain decreased at the degenerated level. The strain energy density and stress in vertebral cortex increased adjacent to the degenerated disc. Specifically, the anterior region of the cortex responded with a higher increase in these responses. The increased strain energy density and stress in the vertebral cortex over time may induce the remodeling process according to Wolff's law, leading to the formation of osteophytes.     

实验性颈椎动力平衡失调后髓核超微结构观察

目的 探讨颈椎动平衡失调对椎间盘髓组织超微铁影响,方法 选择ＳＤ大鼠２４只,随机分为４组,手术切除大鼠颈背部浅肌群、深肌群、全肌群、建立颈椎不同程度动力平衡失调的实验模型,２、４、６个月后动态观察颈椎间盘髓组织内细胞超微结构变化,并与正常对照组相比较。结果 颈椎动力平衡失调一髓核组织内细胞退变、坏死加速加重,以全肌群损伤组最为明显,浅肌群损伤组次之,深肌群损伤组较轻。结论 颈椎动力平衡调失可加速颈     

Creation of an injectable in situ gelling native extracellular matrix for nucleus pulposus tissue engineering

Background Context

Disc degeneration is the leading cause of low back pain and is often characterized by a loss of disc height, resulting from cleavage of chondroitin sulfate proteoglycans (CSPGs) present in the nucleus pulposus. Intact CSPGs are critical to water retention and maintenance of the nucleus osmotic pressure. Decellularization of healthy nucleus pulposus tissue has the potential to serve as an ideal matrix for tissue engineering of the disc because of the presence of native disc proteins and CSPGs. Injectable in situ gelling matrices are the most viable therapeutic option to prevent damage to the anulus fibrosus and future disc degeneration.

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。     

False-negative lumbar discograms. Correlation of discographic and histological findings in postmortem and surgical specimens

To investigate the causes of false-negative discograms, 181 lower thoracic and lumbar intervertebral discs that had been removed as part of en bloc specimens during thirty autopsies were studied first by discography and then histologically. Comparison of the results of the two methods showed that if fissures and cysts were present in a degenerated anulus fibrosus, but did not establish continuity between the nuclear cavity and the site of a herniation, the discogram was false-negative. Under these circumstances, the inner fiber bundles of the anulus fibrosus were intact and their orientation was often reversed, so that they bulged inward. This finding suggested that a protrusion or a prolapse of tissue from just the anulus fibrosus might have been developing. Ten of the fifty-seven discs that had such changes in the orientation of the fibers had a histologically proved protrusion or prolapse of the anulus fibrosus. However, the discograms showed protrusion in only six of the ten discs and demonstrated a false-negative result in the other four. The cases of seventy-seven patients in whom discography had been performed and a herniation had been subsequently confirmed at operation were also studied. Fifty-nine of the patients had a protrusion and eighteen had a prolapse of the disc. The discograms were falsely interpreted as negative in 32 per cent (nineteen) of the fifty-nine patients who had a protrusion and in 56 per cent (ten) of the eighteen who had a prolapse. Histologically, the prolapses were interpreted as protrusions of a portion of the anulus fibrosus. It was concluded that false-negative discograms are more frequent when a protrusion or a prolapse involves the anulus fibrosus rather than the nucleus pulposus, and that a negative discogram does not exclude the possibility of extensive degeneration of the anulus fibrosus.     

Comparison of neuropathic pain induced by the application of normal and mechanically compressed nucleus pulposus to lumbar nerve roots in the rat.

We studied whether applying nucleus pulposus tissue, obtained from tail intervertebral discs that had been subjected to chronic mechanical compression, to the lumbar nerve roots produces hyperalgesia, which is thought to be a pain-related behavior in the rat. An Ilizarov-type apparatus was used for immobilization and chronically applied compression of the rat tail for eight weeks. Three weeks after application of extracted nucleus pulposus tissue on the lumbar nerve roots, motor function, sensitivity to noxious mechanical stimuli was measured. Eight weeks after application of the apparatus, the instrumented vertebrae were resected and sections were stained with hematoxylin and eosin to evaluate degeneration of the intervertebral disc. Mechanical hyperalgesia observed in rats treated with the compressed nucleus pulposus tissue was greater and of longer duration than in the rats treated with normal and non-compressed discs. The nucleus pulposus in the instrumented vertebrae showed some histological degeneration. In conclusion, chronic mechanical compression of nucleus pulposus, which resulted in degeneration to some extent, enhanced mechanical hyperalgesia, which was induced by application of nucleus pulposus on the nerve root in the rat. Degenerative intervertebral discs might induce more significant pain than normal intervertebral discs.