肥大细胞和巨噬细胞在疼痛椎间盘的分布和意义

目的研究肥大细胞和巨噬细胞在疼痛椎间盘的分布并探讨其与椎间盘退变的关系。方法收集腰椎后路切除的15个椎间盘源性下腰痛病人的21个通过腰椎间盘造影术证实的疼痛椎间盘,同时收集16个在M RIT2加权上信号强度明显减弱的无腰痛症状的生理老化椎间盘和10个正常对照椎间盘,行组织学检查并用免疫组化方法观察肥大细胞和巨噬细胞在不同椎间盘的分布。结果免疫组织化学结果显示在疼痛椎间盘的肉芽组织区有大量的肥大细胞和巨噬细胞分布,在肉芽组织邻近区有少量分布,在非肉芽组织区、生理老化椎间盘和正常对照椎间盘没有分布。结论研究结果提示肥大细胞和巨噬细胞在纤维环外层损伤后激发的炎症反应和随之的椎间盘退变过程中起关键作用。     

椎间盘退变过程中碱性成纤维细胞生长因子和转移生长因子-β1的表达及其意义

目的：研究椎间盘退变过程中碱性成纤维细胞生长因子(bFGF)和转移生长因子-β1(TGF-β1)的表达及其意义。方法：收集腰椎后路手术切除的15例椎间盘源性下腰痛患者的21个通过腰椎间盘造影术证实的疼痛椎间盘，同时收集16个在MRIT2加权像上信号强度明显减弱的无腰痛症状的生理老化椎间盘和10个正常对照椎间盘，行组织学检查并用免疫组化方法检测bFGF、TGF-β1及其受体在不同椎间盘组织中的表达，观察增殖细胞核抗原在不同椎间盘的表达。结果：免疫组化染色显示bFGF、TGF-β1及其受体在疼痛椎间盘大量表达，生理老化椎间盘有少量表达，正常对照椎间盘没有表达。增殖细胞核抗原在疼痛椎间盘的肉芽组织区大量表达，在非肉芽组织区有少量表达；生理老化椎间盘有少量表达，正常对照椎间盘组织没有表达。结论：椎间盘退变和椎间盘源性下腰痛起源于椎间盘纤维环的损伤修复过程，bFGF、TGF-β1在纤维环外层的损伤修复和随之的椎间盘退变过程中可能起关键作用。     

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。     

椎间盘源性腰痛

腰椎间盘已被认为是下腰痛的主要起源部位.椎间盘源性腰痛不涉及由腰椎间盘突出引起的腰腿痛,它指由腰椎间盘自身内部结构的变化引起的腰痛,椎间盘外部结构是正常的,它的病理学特征是通过纤维环的放射性裂隙和随之的血管化肉芽组织和疼痛神经纤维沿着撕裂长人的组织修复过程.临床研究表明椎间盘源性下腰痛占慢性下腰痛的39%,它是慢性下腰痛的主要类型.虽然仍有一些争议,腰椎间盘造影术是目前诊断椎间盘源性腰痛和确定损伤椎间隙水平的的最重要手段和方法,它的关键特点是病人对椎间盘刺激的主观反应,而不是椎间盘的外观结构.外科治疗椎间盘源性下腰痛一直是脊柱外科领域有争议的课题.无疑,对于大多数椎间盘源性下腰痛病人来说,保守治疗可能是有效的方法.但对于一些渐进发展的慢性失能性椎间盘源性下腰痛病人,通过各种非手术方法治疗无效的,仍应考虑行积极的外科手术.椎间盘切除和椎体间融合术是目前治疗椎间盘源性下腰痛最普遍和最有效的方法.     

椎间盘源性下腰痛与椎间盘内神经生长

疼痛的椎间盘外层纤维环、内层纤维环和髓核中都有神经纤维分布。体外研究发现椎间盘基质成分中蛋白多糖含量和结构变化,尤其是硫酸软骨素含量变化对神经生长具有明显的调节作用。在退变的椎间盘中,硫酸软骨素含量减少有利于椎间盘外周分布的神经纤维向内层纤维环甚至髓核内生长,从而导致椎间盘源性下腰痛。     

结缔组织生长因子在椎间盘纤维化和退变中的表达和作用

目的研究疼痛椎间盘组织中结缔组织生长因子（connective tissue growth factor, CTGF）的表达及其在椎间盘纤维化和退变中的作用。方法收集腰椎后路融合过程中切除的43个疼痛的病理椎间盘，来自于28例行腰椎后路椎体间融合手术的严重椎间盘源性下腰痛患者；同时收集16个在MRIT2加权像信号强度明显减弱的无腰痛症状的退变椎间盘，取自于6例腰椎管狭窄症和8例多节段腰椎后路融合的患者（年龄44～75岁，平均53．5岁，男女比例为8：6）和8个正常对照椎间盘，来自于4具新鲜尸体标本（22～39岁，平均28岁）的L。和蛉．椎间盘。均行组织学检查并用免疫组化方法检测CTGF在不同椎间盘组织的表达。结果组织学检查发现，疼痛椎间盘组织显示不同程度的慢性血管化炎症反应。纤维环组织失去正常的胶原纤维板层结构，板层结构断裂、紊乱或相互交叉融合，正常的成纤维细胞被软骨细胞替代。髓核显示明显纤维化、血管浸润或形成炎性肉芽组织，软骨细胞被成纤维细胞所替代。免疫组化染色显示CTGF在疼痛椎间盘大量表达，无腰痛症状的退变椎间盘有少量表达，正常对照椎间盘没有表达。结论疼痛的退变椎间盘在组织学上明显不同于无腰痛症状的退变椎间盘。CTGF在疼痛椎间盘的大量表达可能与椎间盘纤维化和退变过程密切相关。     

腰椎间盘造影术

虽然椎间盘造影术在诊断方面仍有争议,它仍是目前诊断椎间盘源性下腰痛的最重要手段,它能明确决定哪一个椎间盘是疼痛的椎间盘,它是目前对椎间盘源性下腰痛病人行腰椎融合手术前的必须检查。50以上人群中椎间盘退变是普遍的,MRI不能区分在T2加权上信号减弱的腰椎间盘是正常老化的椎间盘还是疼痛的病理椎间盘。诱发的腰椎间盘造影术能够呈现疼痛反应与椎间盘异常形态学的相关性。椎间盘造影后的CT扫描能够准确地研究纤维环撕裂解剖学。     

山羊腰椎间盘损伤后蛋白基因产物9．5免疫组化染色阳性神经纤维的分布

目的：观察山羊腰椎间盘损伤后不同时间点蛋白基因产物9．5（protein gene product 9．5，PGP9．5）免疫组化染色阳性神经纤维在损伤椎间盘内的分布，探讨山羊椎间盘损伤后是否出现神经内生长。方法：15只6月龄山羊，用直径1．2mm的穿刺针刀刺伤L5/6椎间盘前纤维环全层和L6／7椎间盘后部纤维环内层，L4/5椎间盘作为对照椎间盘。在造模后3周、3个月、6个月各取5只动物处死，取目标椎间盘光镜下观察椎间盘后部纤维环的组织学改变，检测PGP9．5免疫阳性神经纤维的分布并用半定量方法进行评分。结果：在观察期间L6／7椎间盘后部损伤纤维环未愈合，L4/5椎间盘在各个时间点均未出现裂隙，L5/6椎间盘仅在6个月时有1个椎间盘出现多个裂隙。损伤后3、6个月，在L6/7椎间盘右后1／4区很容易检测到PGP9．5免疫阳性神经纤维，神经纤维沿穿刺道及周围组织向内生长。L4／5和L5/6椎间盘相同区域未检测到相关免疫阳性反应神经纤维。在髓核中没发现PGP9．5免疫染色阳性神经纤维。结论：山羊经椎间盘前方损伤后部纤维环内层后，纤维环内层很难愈合，并出现PGP9．5免疫阳性神经纤维分布，说明椎间盘后部纤维环内层损伤可发生神经内生长。     

椎间盘内电热疗法的临床应用及研究进展

椎间盘内电热疗法(IDET),是近年来出现的一种治疗椎间盘源性疼痛(discogenic pain)的微创技术.通过封闭纤维环内小裂隙、加固椎间盘结构、加热灭活椎间盘内炎症因子和降解酶及使分布在纤维环外层的痛觉神经末梢灭活,起到治疗作用.IDET的特点是温度可控性好,对周围正常组织伤害较小等.IDET作为一种新兴的技术,治疗椎间盘源性腰痛微创、有效、安全.     

TNF-α和PGP9.5在椎间盘源性腰痛患者椎间盘MRI高信号区中的表达

目的:探讨肿瘤坏死因子-α(TNF-α)和蛋白基因产物9.5(PGP9.5)与腰椎间盘MRI高信号的关系.方法:26例经椎间盘造影诊断的椎间盘源性腰痛患者,男16例,女10例,年龄26～65岁,疼痛源性椎间盘MRIT2像均可见高信号区(HIZ区),均行手术治疗,取手术切除的椎间盘组织行TNF-α和PGP9.5免疫组化染色观察.并与4例脊柱侧凸患者矫形手术时取出的椎间盘组织进行对比.结果:椎间盘源腰痛患者椎间盘HIZ区对应部位的椎间盘组织表现为血管化肉芽组织和不同退变程度的髓核,可见大量增生的软骨样细胞和血管内皮细胞,免疫组化染色均可观察到TNF-α免疫染色阳性细胞和PGP9.5免疫阳性细胞:对照组没有观察到TNF-α免疫染色阳性细胞和PGP9.5免疫染色阳性细胞.H亿区TNF-α免疫阳性细胞明显多于HIZ区周边纤维环组织和对照组(P＜0.05),PGP9.5免疫阳性细胞亦明显多于HIZ区周边纤维环组织和对照组(P＜0.05).结论:椎间盘源性腰痛患者腰椎间盘MRI的HIZ区中有大量TNF-α免疫阳性细胞和PGP9.5免疫阳性细胞表达,其可能是HIZ作为致痛源性椎间盘特异性影像标志物的基础.     

The pathogenesis of discogenic low back pain

Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament (NF200) and neuropeptides such as substance P (SP) and vasoactive-intestinal peptide (VIP) in the nerve fibres. The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. SP-, NF- and VIP-immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain.     

Pathophysiology,diagnosis, and treatment of discogenic low back pain

Discogenic low back pain is a serious medical and social problem, and accounts for 26%-42% of the patients with chronic low back pain. Recent studies found that the pathologic features of discs obtained from the patients with discogenic low back pain were the formation of the zones of vascularized granulation tissue, with extensive innervation in fissures extending from the outer part of the annulus into the nucleus pulposus. Studies suggested that the degeneration of the painful disc might originate from the injury and subsequent repair of annulus fibrosus. Growth factors such as basic fibroblast growth factor, transforming growth factor β1, and connective tissue growth factor, macrophages and mast cells might play a key role in the repair of the injured annulus fibrosus and subsequent disc degeneration. Although there exist controversies about the role of discography as a diagnostic test, provocation discography still is the only available means by which to identify a painful disc. A recent study has classified discogenic low back pain into two types that were annular disruption-induced low back pain and internal endplate disruption-induced low back pain, which have been fully supported by clinical and theoretical bases. Current treatment options for discogenic back pain range from medicinal anti-inflammation strategy to invasive procedures including spine fusion and recently spinal arthroplasty. However, these treatments are limited to relieving symptoms, with no attempt to restore the disc’s structure. Recently, there has been a growing interest in developing strategies that aim to repair or regenerate the degenerated disc biologically.     

The pathogenesis and clinical significance of a high-intensity zone (HIZ) of lumbar intervertebral disc on MR imaging in the patient with discogenic low back pain

Recently, the presence of a high-intensity zone (HIZ) within the posterior annulus seen on T2-weighted MRI has aroused great interest and even controversy among many investigators, particularly on whether the HIZ was closely associated with a concordant pain response on awake discography. The study attempted to interpret the correlation between the presence of the HIZ on MRI and awake discography, as well as its characteristic pathology. Fifty two patients with low back pain without disc herniation underwent MRI and discography successively. Each disc with HIZ was correlated for an association between the presence of a HIZ and the grading of annular disruption and a concordant pain response. Eleven specimens of lumbar intervertebral discs which contain HIZ in the posterior annulus from 11 patients with discogenic low back pain were harvested for histologic examination to interpret the histologic basis of a nociceptive response during posterior lumbar interbody fusion (PLIF). The study found that in all of 142 discograms in 52 patients, 17 presented HIZ. All 17 discs with HIZ showed painful reproduction and abnormal morphology with annular tears extending either well into or through the outer third of the annulus fibrosus. The consecutive sagittal slices through the HIZ lesion showed that a notable histologic feature of the formation of vascularized granulation tissue in the outer region of the annulus fibrosus. The current study suggests that the HIZ of the lumbar disc on MRI in the patient with low back pain could be considered as a reliable marker of painful outer anular disruption.     

腰椎间盘MRI高信号区在诊断椎间盘源性下腰痛中的意义

目的:探讨腰椎间盘MRI高信号区(HIZ)在诊断椎间盘源性下腰痛中的作用。方法:对52例经保守治疗无效、CT影像上无腰椎间盘突出的下腰痛患者行腰椎MRI检查和腰椎间盘造影术,分析腰椎间盘MRI高信号区与腰椎间盘造影诱发的下腰痛之间的关系。结果:在行腰椎间盘造影的142个椎间盘中,共有38个椎间盘呈现疼痛复制反应,其中17个椎间盘显示高信号区。这17个有高信号区的椎间盘在椎间盘造影过程中全部呈现2～3级的纤维环破裂和疼痛复制反应。结论:无椎间盘突出的下腰痛患者在腰椎MRI上存在椎间盘内高信号区,可表明该椎间盘是产生腰痛的破裂椎间盘。     

高强度聚焦超声对离体兔腰椎间盘的生物学效应

目的观察不同剂量高强度聚焦超声对兔离体腰椎间盘的生物学效应。方法取6例剥离软组织的兔腰骶段脊柱标本（L1～S1）。将频率为9.6MHz、脉冲1 000Hz、剂量5W、焦距4mm的高强度聚焦超声从正前方聚焦于6例脊柱的L1S1椎间盘,各持续3、6、9、12、15、18min。此过程中,用热电偶针监测前方纤维环处与髓核交界处、HIFU焦点处、后方纤维环与髓核交界处、椎管内脊髓前表面的温度。结果 HIFU辐照过程中,监测点的温度逐渐升高,但升高的速度逐渐下降。HIFU在椎间盘前、后方纤维环处都能提供50℃以上的高温,并持续6min以上;焦点处能提供80℃以上的高温,并持续6min以上。结论高强度聚焦超声在椎间盘纤维环内可以提供足够高的温度,灭活纤维环内神经感受器可使髓核溶解、变性、萎缩,是治疗椎间盘源性腰痛的潜在方法。     

Annular tears and disc degeneration in the lumbar spine. A post-mortem study of 135 discs.

We studied 135 lumbar discs from 27 spines removed post-mortem from subjects of an average age of 31.5 years. Defects of the annulus fibrosus were classified as peripheral, circumferential or radiating; the nucleus pulposus as normal, moderately or severely degenerate. Peripheral tears were more frequent in the anterior annulus, except in the L5-S1 disc. Circumferential tears were equally distributed between the anterior and the posterior annulus. Almost all the radiating tears were in the posterior annulus, and closely related to the presence of severe nuclear degeneration. Histology suggested that peripheral tears were due to trauma rather than biochemical degradation, and that they developed independently of nuclear degeneration. The association of peripheral annular lesions with low back pain is uncertain but our study suggests that they may have a role in the pathogenesis of discogenic pain.     

Intervertebral disc a source of pain? Low back pain: problems and future directions--case reports

OBJECTIVE: The objective of this article is to provide evidence supporting the idea that intervertebral disc is a source of low back pain. SUMMARY OF BACKGROUND DATA: Diagnostic tests currently available for diagnosis of a painful disc are inadequate. Treatment protocols for low back pain generally ignore the presence of a painful disc. Pathological processes that may be responsible for discogenic pain are incompletely understood. Without diagnosis and treatment, disc disruption evolves to advanced stages of spinal dysfunction. New treatment modalities are becoming available which if applied early may stop disc disruption. CASE REPORTS: We describe here two case reports where discogenic nature of patients' symptoms was suspected based on patients' history, MRI findings and discography. We highlight the inadequacies of spinal imaging and discography in detecting at painful disc. A treatment (Intradiscal electrothermal therapy) was then directed exclusively to the intervertebral discs. We provide arguments that link discal therapy to resolution of patients' symptoms. Resolution of patients' symptoms after the discal treatment raised our suspicion that pain emanated from the intervertebral discs. CONCLUSIONS: Intervertebral disc is a source of low back pain that is often ignored. No diagnostic test currently exists that can reliably confirm presence of a painful disc. Early diagnosis and treatment of a painful disc may reduce enormous pain and suffering from low back pain.     

MRI高信号区与椎间盘造影在椎间盘源性腰痛诊断中的相关性研究

目的 研究腰椎间盘MRI高信号区(HIZ)与椎间盘造影诱发疼痛反应之间的关系,为椎间盘源性下腰痛诊断和治疗提供参考.方法 对37例长期慢性下腰痛、无典型的神经根性症状和体征,且CT证实无椎间盘突出的患者行MRI检查和腰椎间盘造影.分析造影后的X线片和CT片,并结合造影时诱发的疼痛反应,比较其与腰椎间盘MRI高信号区之间的关系.结果 37例患者共行98个腰椎间盘造影,21个椎间盘疼痛反应阳性,其中有HIZ的间盘10个,占47.6%.77个疼痛反应阴性的椎间盘中,有HIZ的间盘29个,占37.6%.纤维环破裂程度分级越高,MRI出现高信号区的比例也越高,说明有高信号区的纤维环破裂程度高,无高信号区的纤维环破裂程度低(P＜0.01);而高信号区与造影疼痛反应阳性之间并无明显一致性(P＞0.05).结论 MRI高信号区在诊断椎间盘源性腰痛中仅为提示性和筛选性的影像学征象,不能替代椎间盘造影的金标准.