Expression of Fas ligand and apoptosis of disc cells in herniated lumbar disc tissue

STUDY DESIGN: An examination of surgically obtained herniated lumbar disc tissues performed by using immunohistochemical staining and the DNA nick end labeling method. OBJECTIVE: To investigate the cell type that expresses Fas ligand (FasL) and any evidence of apoptosis of the disc cells in herniated lumbar disc tissues. SUMMARY OF BACKGROUND DATA: The Fas/FasL system is involved in delivering a death signal that rapidly commits the cells to apoptosis. In the authors' previous study, the expression of Fas on disc cells was identified in herniated lumbar disc tissue. METHODS: Twenty-three herniated lumbar disc tissues (contained disc, n = 9; noncontained disc, n = 14) were examined to investigate the cell type that expresses FasL and any evidence of apoptosis of the disc cells by using immunohistochemical staining and the DNA nick end labeling method, respectively. The percentage of FasL-positive disc cells was calculated and compared with clinical and radiologic data. RESULTS: FasL was expressed in the cytoplasm of the disc cells, and nuclear DNA fragmentation in a few disc cells was identified. A higher degree of FasL expression in disc cells was found in noncontained discs than in contained discs (P < 0.05). The percentage of FasL-positive disc cells significantly increased with the patient's age (P < 0.05), but not with the degree of disc degeneration (P > 0.05). CONCLUSION: The current results indicate that disc cells, after herniation, undergo apoptotic cell death via autocrine or paracrine FasL mechanisms by the disc cells themselves.     

Types of lumbar herniated disc and clinical course

STUDY DESIGN: A retrospective study of different types of herniated discs and duration of symptoms in patients with lumbar disc herniation, and a trial of longer conservative treatment to reduce the number of operations. OBJECTIVE: To determine whether noncontained and contained herniated discs have different clinical courses and to evaluate the results of the clinical trial of longer and vigorous conservative treatment. SUMMARY OF BACKGROUND DATA: The possibility of a difference in clinical features between contained and noncontained disc herniation has been suggested previously. METHODS: In the first study, the medical history and intraoperative findings of 156 patients who had undergone herniotomy were reviewed. In the second study, conservative treatment of at least 2 months' duration was recommended for all patients with lumbar disc herniation. RESULTS: In the first study, patients with noncontained disc herniation had a shorter preoperative clinical course than those with contained disc herniation. It was rare for noncontained herniation to require surgery 4 months or more after the onset of symptoms. In the second study, the authors' protocol reduced the number of herniotomies required, especially the number of operations for the patients with noncontained disc herniation. CONCLUSIONS: The authors believe that patients with noncontained lumbar disc herniation can be treated without surgery, if these patients can tolerate the symptoms for the first 2 months.     

腰椎间盘突出症突出髓核中抗原抗体复合物测定的临床意义

目的：探讨抗原体复合物在突出髓核中的分布及临床意义。方法：应用免疫酶组织化学染色的方法，对31例腰椎间盘突出症患的突出髓核中抗原抗体复合物进行检测，与20例正常椎间盘作对照并结合临床资料分析其意义。结果：在突出髓核的标本中可在髓核细胞膜周围观察到显示阳性的棕色沉淀物存在，而在正常椎间盘对照组中却未见阳性显示。突出型及脱垂游离型髓核中68．42％显示为强阳性，31．58％显示为阳性，膨隆型髓核中58．33％显示为阳性，41．67％显示为阴性。两组之间P＜0．05，有统计差异。结论：在突出髓核组织普遍存在抗原体复合物，而健康椎间盘中却不含有此免疫复合物。抗原体复合物阳性与强阳性表达与髓核暴露于机体免疫系统的程度相关，临床疼痛症状的程度与自身免疫反应的程度相关。髓核突出后引起的自身免疫反应是导致神经根慢性炎症的重要原因。     

Transforming growth factor β receptor induction in herniated intervertebral disc tissue: an immunohistochemical study

Transforming growth factor beta (TGF-beta) is a potent inducer of angiogenesis and fibrogenesis. There is presently little information about the pathophysiological function of TGF-beta in herniated disc tissue. In order to analyze the cellular role and activation of TGF-beta after disc herniation we immunostained frozen material from 38 disc herniation operations and from eight macroscopically normal discs from organ donors. Polyclonal TGF-beta-I, TGF-beta-II and TGF-beta receptor type II antibodies were used with the avidin biotin complex (ABC-) immunoperoxidase method. All the herniated discs were TGF-beta immunopositive. Such immunoreactivity was mainly associated with disc cells. In a few samples, capillaries were also TGF-beta immunopositive. Immunopositivity was similarly observed in the control discs. To analyze possible differences between the two groups, we calculated the ratio of immunopositive disc cells. For all three antibodies, a statistically significantly (Mann-Whitney test, P = 0.0001) higher number of disc cells showed immunopositivity in the herniated discs. The increase in TGF-beta receptor immunopositivity suggested induction of TGF-beta receptors in herniated discs. Our results support an active regulatory role for TGF-beta in disc cell metabolism.     

腰椎间盘中血管内皮生长因子的表达及其意义

目的 :观察并探讨腰椎间盘中内源性血管内皮生长因子 (vascularendothelialgrowthfactor,VEGF)的表达分布规律及其意义。方法 :采用免疫组织化学技术检测 1 6例胎儿期、8例生长期、1 2例成熟退变期和 42例突出椎间盘中VEGF的表达。结果 :胎儿椎间盘脊索细胞和纤维环外层血管内皮细胞出现阳性免疫染色 ,阳性率为 87 5 % ;生长期和成人期椎间盘未见阳性表达 ;退变突出组总阳性率为 83 3 %。VEGF表达主要出现于破裂型和游离型椎间盘突出 (P <0 0 1 ) ,其细胞来源主要是突出椎间盘组织中毛细血管内皮细胞、髓核内的类软骨细胞及单核巨噬细胞。年龄与VEGF表达阳性率关系不大 (P >0 0 5)。病程超过 1年者VEGF阳性率明显低于 1年以内者 (P <0 0 5)。结论 :胎儿期和破裂型 (包括游离型 )突出椎间盘组织可产生内源性VEGF ,突出椎间盘中VEGF的阳性表达与病程、突出类型密切相关     

前列腺素E2在突出腰椎间盘中的表达及其与坐骨神经痛的关系

目的探讨前列腺素(PG)E2在突出腰椎间盘组织中的表达及其在坐骨神经痛发病机制中的作用。方法 42个突出椎间盘标本取自42例腰椎间盘突出并有坐骨神经放射性疼痛症状的手术治疗患者,其中膨隆型12例,破裂型15例,游离型15例,取材部位为紧贴神经根突入椎管的椎间盘组织(A部位)和椎间隙内残存的椎间盘组织(B部位)。术前采用视觉模拟评分(VAS)对所有患者坐骨神经痛严重程度进行评分。应用酶联免疫吸附试验(ELISA)检测PGE2含量。结果 A部位PGE2含量自膨隆型、破裂型至游离型逐渐升高,差异有显著性(P<0.01);A部位PGE2含量高于B部位(P<0.01);PGE2含量与患者坐骨神经痛VAS评分存在明显相关性(r=0.848,P<0.01)。结论 PGE2参与了腰椎间盘退变、突出的发病机制,PGE2含量与坐骨神经痛程度呈正相关性。     

Herniation of cervical intervertebral disc: immunohistochemical examination and measurement of nitric oxide production.

STUDY DESIGN: Surgically obtained cervical herniated intervertebral discs were examined histologically and immunohistochemically. The production of nitric oxide (NO) in the local tissue was examined using the electron spin resonance (ESR) method. OBJECTIVES: To investigate the local histologic and immunohistochemical changes in cervical disc herniation, including NO production, and to compare such changes with those in autopsy cases. SUMMARY OF BACKGROUND DATA: Very little is known about the histopathologic processes of cervical disc herniation. In addition, no information is available on the level of in vivo NO production in cervical disc herniation. METHODS: Thirty-six herniated cervical discs obtained from 31 patients were immunohistochemically examined for localization of blood vessels, matrix metalloproteinase (MMP)-3, and inducible NO synthetase (iNOS). We also compared the production of NO, measured by the ESR method, in eight specimens with that of five control discs obtained from fresh cadavers. RESULTS: The presence of herniated discs correlated with the degeneration of cartilaginous endplate and torn anulus fibrosus. Formation of new blood vessels around the herniated discs was detected, using von Willebrand factor antibody, in seven uncontained hernias and 20 contained hernias. Immunohistochemical studies showed the presence of cells positive for MMP-3 (chondrocytes), iNOS (chondrocytes and granulation tissue) in cervical disc hernias. ESR analysis showed a significantly higher NO production in herniated cervical discs than in disc samples of fresh cadavers. CONCLUSIONS: Herniated cervical intervertebral disc is characterized by the presence of an inflammatory process associated with neovascularization and increased expression of MMP-3. Production of NO was markedly high in both contained- and uncontained-type hernias.     

Relationship between neovascularization and degenerative changes in herniated lumbar intervertebral discs

Purpose

Lumbar disc degeneration may be associated with intensity of neovascularization in disc herniations. Our study was designed to evaluate how much the severity of histodegeneration is related to the development of neovascularization and to the level of pleiotrophin in the herniated lumbar discs.

Methods

Surgically excised lumbar disc specimens were obtained from 29 patients with noncontained (i.e., extruding through the posterior longitudinal ligament) and 21 patients with contained disc herniations. The histodegeneration scores and levels of neovascularization were estimated according to semiquantitative analysis in lumbar disc and endplate samples. Immunohistochemical staining were performed to identify the newly formed blood vessels and to detect the presence of pleiotrophin in the specimens.

Results

Higher levels of disc and endplate neovascularity were registered in noncontained herniations. The level of neovascularization was significantly related to the score of histodegeneration in the herniated disc tissues but not in the endplate specimens. Both contained and noncontained herniations had the highest values of histodegeneration in conjunction with the highest level of neovascularization but the relations between neovascularity and degenerative changes remained to be significant only in the group of noncontained herniations. Registration or frequency of pleiotrophin positive cells did not correlate significantly with histodegeneration or level of neovascularization in the disc samples.

Conclusion

Severe histodegeneration of the lumbar disc herniations is associated with enhanced neovascularization and potentially also spontaneous regression of the herniated tissue.     

Immunohistological study of intervertebral disc herniation of lumbar spine

In order to observe histological changes in the extruded and sequestrated intervertebral disc, we conducted pathological and immunological examinations of herniated disc materials taken at the time of discectomy. There were 49 disc materials (from 38 men and 10 women [aged 19 to 78 years; average, 36.6 years]). The herniation was classified into four types, based on the intraoperative observations: protrusion (P), subligamentous extrusion (SE), transligamentous extrusion (TE), and sequestration (S). There were 19 P type discs, 3 SE type, 10 TE type, and 17 S type. The surgical specimens were stained with hematoxylin-eosin, as well as immunohistological staining with the labelled streptavidin biotin method, using human T-cell , human B-cell, and human macrophage antibodies. Inflammatory-cell infiltration was observed at the border of the disc. These findings were present in 19 discs (70%) of the 27 discs of TE and S types (10 TE and 17 S types), but were not seen in the 22 discs of P and SE types (19 P and 3 SE types). Immunohistological staining of the area with inflammatory-cell infiltration revealed the presence of T cells and macrophages, which suggested that this cell infiltration originated from T cells and macrophages, and that the spontaneous resorption of the disc may have resulted from the phagocytic activities of these cells. Received for publication on June 1, 1998; accepted on Nov. 8, 1999     

一氧化氮在突出腰椎间盘中的表达及其意义

目的 :研究一氧化氮 (NO)在突出腰椎间盘组织中的含量及组织学定位 ,并对其意义进行探讨。方法 :对 32例腰椎间盘突出患者的突出间盘组织采取两种方法进行研究 :(1) 12例做体外培养 ,用分光光度法测定培养液上清中NO含量 ;(2 ) 2 0例用免疫组化方法对产生NO的细胞类型及组织学定位进行研究。同时对取自 4具新鲜尸体的 12个正常椎间盘采用相同方法做为对照。结果 :突出腰椎间盘组织产生NO的量为 2 0 0 70± 6 5 5 5nmol/g ,正常对照组的NO量为 76 31± 19 49nmol/ g ,两者统计学有显著性差异 (P <0 0 0 1)。免疫组化结果发现 ,2 0例患者椎间盘组织中一氧化氮合成酶表达阳性 16例 ,12个正常椎间盘组织中无表达阳性细胞。结论 :诱导型一氧化氮合成酶主要由突出椎间盘周围的肉芽组织产生 ,阳性细胞主要以成纤维细胞、软骨细胞及淋巴细胞为主。腰椎间盘可自身合成NO ,NO可能在椎间盘退变中起重要作用 ,突出腰椎间盘中的NO主要由突出腰椎间盘周围的肉芽组织产生。     

Facet tropism: a comparison between far lateral and posterolateral lumbar disc herniations

STUDY DESIGN: An assessment of the difference in the degree of facet tropism and disc degeneration between far lateral and posterolateral lumbar disc herniations. OBJECTIVE: To investigate the effect of the difference in the degree of the facet tropism and disc degeneration with respect to the development of far lateral lumbar disc herniation and posterolateral lumbar disc herniation, and to compare the effect between the two types of herniations. SUMMARY OF BACKGROUND DATA: The effect of facet tropism on the development of posterolateral lumbar disc herniation has been investigated previously, but there has been no study on far lateral lumbar disc herniation. METHODS: Thirty-eight lumbar disc herniations (far lateral, n = 19; posterolateral, n = 19) were included this study. The degree of facet tropism and disc degeneration was measured at the herniated disc level by using magnetic resonance imaging. The results were compared to show any differences between the two types of lumbar disc herniations. RESULTS: There were significant differences in the degree of facet tropism (24.74 vs. 14.26, P = 0.004) and disc degeneration (23.92 vs. 15.08, P = 0.005) between the far lateral and posterolateral lumbar disc herniations. There was no significant correlation between the degree of facet tropism and the degree of disc degeneration in far lateral lumbar disc herniation (r = -0.369, P = 0.120). CONCLUSION: This results suggest that the differences in the degree of facet tropism and disc degeneration might be considered a key factor in distinguishing the development of far lateral lumbar disc herniation from that of posterolateral lumbar disc herniation.     

Influence of macrophage infiltration of herniated disc tissue on the production of matrix metalloproteinases leading to disc resorption.

STUDY DESIGN: Herniated lumbar disc specimens were cocultured with peripheral blood mononuclear cells, and cells isolated from extruded disc were cultured to study the production of matrix metalloproteinases. OBJECTIVE: To investigate the role of peripheral blood mononuclear cells infiltrating extruded discs and disc-derived cells in the production of matrix metalloproteinases. SUMMARY OF BACKGROUND DATA: Magnetic resonance imaging analysis of herniated disc patients revealed a progressive decrease in the size of herniated discs. Spontaneous regression of herniated disc is associated with infiltrating macrophages, and matrix metalloproteinases have been implicated in this phenomenon. However, the correlation between infiltrating macrophages and the production of matrix metalloproteinases has received little research attention. METHODS: Each disc specimen was incubated with homologous peripheral blood mononuclear cells. The numbers of peripheral blood mononuclear cells attached to the surfaces of herniated discs were counted and the culture media was assayed for MMP-3. The cells isolated from herniated discs were incubated with cytokines and the production of matrix metalloproteinases was measured. Total RNA was extracted from herniated discs and RT-PCR was carried out. RESULTS: Significantly larger numbers of peripheral blood mononuclear cells were attached to the surfaces of extruded discs, and higher amounts of MMP-3 were detected than those of control discs. The culture medium of extruded discs showed higher MMP-1 and MMP-3 production than those from controls. Significant enhancement of MMP-1 and MMP-3 mRNA expression was observed in the disc-derived cells stimulated with cytokines. CONCLUSION: These results suggest that peripheral blood mononuclear cells infiltrating extruded discs may secrete a variety of biologic materials capable of further recruiting monocytes into herniated discs in an autocrine fashion. Disc cells stimulated with cytokines showed enhanced production of matrix metalloproteinases, which might play an important role in spontaneous regression of disc materials.     

腰椎间盘突出症的免疫病理学研究

目的从免疫组织化学角度研究破碎型和完整型腰椎间盘突出症的病理机制和病理过程，比较其差异，探讨腰椎间盘突出症的不同病理学分型。方法选取40例腰椎间盘突出症患者的椎间盘手术标本，依术中所见分为两组：（1）破碎型腰椎间盘突出组（切开突出病变部浅层后纵韧带及纤维环可见破碎椎间盘组织与椎间盘母体分离，突出病变质软，自行溢出或较易钳出）。（2）完整型腰椎间盘突出组（切开突出病变部浅层后纵韧带及纤维环无破碎椎间盘组织溢出，突出病变质硬，必须以器械切除）。所获得的椎间盘标本均行常规HE染色；以鼠抗人CD43RO、CD20单克隆抗体进行免疫组织化学标记，双盲法半定量计数阳性细胞，Ridit等级分析；以FITC标记的兔抗人IgM、IgG抗体进行免疫荧光标记，双盲法半定量计数荧光量，Ridit等级分析。结果两组形态学有显著差异：（1）HE染色可见破碎组标本边缘灶性炎性细胞浸润，血管化；完整组髓核面积减少，纤维环增厚，软骨基质增生；（2）破碎组标本CD。sRO免疫组织化学阳性反应与完整组比较差异有统计学意义（P〈0．05）；（3）破碎组标本IgG和kM免疫荧光阳性反应与完整组比较差异有统计学意义（P〈0．01）。结论（1）破碎型腰椎间盘突出症标本中有T淋巴细胞浸润和免疫球蛋白IgG、IgM沉积，因而其病理机制可能是在损伤基础上的自免疫炎症反席过程。（2）完整犁腰椎间鼎突出以髓核很蛮、软骨某质及纤维环增牛为丰兽表现．     

磷脂酶A_2活性异常升高可能是腰椎间盘突出症疼痛重要病因

目的 :探讨腰椎间盘突出症疼痛的可能病因。方法 :用微量酸滴定法测定椎间盘、黄韧带和硬膜外脂肪中 PL A2 活性。结果 :腰椎间盘突出症患者椎间盘、黄韧带和硬膜外脂肪中 PL A2 活性升高均有显著性意义 (三者 P均 <0 .0 0 1)且三者间均有相关性 (r椎 ,黄 =0 .6 86 3,P=0 .0 0 1;r=椎 ,硬 =0 .7388,P<0 .0 0 1;r黄 ,硬 =0 .6 113,P<0 .0 0 5 )。结论 :椎间盘退变的病理变化不仅发生在椎间盘本身 ,还涉及到同一节段的黄韧带和硬膜外脂肪 ,可能是它们中活性异常升高的 PL A2 共同作用神经根而致痛的。     

Biochemical and morphological changes in herniated human intervertebral disc

The molecular and morphologic features of herniated human intervertebral disc tissues are of particular importance to clarify the pathogenesis. The present study analyzed the biochemical and morphological features of herniated intervertebral disc tissues to determine the constituent factors responsible for intervertebral disc herniation. A total of 32 herniated disc specimens and 4 control disc samples were analyzed. Collagen subunit composition, collagenase activity, lipid peroxidation level, caspase-3 activity, metal levels, morphologic studies, and genetic analysis were performed on herniated disc tissues of chronic (group A) and acute (group B) group and compared with findings of control group. Nick translation analysis in situ revealed apoptotic-positive stained DNA fragments as black-brown spots in herniated disc tissues. The presence of type II collagen in control disc samples and its absence in herniated samples were confirmed immunohistochemically. The increased caspase-3 activity, the apoptotic-positive stained DNA fragments, and the electron microscopic findings suggest enhanced programmed cell death in herniated discs. The significant increase in lipid peroxidation levels and collagenase activity, and the low metal levels suggest the enhancement of cell death signals in herniated discs, caused by oxygen stress. Linkage analysis of herniated disc tissues in Japanese individuals may suggest ethnic variation. These findings may be helpful in understanding the pathogenesis of herniated disc disease. Received: November 27, 2000     

腰椎间盘突出CT扫描三维定位诊断

目的：研究椎间盘突出的三维定位,为腰椎间盘突出患者提供更精确的诊断依据。方法：对40例椎间盘突出CT扫描后进行多平面重建,得到矢状位图像。用1－4四个数字代表突出髓核在横断位上的位置,在横断位或矢状位上测量髓核后突的程度,在矢状位上测量髓核上下移位的长度。按照左右、前后、上下的顺序来描述髓核突出的部位、后突程度和长度,并与手术结果对照。结果：三维定位提供的部位、程度和长度与手术结果相符。结论：多平面重建图像和三维定位方法是可靠的,可为椎间盘突出的诊断提供更精确可靠的依据。     

Herniated and spondylotic intervertebral discs of the human cervical spine: histological and immunohistological findings in 500 en bloc surgical samples. Laboratory investigation

OBJECT: In this paper the authors' goal was to identify histological and immunohistochemical differences between cervical disc hemrniation and spondylosis. METHODS: A total of 500 cervical intervertebral discs were excised from 364 patients: 198 patients with disc herniation and 166 patients with spondylosis. We examined en bloc samples of endplate-ligament-disc complexes. Types of herniation and graded degrees of disc degeneration on MR images were examined histologically and immunohistochemically. RESULTS: The herniated discs showed granulation tissue, newly developed blood vessels, and massive infiltration of CD68-positive macrophages, which surrounded the herniated tissue mainly in the ruptured outer layer of the anulus fibrosus. The vascular invasion was most significant in uncontained (extruded)-type herniated discs. Chondrocytes positive for matrix metalloproteinase (MMP)-3, tumor necrosis factor (TNF)-alpha, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were abundant in both herniated and spondylotic discs. Free nerve fibers, positive for nerve growth factor (NGF), neurofilament 68, growth-associated protein (GAP)-43, and substance P, were strongly apparent in and around the outer layer of uncontained (extruded)-type herniated discs, with enhanced expression of NGF. The authors observed that herniated discs showed more advanced degeneration in the outer layer of the anulus fibrosus around the granulation tissue than spondylotic discs. On the other hand, spondylotic discs showed more advanced degeneration in the cartilaginous endplate and inner layer of the anulus fibrosus than herniated discs. Spondylotic discs also had thicker bony endplates and expressed TNFalpha and MMP-3 more diffusely than herniated discs, especially in the inner layer of the anulus fibrosus. CONCLUSIONS: The authors' results indicate that herniated and spondylotic intervertebral discs undergo different degenerative processes. It is likely that TNFa, MMP-3, bFGF, and VEGF expression is upregulated via the herniated mass in the herniated intervertebral discs, but by nutritional impairment in the spondylotic discs. Macrophage accumulation around newly formed blood vessels in the herniated disc tissues seemed to be regulated by MMP-3 and TNFalpha expression, and both herniated and spondylotic discs exhibited marked neoangiogenesis associated with increased bFGF and VEGF expression. Nerve fibers were associated with NGF overexpression in the outer layer of the anulus fibrosus as well as in endothelial cells of the small blood vessels.     

Effect of the transligamentous extension of lumbar disc herniations on their regression and the clinical outcome of sciatica

STUDY DESIGN: Magnetic resonance imaging of symptomatic herniated lumbar discs was investigated longitudinally and prospectively for the presence of tear in the posterior longitudinal ligament (PLL). OBJECTIVES: To clarify the effect of transligamentous extension through the PLL of herniated disc on its regression and to determine the factors contributing to a successful clinical outcome. SUMMARY OF BACKGROUND DATA: Greater regression of the herniated fragment has been noted with larger initial disc herniations. The exposure of herniated disc materials to the epidural vascular supply through the ruptured PLL has been suspected to play a part in the mechanism of disappearance of the herniated nucleus pulposus. However, it had not been shown clinically. METHODS: Clinical outcomes and magnetic resonance images of 36 patients with symptomatic lumbar disc herniations, treated conservatively, were analyzed. Patients were divided into three groups: subligamentous, transligamentous, and sequestered herniations. The size of the herniated disc was measured by herniation ratio, which is defined as the ratio of the area of herniated disc to that of the thecal sac on the axial view. Factors associated with the natural regression of herniated disc and the successful clinical outcome were explored. RESULTS: Of the 36 herniated discs, 25 decreased in size. Ten (56%) of 18 subligamentous herniations, 11 (79%) of 14 transligamentous herniations, and all 4 (100%) sequestered herniations were reduced in size. The average decreases in herniation ratio of the subligamentous, transligamentous, and sequestered disc groups were 17%, 48%, and 82% respectively. The decrease in herniation ratio was related to the presence of transligamentous extension but was not related to the initial size of herniation. Successful outcome correlated with a decrease in herniation of more than 20%. CONCLUSION: Transligamentous extension of herniated disc materials through the ruptured PLL is more important to its reduction in size than is the initial size of the herniated disc. Decrease in herniation ratio of more than 20% seems to correspond to successful clinical outcome.     

Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine

Nerve root irritation induced by factors produced by the intervertebral disc may play a crucial role in the pathophysiology of sciatic pain production. In this study we used immunohistochemistry to investigate the presence of transforming growth factor-beta1 (TGF-beta1), insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6), IL-6-receptor (IL-6R) and fibronectin in lumbar disc bioptic specimens from 30 patients with disc herniation (protrusion type). Chondrocytes of herniated discs stained positive for TGF-beta1, IGF-1, IL-6 and fibronectin. We demonstrated for the first time the presence of IL-6-R in the chondrocytes of herniated tissue. Specimens from autoptic healthy tissue were used as controls. In these sections no immunoreaction for TGF-beta1, IL-6, or IL-6R was found, while they expressed IGF-1 and fibronectin, but in lower quantities than herniated discs. These results demonstrated the production of factors such as TGF-beta1, IGF-1, IL-6, IL-6R and fibronectin at the site of lumbar disc herniation.     

The role of mast cells in disc herniation inflammation.

STUDY DESIGN: A study of herniated lumbar disc tissue samples and control disc material to determine the presence of mast cells in disc herniations. OBJECTIVES: To analyze whether mast cells have any involvement in disc herniation pathophysiology and lumbar pain, because mast cells may have an important role in acute and chronic inflammatory responses. SUMMARY OF BACKGROUND DATA: Studies of inflammatory cells, biochemical mediators of inflammation, and tissue degrading enzymes have suggested that these factors may be involved--and perhaps play an important role--in the pathophysiology of lumbar pain and radiculopathy. Mast cells are known to play an important role in acute and chronic inflammatory responses. It was therefore of interest to clarify their possible role in intervertebral disc herniation inflammation. METHODS: Fifty herniated lumbar discs from 50 patients who had undergone disc surgery and three normal control discs were obtained. Sections from every disc then were examined histologically and immunocytochemically for mast cells by using monoclonal antibodies to either of two types of specific proteases of mast cells, tryptase and chymase. RESULTS: By none of the methods could any mast cells be observed in any of the control disc samples. With toluidine blue staining, mast cells were observed in 9 of 50 (18%) of discs. Mast cells immunoreactive to either tryptase or chymase were observed in 10 of 50 disc samples (20%) and immunoreactive for tryptase and chymase simultaneously in 4 of 50 disc samples (8%). However, the majority of the samples studied (80%) demonstrated immunoreactivity to neither tryptase nor chymase. Among the samples studied were five disc protrusions that totally lacked mast cells. CONCLUSIONS: A minority of disc herniations exhibited mast cells, as verified by toluidine blue staining and immunocytochemistry. The results may suggest a role of mast cells in intervertebral disc herniation inflammation, but only in a subset of these cases. Massive infiltration by mast cells never was observed.