An observation of ruptured annulus fibrosus in lumbar discs.

To observe anatomical or pathological changes in lumbar intervertebral discs, discography and computed tomography-discography (CTD) were performed on fresh human cadavers. The results of discograms and CTD were compared with histological findings of cross sections of discs. Preoperative CTD of lumbar disc herniation was investigated based on these results. Ruptures of the annulus fibrosus were divided into two categories: circumferential rupture and radial rupture. In CTD images of fresh human cadavers, most images of rupture of the annulus fibrosus showed anterior to lateral circumferential rupture. As disc degeneration progressed, circumferential rupture tended to coexist with radial rupture in many cases. In CTD cases of lumbar disc herniation, most images of ruptures of the annulus fibrosus showed a posterior radial rupture, which was the route for herniated nucleus. The greater the degree of degeneration, the more the images tended to show radial ruptures coexisting with circumferential ruptures.     

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.     

Intradiscal solid phase displacement as a determinant of the centripetal fluid shift in the loaded intervertebral disc

STUDY DESIGN: The movement of cross sections of the monofilament nylon threads inserted into the axially loaded intervertebral disc was traced with magnetic resonance imaging (MRI). This technique allowed the observation of the sequential solid phase displacement of the loaded intervertebral disc. OBJECTIVES: To clarify sequential solid phase displacement of the axially loaded intervertebral disc to elucidate the cause of centripetal fluid shift within a disc. SUMMARY OF BACKGROUND DATA: We already have reported that there is a centripetal fluid shift within the axially loaded intervertebral disc during the early phase of loading. We assumed that there should be an elaborate intradiscal matrix displacement that generates a pressure gradient within the disc to cause a centripetal fluid shift. METHODS: Thirteen freshly obtained bovine caudal intervertebral discs were prepared. Three to five monofilament nylon threads were inserted into each disc in the anterior-posterior direction to trace the intradiscal solid phase displacement on the midcoronal MR images. Sequential displacement of the disc matrix was recorded during a 294 N axial loading. RESULTS: Relatively large centrifugal expansion at the inner layer of the anulus fibrosus compared with less centrifugal expansion of the outer anulus fibrosus was observed in accord with gradual creep of the disc thickness. CONCLUSIONS: The uneven displacement of the intradiscal solid phase observed in the present study expels the fluid phase from the inner anulus fibrosus, thus resulting in accumulation of fluid phase in the nucleus pulposus. The present study suggests the presence of a mechanism that retains water within the normal intervertebral disc, in spite of an external load, because it forms a water-abundant nucleus pulposus, which is surrounded by an anulus fibrosus with decreased water permeability caused by fluid loss. A more detailed analysis is required to clarify topographic volumetric changes within the disc.     

纤维环穿刺诱导椎间盘退变动物模型的实验研究

目的：探讨纤维环穿刺诱导椎间盘退变建立动物模型的可行性。方法：新西兰大白兔24只，用持针器夹持18G皮肤穿刺针从左前外侧刺人L3/4、L4/5、L5/6椎间盘的纤维环，深度控制在5mm。术前及术后3、6、10周对造模后的椎间盘及对照的椎间盘（L2／3）行MRI检查，并行免疫组化及组织学观察。结果：术后第3周到第10周，造模后的椎间盘MRI T2WI信号呈现持续减弱趋势，免疫组化及组织学观察发现髓核细胞的数量及Ⅱ型胶原含量较对照间盘进行性减少（P〈0．01）。结论：纤维环穿刺法可以诱导兔椎间盘的缓慢退变，为研究椎间盘的退行性变提供有效的动物模型。     

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.     

Human intervertebral disc internal strain in compression: The effect of disc region,loading position,and degeneration

The primary function of the disc is mechanical; therefore, degenerative changes in disc mechanics and the interactions between the annulus fibrosus (AF) and nucleus pulposus (NP) in nondegenerate and degenerate discs are important to functional evaluation. The disc experiences complex loading conditions, including mechanical interactions between the pressurized NP and the surrounding fiber‐reinforced AF. Our objective was to noninvasively evaluate the internal deformations of nondegenerate and degenerate human discs under axial compression with flexion, neutral, and extension positions using magnetic resonance imaging and image correlation. The side of applied bending (e.g., anterior AF in flexion) had higher tensile radial and compressive axial strains, and the opposite side of bending exhibited tensile axial strains even though the disc was loaded under axial compression. Degenerated discs exhibited higher compressive axial and tensile radial strains, which suggest that load distribution through the disc subcomponents are altered with degeneration, likely due to the depressurized NP placing more of the applied load directly on the AF. The posterior AF exhibited higher compressive axial and higher tensile radial strains than the other AF regions, and the strains were not correlated with degeneration, suggesting this region undergoes high strains throughout life, which may predispose it to failure and tears. In addition to understanding internal disc mechanics, this study provides important new data into the changes in internal strain with degeneration, data for validation of finite element models, and provides a technique and baseline data for evaluating surgical treatments. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 547–555, 2011     

Histological changes in aging lumbar intervertebral discs. Their role in protrusions and prolapses

To study the relationships between the changes due to aging in lumbar intervertebral discs and the development of protrusion or prolapse, we carried out histological studies on operative specimens of thirty-one discs, of which twenty-two had been protruded and nine, prolapsed. The specimens were obtained during twenty-nine operations for herniation of a lumbar intervertebral disc in patients who were sixty years old or older. Changes in the anulus fibrosus were more extensive in the nine prolapsed discs than in the twenty-two protruded discs. Of the nine prolapsed discs, myxomatous degeneration, fibrosis, and swollen anular fibers were found in all nine, and cysts were seen in five. Of the twenty-two protruded discs, only five showed myxomatous degeneration; ten, fibrosis; one, a cyst; and sixteen, swollen fibers. For comparison, we also studied specimens that had been obtained at operation from twenty-one other patients, twenty to fifty-nine years old, who had a prolapsed disc. The anulus showed myxomatous degeneration in all twenty-one specimens, cysts in eight, and fibrosis in ten. In addition, we examined 368 autopsy specimens from people who had been between twenty-five and eighty-five years old at the time of death. In many of the subjects who had died in the sixth decade of life or later, we found that the orientation of the inner fiber bundles of the anulus fibrosus was reversed, so that they bulged inward. The reversal appeared to be the result of myxomatous degeneration of the middle fibers of the anulus, atrophy of the nucleus, and narrowing of the disc space. These histological findings suggest explanations for the predominance of protrusions of the nucleus pulposus in patients who are less than sixty years old and of prolapse of the anulus fibrosus in the few patients who are more than sixty years old who have herniation of an intervertebral disc.     

Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs

While there is consensus in the literature that blood vessels are confined to the outer anulus fibrosus of normal adult intervertebral disc, debate continues whether there is a vascular in-growths into inner parts of the intervertebral disc during degeneration. We therefore tested the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. The specific endothelial cell marker CD 31 (PECAM) was used to immunohistochemically investigate 42 paraffin-embedded complete mid-sagittal human intervertebral disc sections of various ages (0–86 years) and varying extent of histomorphological degeneration. Additionally, 20 surgical disc samples from individuals (26–69 years) were included in this study. In discs of fetal to infantile age, blood vessels perforated the cartilaginous end plate and extended into the inner and outer anulus fibrosus, but not into the nucleus pulposus. In adolescents and adults, no blood vessels were seen except for the outer zone of the anulus fibrosus adjacent to the insertion to ligaments. The cartilaginous end plate remained free of vessels, except for areas with circumscribed destruction of the end plate. In advanced disc degeneration, no vessels were observed except for those few cases with complete, scar-like disc destruction. However, some rim lesions and occasionally major clefts were surrounded by a small network of capillary blood vessels extending into deeper zones of the anulus fibrosus. A subsequent morphometric analysis, revealed slightly “deeper” blood vessel extension in juvenile/adolescent discs when compared to young, mature and senile adult individuals with significantly “deeper” extension in the posterior than anterior anulus. The analysis of the surgical specimens showed that only sparse capillary blood vessels which did not extend into the nucleus pulposus even in major disc disruption. Our results show that vascular invasion deeper than the periphery was not observed during disc degeneration, which supports the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. This study was supported by a grant from the AO/ASIF Foundation Switzerland (00-B72) and a grant from the AO Spine (SRN 02/103).     

Localization of cathepsins D, K, and L in degenerated human intervertebral discs.

STUDY DESIGN: Localization of cathepsins D, K, and L in degenerated intervertebral discs was examined by immunohistochemistry. OBJECTIVES: To determine the involvement of cathepsins in the pathomechanism of intervertebral disc degeneration by monitoring the immunolocalization of cathepsins in degenerated intervertebral disc tissue. SUMMARY OF BACKGROUND DATA: Cathepsins D, K, and L are enzymes that contribute to the matrix destruction seen in the articular cartilage affected by osteoarthritis and rheumatoid arthritis. However, little is known about the contribution of these cathepsins to intervertebral disc degeneration. METHODS: Paraffin-embedded sections of degenerated intervertebral disc tissue collected at the time of surgery (13 discs from 12 patients) were immunohistochemically stained with antibodies for cathepsins D, K, and L. For further characterization of the stained cells, immunohistochemical detection of CD68 and TRAP staining were performed. RESULTS: Hematoxylin and eosin staining revealed obvious signs of degeneration in all sections. Cathepsins D and L were immunolocalized in disc fibrochondrocytes at various sites exhibiting degeneration. Cathepsins K were found in tartrate-resistant acid phosphatase-positive multinucleated cells, in particular near the cleft within the cartilaginous endplate. However, few cells were positive for these cathepsins in anulus fibrosus that maintained the lamellar structure of collagen fibers. CONCLUSIONS: Marked expression of cathepsins D and L was observed at the site of degeneration. Cathepsins D and K localized in tartrate-resistant acid phosphatase-positive multinucleated cells existed at the cleft between the cartilaginous endplate and vertebral body. The site-specific localization of these cathepsins suggests the association of these proteinases with endplate separation and disorganization of the anulus fibrosus in degenerative spinal disorders.     

Immunohistochemical detection of Schwann cells in innervated and vascularized human intervertebral discs.

STUDY DESIGN: The ingrowth of nerves, blood vessels, and Schwann cells into human intervertebral discs was examined using immunohistochemistry for cell-type-specific markers. OBJECTIVES: To determine whether Schwann cells may contribute to disc innervation, and to assess the relation between disc innervation and vascularization. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration was associated previously with ingrowth of blood vessels and nerves. Schwann cells are known to play an important role in regulating nerve growth and survival in other tissues, but they have not been examined in human pathologic intervertebral discs. METHODS: Serial sections of human intervertebral discs were immunostained for the neuronal markers (neurofilament 200, peripherin, protein gene product 9.5), for the Schwann cell marker (glial fibrillary acidic protein), and for the endothelial cell marker (CD34). RESULTS: Glial fibrillary acidic protein-immunopositive cells colocalized with nerves in degenerate discs, but were absent or rarely observed in nondegenerate, aneural discs. These also were seen in the disc matrix, independently of nerves. Much of the nerve and Schwann cell ingrowth was found in vascularized areas of disc tissue, where the lamellar structure of the anulus fibrosus was disrupted. Blood vessels were observed deeper into the discs than nerves or Schwann cells. CONCLUSIONS: The appearance of glial fibrillary acidic protein-immunopositive cells in diseased intervertebral discs was closely associated with nerve ingrowth. This novel finding suggests that Schwann cells have a role to play in regulating disc innervation and nerve function in the disc. Because blood vessels were observed furthermost into the disc, it is possible that degenerate disc vascularization occurs before innervation.     

Intervertebral disc magnetic resonance image: correlation with gross morphology and biochemical composition

The magnetic resonance image, gross morphology, and biochemical composition of the intervertebral disc nucleus pulposus (NP), anulus fibrosus (AF) and cartilaginous endplates (CEP) from two groups of three human lumbar spines were compared. Group I consisted of all healthy discs from young donors (Grade I) and group II was comprised of discs that had undergone degeneration and age-related changes (average Grade 4). The gross morphological changes in the individual disc tissues associated with ageing/degeneration were consistent with specific changes in the characteristics of the magnetic resonance image. In particular, the mid-nuclear band of decreased magnetic resonance signal intensity seen in Grade 4 discs was associated with the appearance of clefts and fissures as well as a region of mucinous infiltration. The results of the biochemical analysis suggest that the changes in signal intensity are not due merely to changes in water content, but are also associated with changes in proteoglycan content. The changes associated with ageing/degeneration in the magnetic resonance image of the disc were related to a decrease in the proteoglycan content of the AF and NP. The water content of the NP also decreased. There was no clear association between the biochemical composition of the CEP and the magnetic resonance image. These results demonstrate that magnetic resonance imaging is an effective technique for evaluating subtle morphological changes in the intervertebral disc tissues and may be a sensitive indicator of the proteoglycan content of the AF and NP.     

Neural elements in human cervical intervertebral discs.

This study attempted to characterize neural elements within the human cervical intervertebral disc. Cervical intervertebral discs were obtained from four adult human subjects at autopsy. Discs were stained in bulk with gold chloride, sectioned, and viewed with the light microscope. Nerve fibers appeared to enter the disc in the posterolateral direction and course both parallel and perpendicular to the bundles of the anulus fibrosus. Nerves were seen throughout the anulus but were most numerous in the middle third of the disc. Receptors resembling Pacinian corpuscles and Golgi tendon organs were seen in the posterolateral region of the upper third of the disc. These results provide further evidence that human cervical intervertebral discs are supplied with both nerve fibers and mechanoreceptors.     

Observations on fiber-forming collagens in the anulus fibrosus

STUDY DESIGN: The spatial distribution of fiber-forming collagens in the anulus fibrosus was investigated in the complete longitudinal and horizontal sections of human lumbar intervertebral discs of seven individuals. OBJECTIVES: To obtain a more detailed structural definition of the anulus fibrosus because structural alterations of its collagen fiber network have been implicated in discal degeneration and other spinal pathologies. SUMMARY OF BACKGROUND DATA: Prior biochemical or immunofluorescence studies permitted only limited conclusions concerning the spatial distribution of the fiber-forming collagens in relation to anatomic structures because they were based on intraoperative tissue specimens or performed on incomplete sections of human intervertebral discs. METHODS: Complete human intervertebral discs with their adjacent vertebral bodies were fixed, decalcified, and embedded in paraffin. The intervertebral disc and its adjacent structures were reviewed in their entirety on one histologic slide. Monoclonal antibodies against human Types I, II, and III collagen were used for immunohistochemistry. A comparative analysis based on both immunohistochemical and histologic evaluation was performed. RESULTS: Type I collagen was seen abundantly in the outer zone and outer lamellas of the inner zone of the anulus fibrosus. On longitudinal sections, the Type I collagen distribution took the shape of a wedge. On horizontal sections, the Type I collagen positive area took the shape of a ring that was wider anteriorly than posteriorly. This suggests that the three-dimensional shape of the Type I collagen-positive tissue in the anulus fibrosus can be described by a donut that is wider anteriorly than posteriorly. Type II collagen was present in the entire inner of the anulus fibrosus, but not in the outer zone. In addition, it was found in the cartilaginous endplates. Type III collagen showed some codistribution with Type II collagen, particularly in pericellular locations in areas of spondylosis, which was noted at the endplates, vertebral rim, and insertion sites of the anulus fibrosus. CONCLUSIONS: These observations on the location of Types I and II collagen provide a more detailed structural definition of the anulus fibrosus, which may assist in further investigation of discal herniation.     

Histology of intervertebral disc protrusion: an experimental study using an aged rat model

STUDY DESIGN: In vitro experimental intervertebral disc ruptures of aged rats were examined histologically. OBJECTIVES: To clarify the mechanism of intervertebral disc herniations by microscopic investigation of ruptured discs. SUMMARY OF BACKGROUND DATA: Clinically, disc herniations have been classified into two types: extrusion and protrusion. However, the pathogenesis of protrusion type herniations has not yet been demonstrated by any studies. To clarify this issue, it is essential to establish an appropriate model producing disc herniations, and to examine the sequential changes in the structure of herniated discs. METHODS: Lumbar discs of 2-year-old rats were examined histologically and compared with human lumbar discs. To examine structural changes in discs subjected to repetitive motion stress, 400 repetitions of a sequence of flexion (30 degrees ) and axial rotation (6 degrees ) were applied in vitro to the lumbar discs of the animals. RESULTS: The microstructure of normal lumbar discs in aged rats was similar in many ways to the human lumbar discs in a 20- to 40-year-old adult. Of 10 discs subjected to repetitive stress, 4 were ruptured at the junction between the posterior anulus fibrosus and the sacral cartilage endplate. One had an extruded nucleus pulposus, and three had a protruded anulus fibrosus, which displayed disorganized structure containing widened and flaccid lamellae. CONCLUSIONS: The results from this study indicate that disc protrusion can be caused by disorganization of the ruptured annular lamellae, not by focal compression of the nucleus pulposus.     

Magnetic resonance imaging measurement of relaxation and water diffusion in the human lumbar intervertebral disc under compression in vitro.

STUDY DESIGN: Twelve lumbar intervertebral disc specimens were imaged with magnetic resonance imaging to estimate relaxation constants, T1 and T2, and tissue water diffusion, before and after applying compression. OBJECTIVES: The objectives of the study were to measure T1, T2, and water diffusion for differences with loading state, region of the disc (anulus fibrosus or nucleus pulposus), and grade of degeneration. SUMMARY OF BACKGROUND DATA: Magnetic resonance imaging can be used qualitatively to estimate water content and degeneration of the intervertebral disc. Beyond structural information of images, the relaxation times T1 and T2 may contain information on the changes occurring with degeneration. A modified spin-echo sequence can be used to estimate tissue water diffusion in cartilage and disc specimens with the ability to measure anisotropy. METHODS: Specimens were imaged in a 1.5-Tesla clinical scanner. T1, T2, and water diffusion were estimated from midsagittal images. Magnetic resonance imaging parameters were calculated before and after axial loading. The measured T1, T2, and D (diffusion coefficient) were compared before and after compression, and for the diffusion data, also by direction to consider anisotropy. RESULTS: For the T1 data, a significant difference was found by region, nucleus > anulus, and loading state, loaded > unloaded. For the T2 values, there was a significant difference by region, nucleus > anulus, and Thompson grade. For diffusion, significant differences were found by region, nucleus > anulus, Thompson grade, direction of diffusion, and state of compression, loaded > unloaded. CONCLUSIONS: This study demonstrated that magnetic resonance imaging can be used to measure significant changes in T1, T2, or diffusion in intervertebral disc specimens by region, loading condition, or Thompson grade.     

退变颈椎间盘中IL-17表达与分布的研究

目的 观察退变颈椎间盘中自细胞介素-17(IL-17)的表达与分布,并探讨其与颈椎间盘退变发生发展的关系.方法 实时荧光相对定量PCR(RQ-PCR)检测30例退变颈椎间盘及10例正常对照椎间盘中IL-1β、IL-17、肿瘤坏死因子-α(TNF-α)和孤核受体(retinoid-related orphan re-ce...     

Viscoelastic properties of intervertebral disc cells. Identification of two biomechanically distinct cell populations

STUDY DESIGN: A combined experimental and theoretical biomechanical study to quantify the mechanical properties of living cells of the porcine intervertebral disc. OBJECTIVES: To quantify zonal variations in the mechanical properties and morphology of cells isolated from the intervertebral disc. SUMMARY OF BACKGROUND DATA: Cellular response to mechanical stimuli is influenced by the mechanical properties of cells and of the extracellular matrix. Significant zonal variations in intervertebral disc matrix properties have been reported. No information is currently available on the corresponding regional variations in the mechanical properties of intervertebral disc cells, despite evidence of significant differences in cellular phenotype and biologic response to loading. METHODS: The micropipette aspiration test was used in combination with a three-parameter viscoelastic solid model to measure the mechanical properties of cells isolated from the anulus fibrosus, transition zone, and nucleus pulposus. RESULTS: Intervertebral disc cells exhibited viscoelastic solid behaviors. Highly significant differences were observed in the morphology, cytoskeletal arrangement, and biomechanical properties of the nucleus pulposus cells as compared with anulus fibrosus or transition zone cells. Cells of the nucleus pulposus were approximately three times stiffer and significantly more viscous than cells of the anulus fibrosus or transition zone. CONCLUSIONS: The findings of this study provide new evidence for the existence of two biomechanically distinct cell populations in the intervertebral disc. These differences in mechanical behavior may be related to observed differences in the cytoskeletal architecture between these cells, and may further play an important role in the development, maintenance, and degeneration of the intervertebral disc.     

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.     

Quantifying the contributions of structure to annulus fibrosus mechanical function using a nonlinear, anisotropic, hyperelastic model.

The annulus fibrosus of the intervertebral disc is comprised of concentric lamella of oriented collagen fibers embedded in a hydrated proteoglycan matrix with smaller amounts of minor collagens, elastin, and small proteoglycans. Its structure and composition enable the disc to withstand complex loads and result in inhomogeneous, anisotropic, and nonlinear mechanical behaviors. The specific contributions of the annulus fibrosus constituent structures to mechanical function remain unclear. Therefore, the objective of this study was to use a structurally motivated, anisotropic, nonlinear strain energy model of annulus fibrosus to determine the relative contributions of its structural components to tissue mechanical behavior. A nonlinear, orthotropic hyperelastic model was developed for the annulus fibrosus. Terms to describe fibers, matrix, and interactions between annulus fibrosus structures (shear and normal to the fiber directions) were explicitly included. The contributions of these structures were analyzed by including or removing terms and determining the effect on the fit to multidimensional experimental data. Correlation between experimental and model-predicted stress, a Bland-Altman analysis of bias and standard deviation of residuals, and the contribution of structural terms to overall tissue stress were calculated. Both shear and normal interaction terms were necessary to accurately model multidimensional behavior. Inclusion of shear interactions more accurately described annulus fibrosus nonlinearity. Fiber stretch and shear interactions dominated contributions to circumferential direction stress, while normal and shear interactions dominated axial stress. The results suggest that interactions between fibers and matrix, perhaps facilitated by crosslinks, elastin, or minor collagens, augment traditional (i.e., fiber-uncrimping) models of nonlinearity.