In vitro measurement of pressure in intervertebral discs and annulus fibrosus with and without annular tears during discography

BACKGROUND CONTEXT: Discogram studies have shown that pain reproduction correlates with the extent of annular disruption. However, it has not been assessed if pressure changes in the annulus fibrosus vary incrementally with intradiscal pressure. PURPOSE: To determine the relationship between intradiscal pressure and outer annular pressure during discography in intervertebral discs with and without annular tears. STUDY DESIGN: Intradiscal and periannular pressures were measured simultaneously in vitro during intradiscal injection in porcine cadaver spines. METHODS: Twenty fresh porcine cadaver lumbar spines with intervening discs were tested. Intradiscal and periannular pressures were measured simultaneously using two pressure sensors during intradiscal contrast injection. The tip of a 25-gauge needle connected with a pressure manometer was placed in the center of the nucleus pulposus. A second pressure transducer was located at the outer third of the annulus fibrosus. Needle and transducer locations were confirmed by fluoroscopy. To compare the intact and torn annulus fibrosus, annular disruptions were created with a 20-gauge needle and confirmed by fluoroscopy. RESULTS: During intradiscal injections of discs with an intact annulus, annulus fibrosus pressure remained low and a sharp increase in intradiscal pressure was observed. Significantly higher pressures were noted in the outer annulus in discs with annular tears (p<.01). Mean pressures at the central nucleus pulposus, the outer third of intact annuli and torn annuli were 93.4+/-40.9 psi, 14.8+/-1.9 psi and 85.7+/-24.8 psi, respectively. CONCLUSIONS: Volumetric injection of intervertebral discs with a torn annulus fibrosis during discography may increase intra-annular pressure similar to the increase in pressure that may occur during spinal loading activities. This effect may not occur in discs with an intact annulus fibrosus.     

Disc deterioration in low-back syndromes. A prospective, multi-center CT/discography study

Disc deterioration and pain provocation in different low-back pain syndromes was studied using computed tomography (CT) discography. Data were prospectively collected for 300 patients (816 discs). Patients were classified by their pre-discography diagnosis of disc herniation (DH), degenerated disc (DD), lumbar syndrome (LS), lumbar radicular syndrome (LRS), or other. The CT/discograms were classified by discographic pain response, the amount of degeneration and annular disruption. Eighty-two percent of DH patients, 80% of DD, 56% of LS, and 59% of LRS patients had both positive discographic pain provocation and moderate or severe disc deterioration. The study indicates that intradiscal pathology plays a major role in nonspecific low-back pain syndromes.     

The relationship of pain provocation to lumbar disc deterioration as seen by CT/discography

The CT/discographic findings from 225 discs in 91 low-back pain patients were compared to the pain provocation during the injection of contrast into the disc. The radiographic appearance of disc deterioration demonstrating disc degeneration and annular disruption of each disc was classified separately using a fourpoint scale: normal, slight, moderate, or severe. Pain reaction to the discogram at each level was recorded as follows: no pain, dissimilar pain, similar pain, or exact reproduction of the patient's clinical pain. This more precise analysis demonstrated a significant relationship between pain and deterioration of discs. The CT/discogram presents an axial view of the disc that allows a subgrouping of disc deterioration that can discriminate between peripheral deterioration (degeneration) and internal deterioration (disruption). The disruption supposedly occurs earlier and is more likely to be the source of exact pain reproduction.     

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。     

Biomechanical changes of the lumbar intervertebral disc after automated and nonautomated percutaneous discectomy: an in vitro investigation

Summary A total of 40 human lumbar motion segments were prepared and tested in an electromechanical materials testing machine to investigate the biomechanical changes, i.e., intradiscal pressure, radial extension, and height of the intervertebral disc, after percutaneous discectomy. In 20 discs (group A) the nuclear material was excised using the nonautomated percutaneous lumbar discectomy technique (NAPLD). In the other 20 (group B) the material was removed with the automated percutaneous lumbar discectomy method (APLD). The results of the two groups were analyzed statistically and compared to each other. In the NAPLD group the removal of 0.1 g freeze-dried nucleus pulposus material reduced the height of the disc an average of 0.32 mm, versus 0.47 mm in the APLD group. The radial bulge increased in both groups after the removal of 0.1 g freeze-dried nucleus pulposus material, on average 0.10 mm versus 0.15 mm. The intradiscal pressure also decreased in both groups after the removal of 0.1 g freeze-dried nucleus pulposus material, on average 0.94 bar versus 1.88 bar. The differences between the biomechanical data of the two groups were statistically significant for all three parameters (P<0.05). Our results show that the mechanism for improving radicular pain in patients with herniated disc after treatment with percutaneous discectomy is still in question. We postulate that loss of height of the disc and, as a consequence, reduction of tension in the affected nerve root, plays a major role with regard to this improvement.     

2000 Volvo Award winner in basic science studies: Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats

STUDY DESIGN: This study tested the hypothesis that the 17-kDa form of tumor necrosis factor-alpha is the pathophysiologic agent expressed by herniated nucleus pulposus in vivo that is primarily responsible for the histologic and behavioral manifestations of experimental sciatica associated with herniated lumbar discs. OBJECTIVE: The authors determined the molecular weight and concentration of active tumor necrosis factor-alpha in rat herniated disc and used exogenous tumor necrosis factor-alpha at the same molecular weight to study its neuropathologic effect on rat nerve root and dorsal root ganglion preparations in vivo. SUMMARY OF BACKGROUND DATA: Expressed by herniated nucleus pulposus in culture, tumor necrosis factor-alpha causes neuropathologic injury in nerve roots and neuropathic pain states in which mechanical allodynia is seen in response to peripheral stimuli. METHODS: Western blotting was used to identify the molecular weight of the operative tumor necrosis factor-alpha protein form, and measures of optical density were used for semiquantitative determination of concentration. Plastic-embedded nerve roots and dorsal root ganglion were used for neuropathologic evaluation, and von Frey stimulation was used to quantify mechanical allodynia. RESULTS: The 17-kDa form of tumor necrosis factor-alpha is expressed by herniated nucleus pulposus at a concentration of approximately 0.48 ng per herniated rat lumbar disc. Exogenous tumor necrosis factor-alpha applied in vivo to rat nerve roots produced neuropathologic changes and behavior deficits that mimicked experimental studies with herniated nucleus pulposus applied to nerve roots. CONCLUSIONS: The data reinforce other evidence that tumor necrosis factor-alpha is involved in mechanisms of neuropathic pain.     

Percutaneous laser disc decompression. A new therapeutic modality.

The authors present a new advance in the treatment of herniated disc disease using percutaneous Nd:YAG laser to vaporize a small portion of nucleus pulposus, thereby decompressing the disc. In vitro and in vivo animal data are presented. Three hundred seventy-seven magnetic resonance imaging or computed tomography scan-documented, herniated, nonsequestered lumbar intervertebral discs with corresponding clinical findings in 333 patients were so treated in an outpatient setting. The longest follow-up was 62 months, with a mean of 26 months. According to the Macnab criteria, there was a good to fair response in 261 patients (78.4%), and a poor response in 72 (21.6%); 166 patients experienced relief of pain during the procedure. One-third of repeat magnetic resonance imaging scans at 4-6 months postlaser treatment showed modest to moderate decrease of disc herniation.     

Discography and discogenic pain

Disc abnormalities, either directly or indirectly, are responsible for almost half the cases of back pain. A degenerated intervertebral disc without any impingement on adjacent nerve roots was suspected as a source of low-back pain in the 1920s. Discography is now considered a diagnostic procedure designed to determine whether a disc is intrinsically painful. The procedure involves inserting a needle into the nucleus pulposus and distending the disc with an injection of saline or contrast media. Postprocedure computed tomography can be used to highlight the features of internal disc disruption, which is the most commonly known cause of discogenic pain. The clinical history usually includes a deep, dull ache in the low back at the midline, with minimal radiation beyond the gluteal area and rarely to the knees and legs, no particular alleviating position, and pain that may worsen with axial loading. There is no accompanying sensory or motor loss. Provocative discography is widely used to identify the symptomatic intervertebral discs. Internal intervertebral disc derangement and positive provocation discography could be treated with surgical fusion or intradiscal electrothermal therapy. Application of heat to the intervertebral disc structure leads to thermal ablation of the nociceptors. Heat leads to contraction and shrinkage of collagen of the intervertebral disc and a decrease of the volume of the nucleus pulposus, resulting in a debulking of the intervertebral disc. Although intradiscal electrothermal therapy is a very promising procedure to treat discogenic pain, studies on its long-term effects, outcome measures, and cost-effectiveness are needed to validate the efficacy of this technique. Copyright © 2000 by W.B. Saunders Company     

Clinical evaluation of lumbar CT assisted discography in comparison with human cadaver

In order to estimate the clinical value of lumbar CT assisted discography (CTD), results obtained by this method were compared with histological findings of the cross section of the spine in fresh human cadavera. Based on these findings, preoperative CTD of lumbar disc herniation was investigated. In the discs of human cadavera, the contrast medium mainly invaded the fissures of nucleus pulposus and the ruptures of annulus fibrosus and then diffused to the surrounding tissues. These ruptures were classified into two categories: radial and circumferential. This identification was possible only in CTD and was obscure in the usual discogram. Not all the ruptures could be dyed in a severe degenerative disc, and a rupture which was not communicated with nucleus pulposus was not dyed in a mild degenerative disc. In the preoperative CTD of lumbar disc herniation, the posterior radial ruptures representing the route of herniated nuclei were characteristic and the circumferential ruptures were found complicated.     

Nerve root compression by herniated intradiscal gas. Case report

Intervertebral disc degeneration of any etiology may be associated with the formation of spaces or clefts within the disc. Gas collects within these spaces and can be seen roentgenographically. A case is presented in which intradiscal gas herniated into a connective tissue capsule, displacing the left S-1 nerve root and producing symptoms and signs identical to those of a herniated nucleus pulposus. The pathophysiology of gas within a disc space and the possibility that it may herniate much like the nucleus pulposus is discussed.     

诱发疼痛与椎间盘的病理变化：腰腿痛的CT椎间盘造影

作者对７３例腰腿痛患者进行了ＣＴＭ间盘造影检查，共１４６个间盘，其中突出５１个，退变９５个。根据造影中出现诱发疼痛与否，可分为无痛、非类似疼痛、类似疼痛和疼痛再现４类。椎间盘突出中６８． ９％有类似疼痛和疼痛再现。突出不合并或合并轻度退变时容易出现疼痛再现，合并严重退变则疼痛再现明显减少。无退变间盘常常是无痛的，退变间盘常有非类似疼痛。椎间盘造影诱发出的不同性质的疼痛有辅助诊断价值。疼痛的病理机制仍有待探讨。     

Immunophenotypic analysis of the inflammatory infiltrates in herniated intervertebral discs

STUDY DESIGN: The herniated portion of the lumbar disc was analyzed immunohistochemically for inflammatory infiltrates to determine their immunophenotype. OBJECTIVE: To investigate the pathomechanism behind spontaneous regression of herniated discs. SUMMARY OF BACKGROUND DATA: Spontaneous regression of herniated intervertebral discs has been increasingly reported. The inflammatory response of the host has been suggested as a factor in this phenomenon. However, whether the inflammation is induced from direct chemical irritation of the nucleus pulposus material or whether it is secondary to an autoimmune response to the nucleus pulposus remains controversial. METHODS: The herniated portion of the disc was collected from 38 patients who underwent surgery for lumbar disc herniation. Thin cryostat sections were made, and the extent to which inflammatory cells had infiltrated the disc specimen was defined. Then the immunophenotype of cellular infiltrates in the herniated disc specimens was assessed by immunostaining using a series of antibodies for lymphocyte, monocyte, macrophage, and dendritic cell markers. RESULTS: The inflammatory infiltrates in 14 of the 38 herniated discs were subjected to immunohistochemical analysis. None of them expressed the immunophenotypic markers of the lymphocyte (CD20, CD45RO, CD4, CD8, TCRgammadelta), mature monocyte (CD33), or dendritic cell (CD1a, CD80, CD86, S100). Abundant infiltration of CD68-positive cells that lacked CD33 but had a variable amount of CD11b, CD11c, and CD40 likely represents a process of differentiation from monocytes to macrophages. CONCLUSIONS: These findings are consistent with an immunophenotype of inflammatory responses to tissue injury or chemical irritation rather than antigen-specific immune responses. Therefore, understanding the mechanism of tissue repair is fundamentally important in the management of patients with disc herniations.     

磷脂酶A2在腰椎间盘突出症髓核中的表达及相关临床研究

目的：探讨磷脂酶A2（PLA2）在腰椎间盘突出症中的作用机制。方法：1．在术前和术中收集35例因腰椎间盘突出而手术的病人的疼痛程度、直腿抬高试验度数、突出病理征象等临床资料，采集突出组和对照组（8例）的血清和髓核标本。2、应用微孔比色法测定PLA2的活性。3．将获得的数据和临床资料进行统计学分析。结果：突出组髓核中的PLA2活性高于对照组，血清中两组无差异。髓核PLA2活性在破裂型或游离型中同在凸起型中的表达有差异（P＜0．05），与直腿抬高试验度数呈负相关（r=-0.344)，与疼痛存在相关性（P＜0．05）。结论：腰椎间盘出症髓核的PLA2活性高于正常腰椎间盘，化学性炎症机制在腰椎间盘突出症根性疼痛中发挥着可能比机械压迫更重要、更直接的作用，PLA2抑制剂有望成为治疗腰椎间盘突出症新一类药物。     

Neovascularization of the outermost area of herniated lumbar intervertebral discs

In 64 surgically treated herniated lumbar intervertebral discs, we performed histopathological studies of neovascularization in the outermost layer of the herniated mass in various types of hernia. We obtained specimens separately from the capsule tissue covering the herniated mass and the inner tip tissue of the herniated mass for comparison. Histologically, in most cases, the capsule tissue was the outermost layer of the annulus fibrosus or posterior longitudinal ligament, and the inner tip tissue was the nucleus pulposus. In the capsule tissue, newly formed small blood vessels were present in 73.4% of the total cases examined, regardless of the hernia type. However, the frequency and degree of such vessels in the tip tissue were significantly higher in hernias that perforated the posterior longitudinal ligament than in those that did not. When the intervertebral disc herniates, new blood vessels proliferate in the capsule of the hernial tissue. At the stage when the hernial capsule tissue is still present, these vessels were observed to have difficulty reaching the inner tip portion. These findings suggest that when the nucleus pulposus portion of the herniated mass perforates the posterior longitudinal ligament, it may be subject to a stronger neovascularization reaction. Received for publication on May 18, 1998; accepted on Jan. 19, 1999     

Clinical predictors of lumbar provocation discography: a study of clinical predictors of lumbar provocation discography

Discography is the only available method of directly challenging the discs for pain sensitivity. However, it is invasive, expensive and there is a debate about its clinical value. There is a need to identify clinical signs that may indicate the need for a discography examination. Pain centralization (retreat of referred pain to towards the spinal midline) has been associated with positive discography and possesses specificity between 80 and 100% depending on levels of disablement and psychosocial distress. Less than half of positive discography patients reports centralization and there is a need to identify other potentially valuable predictors. This study estimated the diagnostic accuracy of clinical variables in relation to provocation discography. In a blinded, prospective reference standard design in a private interventional radiology clinic, chronic low back patients received a detailed clinical examination followed by discography. Patients were typically disabled with high levels of psychosocial distress. Logistic regression modelling identified potentially useful clinical variables, and sensitivity, specificity and likelihood ratios were calculated for promising specific variables and combinations of variables. Of 118 consecutive discography cases, 107 had unconfounded data on discography results. History of persistent pain between acute episodes, a significant loss of extension and a subjective report of ‘vulnerability’ in what is termed as the ‘neutral zone’ had specificities of 83–92% and likelihood ratios between 2.0 and 4.1. Two combinations of variables were highly specific to positive discography, but no suitable screening test useful for ruling out positive discography was established. Three clinical variables have modest predictive power in relation to lumbar discography results and two combinations of variables were highly specific to positive discography.     

Metaplastic proliferative fibrocartilage as an alternative concept to herniated intervertebral disc

It is hypothesized on the basis of experimental intervertebral disc degeneration that herniated disc is actually newly synthesized proliferative metaplastic fibrocartilage and not herniation of pre-existing disc tissue, particularly that of the nucleus pulposus. Human material in selected surgical tissues was examined to test this concept. Histology revealed evidence for proliferative fronts of fibroblastic cells in herniated discs with hypocellular interiors. Hydroxypyridinium cross-link assay was used to determine the maturity of the collagen. Results indicated, with statistical significance, that herniated disc is a younger tissue than in situ annulus fibrosis, and that herniated disc is not from the nucleus pulposus, thus supporting the hypothesis.     

Experimental chemonucleolysis with recombinant human matrix metalloproteinase 7 in human herniated discs and dogs

Background contextChemonucleolysis has been proposed as a less invasive technique than surgery for patients with lumbar disc herniation. Once chymopapain had been approved as a chemonucleolysis drug, it was withdrawn because of serious complications. A novel agent with fewer complications would be desirable.PurposeThe purpose of this study was to investigate the effects of recombinant human matrix metalloproteinase 7 (rhMMP-7) in experimental chemonucleolysis in vitro and in vivo and examine its effects on tissue damage.Study designThe study design is the experimental study using human herniated discs and enzyme substrates in vitro and dogs in vivo.MethodsThe effects of rhMMP-7 on the degradation of human herniated discs were examined by measuring the wet weight in vitro. The correlations between the decrease in wet weight by rhMMP-7 and the conditions associated with herniated discs were also analyzed. The effects of rhMMP-7 on the proteoglycan and water contents were respectively examined with alcian blue staining and T₂-weighted magnetic resonance imaging at 7 days after intradiscal injection in dogs. The distribution of [¹²⁵I]-labeled rhMMP-7 was investigated by autoradioluminography at 7 days after intradiscal injection in dogs. An epidural injection study with rhMMP-7 was performed to evaluate the effects on the tissue damage around the discs at 1 and 13 weeks after the treatment in dogs. The Type 1 and 2 collagen cleavage rates were measured and compared with those of aggrecan in vitro.ResultsRecombinant human matrix metalloproteinase 7 concentration dependently decreased the wet weight of herniated discs in vitro. The decrease in wet weight of the discs by rhMMP-7 did not significantly correlate with the conditions associated with herniated discs. Intradiscal injection of rhMMP-7 reduced the proteoglycan and water contents, with an increase in the serum keratan sulfate levels. Radioactivity of [¹²⁵I]-labeled rhMMP-7 was detected in the nucleus pulposus and annulus fibrosus but not in the muscle. Epidural injection of rhMMP-7 had no effect on the injection site or the nerve tissues. The Type 1 and 2 collagen cleavage rates of rhMMP-7 were 1,000-fold weaker than those of aggrecan.ConclusionsThis study demonstrated experimental chemonucleolysis with rhMMP-7 in vitro and in vivo. The effects of rhMMP-7 were not affected by the conditions associated with herniated discs. The epidural injection study together with the autoradioluminography and in vitro enzyme assay suggests that intradiscal injection of rhMMP-7 may not induce tissue damage around the discs because of its distribution and substrate selectivity. Recombinant human matrix metalloproteinase 7 may be a novel and promising chemonucleolysis agent.     

Water, fixed charge density, protein contents, and lysine incorporation into protein in chymopapain-digested intervertebral disc of rabbit

Chymopapain (Discase) was injected at a dose of 0.125 nanokatal unit into the intervertebral discs of rabbits, and sequential changes in the metabolism of water, proteoglycan, collagen, and noncollagenous protein were investigated separately in the nucleus pulposus, anterior, and posterior anulus fibrosus. One week after chymopapain injection, the water and proteoglycan content was lower in all of the fractionated tissues of the anterior and posterior anulus and nucleus pulposus of the discs than in the control discs. In the anterior and posterior anulus, the proteoglycan content recovered after 12 weeks, but there was no recovery in the nucleus pulposus. The collagen content continued to increase up to the 12th week in the nucleus pulposus, while the noncollagenous protein content decreased in all tissue fractions after 1 week. In the anterior and posterior anulus, the content of noncollagenous protein recovered after 3 to 6 weeks, but there was no recovery in the nucleus pulposus. The lysine incorporation in collagen and noncollagenous protein was inhibited in all tissue fractions after 12 weeks, suggesting a decrease in synthetic activity. The intradiscal pressure calculated from proteoglycan hydration at 1 to 6 weeks after chymopapain injection showed a marked decrease to 0.8 to 0.9 atm, but it recovered to 1.6 atm after 12 weeks.     

腰部椎间盘造影及椎间盘内加压注射疗法

目的:探讨椎间盘内加压注射疗法对脱出型腰椎间盘突出症的治疗效果.方法:突出的椎间盘内加压注射3～20ml生理盐水,要避免用力过大,加压注射的压力低于3kg/cm^2.结果:脱出的椎间盘组织进入硬膜外腔后接触血液系统,逐渐被血液系统中的T细胞及单核细胞清除吸收.加压注射疗法能够促进这一吸收过程.结论:L1～5椎间盘和L5～S1椎间盘的穿刺体位和穿刺方向虽然有一定的差异,但是椎间盘内加压注射疗法是一种有效的治疗腰椎椎间盘突出症的微创疗法.     

Lumbar disc herniation. Computed tomography scan changes after conservative treatment of nerve root compression.

In 21 patients with computed tomography-diagnosed lumbar herniated nucleus pulposus, nerve root pain resolved after conservative treatment. A subsequent computed tomography scan was performed 6 months or more after presentation. This follow-up computed tomography scan was compared with the initial one. A definite decrease in size of the herniated nucleus pulposus was observed in 14 patients: disappearance in 5, obvious decrease in 5, and moderate decrease in 4. No definite change was observed in seven patients. Major computed tomography scan changes occurred significantly more frequently in large herniated nucleus pulposus than in small ones (p. less than 0.05). This study suggests that large lumbar herniated nucleus pulposus can decrease and even disappear in some patients treated successfully with conservative care.