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Purpose: Schmorl's nodes (SNs) are commonly seen in vertebral imaging of the normal adult population referred for different reasons and are duly noted by the radiologist. However, little is known about their etiology: either SNs are perceived as largely inert developmental or congenital herniations of disc tissue into weak areas of the vertebral end-plates, or they are perceived as a common pathological pathway of different adverse and general factors such as malignancy, trauma, infection, osteoporosis, Paget's disease and so forth. A commonly accepted morphological definition of what precisely constitute SNs does not exist, and consequently prevalences vary wildly in the literature. In the present study of 4,151 standardized lateral radiographs of the lumbar spine in an adult, Caucasian population between 22 and 93 years (median age 63 years, M 1,533, W 2,618)., Methods: We investigated prevalence, distribution and epidemiologic relationships of SNs., Results: SNs occur primarily in the upper part of the lumbar spine, and usually there are multiple lesions in the same individual. We could not establish any significant correlation between SNs and gender, age, BMI, height, weight or occupational exposure for heavy lifting. The overall prevalence was 3.8%. We did not find any significant correlations between SNs and overall degeneration of the lumbar spine., Conclusion: We found a prevalence of SNs in the lower end of the spectrum than hitherto reported.

Study Design: In vivo experimental study., Objective: The primary objective of the study was to investigate pressure transmission to adjacent discs during discography. A secondary objective was to quantify the transmitted pressure, both in contrast injected and noninjected porcine intervertebral discs., Summary of Background Data: Discography is used to before surgery identify painful discs. A pain response during discography that is concordant with the patient's experienced back pain is regarded as an indication that the injected disc is the source of pain. However, the sensitivity and specificity of discography are matters of debate. Pressure-controlled discographies have been reported to reduce the number of false-positive discs using low pressure criteria. Preliminary data indicated a transfer of pressure from an injected to an adjacent disc during discography. Pressure transmission in vivo during lumbar discography, not reported before might, if clinically present, contribute to a false-positive diagnosis., Methods: Thirty-six lumbar discs in 9 adolescent pigs were investigated. Intradiscal pressure was recorded during contrast injection, using a 0.36/0.25 mm fiber-optic pressure transducer inserted into the nucleus pulposus via a 22 G needle. The pressure was measured simultaneously in 2 adjacent discs during contrast injection into 1 of the discs at pressures up to 8 bar. Transmitted pressure was recorded both in noninjected discs and in discs that were prefilled with contrast., Results: Thirty-three discs were successfully examined. During contrast injection, there was an intradiscal pressure rise in the adjacent disc with a median value of 16.0% (range, 3.2-37.0) over baseline pressure. There was no significant difference in pressure increase between the noninjected and prefilled discs (P < 0.68)., Conclusion: Discography of porcine discs induces a pressure increase in adjacent discs. A similar pressure transfer during human clinical discography might elicit false-positive pain reactions.

The human spine is exposed to repeated loading during daily activities and more extremely during sports. Despite this, there remains a lack of knowledge regarding the immediate effects on the spine due to this mode of loading. Age-specific spinal injury patterns has been demonstrated and this implies differences in reaction to load mode and load history The purpose of the present study was to investigate the impact of cyclic pre-loading on the biomechanical properties and fracture patterns of the adolescent spine in an experimental model. Eight functional spinal units from four young porcine spines were harvested. The functional spinal units were cyclic loaded with 20,000 cycles and then axially compressed to failure. The compression load at failure, ultimate stress and viscoelastic parameters were calculated. The functional spinal units were examined with plain radiography, computer tomography and MRI before and after the loading, and finally macroscopically and histologically. The median compression load at failure in this study was 8.3 kN (range 5.6-8.7 kN). The median deformation for all cases was 2.24 mm (range 2.30-2.7 mm) and stiffness was 3.45 N/mm (range 3.5-4.5 N/mm). A fracture was seen on radiograph in one case, on CT and macroscopically in seven, and on MRI and histologically in all eight cases. The cyclic loaded functional spinal units in the present study were not more sensitive to axial compression than non-cyclic loaded functional spinal units from young porcine. The endplate and the growth zone were the weakest part in the cyclic loaded functional spinal units. Disc signal reduction and disc height reduction was found on MRI. The E-modulus value found in this study was of the same order of magnitude as found by others using a porcine animal model.

Morphological and behavioural changes in back muscles are common in back pain and injury. Recent data indicate a rapid reduction in the size of the multifidus, a deep back muscle, within 3 days of experimental intervertebral disc (IVD) injury in pigs. A reduced neural drive may contribute to this. We investigated changes in corticomotor excitability following IVD lesion by evaluation of the response of back muscles to electrical stimulation of the motor cortex. Motor evoked potentials (MEPs) were studied in 12 Swedish landrace pigs before injury, immediately after abdominal incision, immediately after L3-4 IVD lesion with a scalpel, and 15 min later. In two animals, responses were also evoked by descending volleys excited at the level of the mastoid processes (cervicomedullary evoked potentials) without motor cortex activation. In five animals, a sham procedure was followed without IVD lesion. MEPs were recorded in short (deep) and long (superficial) fibres of the multifidus at L3-5 on the lesioned side and at L4 contralaterally with intramuscular wire electrodes. Although the MEP amplitude increased in several muscles after incision, at 15 min after IVD lesion only the MEP amplitude of the deep L4 multifidus on the lesioned side was increased [36% (SD 15%), P < 0.05]. There were no changes in MEP amplitude after 15 min at adjacent or contralateral levels. The response to cervicomedullary stimulation reduced slightly. This suggests that the increased MEP amplitude was due to changes in cortical excitability. These data indicate that IVD lesion induces localized increases, and not decreases, in the excitability of cortical inputs to the deep paraspinal muscles that cross a lesioned disc.

Objective: This study was designed to clarify the role of the receptor activator of nuclear factor kappa B ligand (RANKL) in the process of discus degeneration and spondylarthrosis. It was hypothesized that experimental discus lesion would initiate not only local bone remodelling but also increased osteoclast formation on a location remote to the injury site due to altered spinal biomechanics. It was speculated that these changes in vertebral bone remodelling could be reflected in an increased RANKL expression., Methods: The presence of RANKL in the spine was studied in an experimental perforating lesion of the cranial endplate of L4 and the adjoining disc in six domestic pigs and in one human herniated disc. After three months, the experimental and contiguous control vertebrae, complete with intervertebral discs, were subjected for immunohistochemistry., Results: This is the first study to show that RANKL was locally seen (produced) in osteoblasts, fibroblasts replacing annulocytes and mesenchymal bone marrow cells and, in part, apparently bound to the surface of osteoclasts and macrophage-like prefusion macrophages. Such RANKL induction was also seen at sites remote from the experimental lesion driving the whole process. More RANKL-positive cells were found in close proximity to the endplate than in the central parts of the vertebrae. Osteocytes in bone matrix and most bone marrow cells in the marrow microenvironment showed no RANKL staining. Human annulus fibrosus also contained RANKL, RANK and OPG., Conclusions: We have demonstrated that RANKL is produced locally, also in soluble form, at the site of injury and also in intact vertebrae and bony structures likely due to altered biomechanics. It seems to be engaged in bone healing and remodelling, essentially proving our working hypothesis. These secondary bone changes could represent part of the degenerative spine disease (spondylarthrosis). RANKL inhibitors, like recombinant human osteoprotegerin (OPG), could be interesting drugs to test, not only in osteoporosis, but also in spondylarthrosis.

Study Design: Proteinases were immunohistochemically stained to analyze degenerated discs and paradiscal tissues in comparison to contiguous control tissues in an experimental porcine model of intervertebral disc degeneration., Objective: The aim was to analyze plasmin and metalloproteinases known to participate in mutual activation cascades., Summary of Background Data: Comparison of the degenerated discs and paradiscal structures with control tissues disclosed accumulation of plasmin and induction of matrix metalloproteinases (MMP), MMP-1 and MMP-2 in the discs, but some other MMPs in reactive and remodeling tissues., Material and Methods: In 6 domestic pigs, the cranial L4 endplate was perforated to penetrate the nucleus pulposus. Three months later, the animals were killed and the experimental and the contiguous control vertebrae, complete with their intervertebral discs, were excised and subjected to histologic and immunohistochemical examinations., Results: Immunohistochemical analysis disclosed increased expression of MMP-1 and MMP-2 in the traumatized and degenerated intervertebral discs. Some MMPs were also induced in all paradiscal structures (bone marrow, vertebral bone, and spinal ligaments), or decreased in already scarred areas. The common denominator for all the anatomic sites studied was accumulation of plasmin., Conclusion: Fibroblast collagenase (MMP-1) and gelatinase A (MMP-2), capable of degrading native and denatured collagen, were induced in degenerating intervertebral discs. Use of an experimental model enabled demonstration that biomechanical destabilization and degeneration of the disc also affects all other paradiscal structures, which are subjected to proteolysis and/or reparative fibrosis apparently representing remodeling of the spine subjected to pathologic stress. Profiling of various MMPs and plasmin, known to participate in mutual activation cascades, suggests that plasmin could activate pro-MMP-1, pro-MMP-2, pro-MMP-3, pro-MMP-7, pro-MMP-9, and pro-MMP-13 and alone or/and in cooperation with MMP-3 initiate at least 2 mutual MMPs activation cascades driven by activated MMP-3 and MMP-7.

Measuring intradiscal pressure is one way of mechanically assessing the discs degenerative state. In this study, the load-bearing capacity of degenerated and their adjacent lumbar intervertebral discs was evaluated using two different injury models. Seventeen adolescent pigs were divided into two groups, an annulus injury group and an endplate injury group. The annulus injury group was subjected to a stab incision in the L3-L4 disc, whereas the endplate injury group received a cranial endplate perforation of the L4 vertebral body. Both groups were biomechanically evaluated three months later using a miniaturized servohydraulic testing machine across L2-L4 and with two pressure needles inserted into the nucleus pulposus of the L2-L3 and L3-L4 discs. Linear relationships between the intradiscal pressure and the applied load were determined within the load range studied. When comparing the ratio of the injured to the adjacent disc pressure, the endplate injury was lower (mean value 0.31) than the annulus injury (mean value 0.51). The pressures in the discs adjacent to the degenerated level were found to be slightly higher. This increase can be expected due to a redistribution in mobility demands in segments adjacent to those with increased stiffness, i.e. degenerated intervertebral discs.

Study Design: Experimental study of muscle changes after lumbar spinal injury., Objectives: To investigate effects of intervertebral disc and nerve root lesions on cross-sectional area, histology and chemistry of porcine lumbar multifidus., Summary of Background Data: The multifidus cross-sectional area is reduced in acute and chronic low back pain. Although chronic changes are widespread, acute changes at 1 segment are identified within days of injury. It is uncertain whether changes precede or follow injury, or what is the mechanism., Methods: The multifidus cross-sectional area was measured in 21 pigs from L1 to S1 with ultrasound before and 3 or 6 days after lesions: incision into L3-L4 disc, medial branch transection of the L3 dorsal ramus, and a sham procedure. Samples from L3 to L5 were studied histologically and chemically., Results: The multifidus cross-sectional area was reduced at L4 ipsilateral to disc lesion but at L4-L6 after nerve lesion. There was no change after sham or on the opposite side. Water and lactate were reduced bilaterally after disc lesion and ipsilateral to nerve lesion. Histology revealed enlargement of adipocytes and clustering of myofibers at multiple levels after disc and nerve lesions., Conclusions: These data resolve the controversy that the multifidus cross-sectional area reduces rapidly after lumbar injury. Changes after disc lesion affect 1 level with a different distribution to denervation. Such changes may be due to disuse following reflex inhibitory mechanisms.

Background: Spinal loading during daily activity as it relates to the ability of the intervertebral disc to sustain its integrity has been a major issue in spinal research. The purpose of this investigation was to establish the relationship between the intervertebral disc pressure in the nucleus and the load applied to the motion segment in an in vivo porcine model., Methods: Nine domestic pigs were used in this study. A miniaturized servohydraulic testing machine was affixed to the lumbar spine via four intrapedicular screws, which were inserted bilaterally into the L2 and L3 vertebrae. A pressure needle was inserted through the lateral part of the L2-L3 disc annulus and into the nucleus pulposus. Force, deformation, and intradiscal pressure data were collected during a loading scheme that consisted of applying a set of constant loads in increasing order, that is, 50, 100, 150, 200, and 250 N. Each load was applied for 30 seconds followed by 30-second restitution., Results: Intradiscal nucleus pressure was found to correlate to the applied load in all cases. Linear regression analyses resulted in the following equation: intradiscal pressure (MPa) = 0.08 + 1.25E(-3)(load, N), r(2) = 0.81, n = 8. Intradiscal pressure was also highly linearly dependent on the stress. The intrinsic intradiscal pressure was found to be 81 +/- 5 kPa. The results also indicated that the pressure within the disc exhibited a creep behavior., Conclusion: In conclusion, pressure in the nucleus of the porcine intervertebral disc was linearly related to the applied load and stress.

The aim of this study was to create an experimental model of disc degeneration that closely mimicked human disc degeneration. In six domestic pigs, an L4 cranial endplate perforation into the nucleus pulposus was made. Three months postoperatively, compressive testing was performed on the L2-L4 motion segments, and intradiscal pressure was measured in the intervening discs. Histochemical and morphologic examinations were made on the excised degenerated and adjacent discs. A significant reduction in water content was observed in the outer anterior annulus of the degenerated disc. In the nucleus, the proteoglycan content was significantly reduced, as well as the cellularity, although not significantly. The nucleus lost its gel-like structure and was discolored, and there was delamination of annular layers. Intradiscal pressure in the nucleus was significantly lower in the degenerated disc. In conclusion, experimental degeneration of the intervertebral disc induced by endplate penetration resembled human disc degeneration, as exemplified by biochemical and structural changes.

The spinal viscoelastic structures including disk, capsule and ligaments were reviewed with special focus on their sensory motor functions. Afferent capable of monitoring proprioceptive and kinesthetic information are abundant in the disc, capsule and ligament. Electrical stimulation of the lumbar afferents in the discs, capsules and ligaments seem to elicit reflex contraction of the multifidus and also longissimus muscles. The muscular excitation is pronounced in the level of excitation and with weaker radiation 1 to 2 levels above and below. Similarly, mechanical stimulation of the spinal viscoelastic tissues excites the muscles with higher excitation intensity when more than one tissue (ligaments and discs for example) is stimulated. Overall, it seems that spinal structures are well suited to monitor sensory information as well as to control spinal muscles and probably also provide kinesthetic perception to the sensory cortex.

Study Design: The diagnostic performance of a newly described variable was assessed in an in vivo model of disc degeneration using a split-pair experimental design., Objective: To determine if vertebral displacement measures generated from ultrasonic indentation could distinguish between experimental and control groups of animals., Summary of Background Data: Few procedures are available that noninvasively assess subcutaneous vertebral mechanics. Information from such a procedure would be of value in determining potential clinical relevance of spinal mechanics with respect to low back pain., Methods: Eight adolescent pigs underwent endplate perforation surgery to initiate lumbar disc degeneration. After 4 months of recovery, these and eight age-matched controls were assessed by ultrasonic indentation, a noninvasive procedure that quantifies vertebral displacements in the plane of loading-indentation. Each animal then received a facetectomy and was reindented at the same location as confirmed by ultrasonic imaging. Discal materials were removed postmortem for analysis., Results: Degenerative discs exhibited morphologic changes consistent with early degenerative disc disease. Prefacetectomy comparison of vertebral displacement measures between control and experimental animals resulted in sensitivity, specificity, and diagnostic accuracy values of 75.0%, 83.3%, and 77%, respectively. After facetectomy these values increased to 87.5%, 83.3%, and 85%, respectively. These measures of diagnostic performance were comparable or superior to those of existing clinical techniques (invasive or otherwise) used to assess degenerative conditions of the spine., Conclusions: The results of this study suggest that noninvasive measures of vertebral displacement are clinically significant and possess the additional advantages of being objective and noninvasive.

Recent studies of the spine in adolescents who have sustained trauma have shown injuries to the growth zone, whereas injuries to the vertebral body have been described in other studies of only adults. There are also reports on different clinical signs and radiological findings in adolescents with lumbar disc herniation when compared to adults. In order to find an explanation for these differences between adolescents and adults, this experimental study was performed. Six cadaveric lumbar motion segments (vertebral body-disc-vertebral body) obtained from three young male pigs and six lumbar motion segments obtained from three mature male pigs were tested in axial compression to failure. All units were examined with plain radiography and magnetic resonance imaging before and after compression. After the compression, histological samples were taken from the injury site. In the adolescents, a fracture was consistently found in the endplate through the posterior part of the growth zone, displacing the anulus fibrosus with a bony fragment at the point of insertion to the vertebra. This type of injury could not be detected in any of the adults; instead, there was a fracture of the vertebra in four cases, and in two cases, a rupture of the anulus fibrosus without a bony fragment was seen. This study showed that, when compressed to failure, the weakest part of the lumbar spine of the adolescent pig differs from that of the mature pig in the same way that studies on human spinal units have shown.

Study Design: An experimental porcine study in which functional lumbar spinal units were tested in compression to failure. Biomechanical, radiographic, magnetic resonance imaging, and histological characteristics are described., Objectives: To explain the different patterns of injury seen in adults and adolescents resulting from traumatic injury to the vertebrae and to explain the mechanism behind traumatic displacement of the ring apophysis seen in athletes., Summary of Background Data: Recent investigations of the spine in adolescent who have sustained trauma have shown injuries to the growth zone, whereas studies of adults have shown injuries to the vertebral body. A higher frequency of abnormalities in the discs, the vertebral bodies, the endplates, and the ring apophyses has been demonstrated in athletes with high loads on the spine. There is controversy over the etiology of these changes., Methods: Twelve functional lumbar spinal units (vertebra-disc-vertebra) obtained from six young male pigs were tested in compression to failure. All units were examined with plain radiography and magnetic resonance imaging before and after compression. After the compression, histologic samples were taken from the injury site., Results: Identical traumatic changes were seen in all functional lumbar spinal units, i.e., fracture in the endplate through the growth zone posteriorly and displacement of the anulus fibrosus with a bony fragment at the point of insertion of the vertebra. The nucleus pulposus was ruptured and displaced through the fracture line in all cases. The injuries were not seen on radiographs but were detected on magnetic resonance images, as confirmed on microscopic and histologic examination., Conclusion: This study shows that the weakest part of the lumbar spine of the juvenile pig, when compressed, is the growth zone and the junction between the point of insertion of the anulus fibrosus and the vertebra. This location of weakness may explain the high frequency of disc degeneration and "persisting apophysis" seen in the spine of athletes.

The dynamic axial stiffness of the L2-3 motion segment subjected to vibratory loading under intact and injured states of the intervertebral disc was studied using an in vivo porcine model. Three groups of animals with the following states of the intervertebral discs were studied: intact disc, acutely injured disc, and degenerated disc. A miniaturized servo-hydraulic exciter was used to sinusoidally vibrate the motion segment from 0.05 to 25 Hz under a compressive load with a peak value of either 100 or 200 N. The dynamic axial stiffness of the intervertebral disc was calculated at 1-Hz intervals over the frequency range. The results showed that the dynamic axial stiffness was frequency dependent. A positive relationship was found between an increase in mean dynamic stiffness and load magnitude. An increase in mean stiffness with successive exposures at the same load magnitude was observed, despite the allowance of a recovery period between loading. The greatest difference was noted between the first and second load sets. No significant change in stiffness was found due to an acute disc injury, whereas a significant increase in mean stiffness was found for the degenerated disc group as compared with the intact group. The form of the frequency response curve, however, remained relatively unaltered regardless of the degenerated state of the disc. With heavier loads, repeated loading, and/or disc degeneration, the stiffness of the intervertebral disc increases. An increase in stiffness can mean a reduction in the amount of allowable motion within the motion segment or a potentially harmful increase in force to obtain the desired motion. This may locally result in greater stresses due to an altered ability of the disc to distribute loads.

Study Design: A porcine model was used to study whether muscular activation in the paraspinal muscles caused by nerve stimulation in the anulus fibrosus of a lumbar intervertebral disc could be altered by saline injection into the zygapophysial (facet) joint., Objectives: To elucidate possible mechanisms regarding the nerve pathways and interactions between the intervertebral disc, zygapophysial joints, and the paraspinal musculature., Summary of Background Data: The physiologic basis for chronic low back pain, including muscular spasm, is uncertain. Although extensive research involving the lumbar motion segments and the surrounding tissues has been performed, the neuromuscular connection has not been sufficiently investigated., Materials and Methods: Twenty-three adolescent pigs were used to measure the electromyographic response in the paraspinal musculature to electrical stimulation of the posterolateral L3-L4 anulus fibrosus, before and after introduction of physiologic saline into the zygapophysial joint. Motor unit action potentials were recorded using three sets of needle electrodes placed into the deepest fascicles of the multifidus, bilateral to the L4 and L5 spinous processes, and into the central longissimus musculature, bilateral to the L4 spinous process., Results: Stimulation of the nerves within the posterolateral anulus of the disc elicited reactions in the paraspinal muscles, namely the lumbar multifidus and longissimus. Introduction of physiologic saline into the zygapophysial joint resulted in a reduction in the motor unit action potential amplitude. This reduction was manifested as an immediate and constant reduction, a graded reduction, or a delayed reaction, during which the reduction occurred an average of 5 minutes after the saline injection., Conclusions: Introduction of physiologic saline into the zygapophysial joint reduced the stimulation pathway from the intervertebral disc to the paraspinal musculature. The zygapophysial joints may therefore have a regulating function, controlling the intricate neuromuscular balance in the lumbar motion segment.

The viscoelastic response of a lumbar motion segment loaded in cyclic compression was studied in an in vivo porcine model (N = 7). Using surgical techniques, a miniaturized servohydraulic exciter was attached to the L2-L3 motion segment via pedicle fixation. A dynamic loading scheme was implemented, which consisted of one hour of sinusoidal vibration at 5 Hz, 50 N peak load, followed by one hour of restitution at zero load and one hour of sinusoidal vibration at 5 Hz, 100 N peak load. The force and displacement responses of the motion segment were sampled at 25 Hz. The experimental data were used for evaluating the parameters of two viscoelastic models: a standard linear solid model (three-parameter) and a linear Burger's fluid model (four-parameter). In this study, the creep behaviour under sinusoidal vibration at 5 Hz closely resembled the creep behaviour under static loading observed in previous studies. Expanding the three-parameter solid model into a four-parameter fluid model made it possible to separate out a progressive linear displacement term. This deformation was not fully recovered during restitution and is therefore an indication of a specific effect caused by the cyclic loading. High variability was observed in the parameters determined from the 50 N experimental data, particularly for the elastic modulus E1. However, at the 100 N load level, significant differences between the models were found. Both models accurately predicted the creep response under the first 800 s of 100 N loading, as displayed by mean absolute errors for the calculated deformation data from the experimental data of 1.26 and 0.97 percent for the solid and fluid models respectively. The linear Burger's fluid model, however, yielded superior predictions particularly for the initial elastic response.

Study Design: In this study, a porcine model was used to study whether a nerve reaction in the anulus fibrosus of a lumbar disc or in a facet joint capsule could cause a muscular response in the multifidus musculature., Objectives: To determine if there is an interrelationship between the intervertebral disc and facet joint innervation and the multifidus musculature as a possible pain mechanism., Summary of Background Data: The innervation of the anulus fibrosus of the intervertebral disc and the capsule of the facet joint is well described in the literature, although the functions of these nerves are poorly understood. An interrelationship between this innervation and the paraspinal musculature has not been previously described., Methods: Fifteen adult pigs were used to measure the electromyographic response in the multifidus musculature to electrical stimulation of the lateral region of the disc anulus and the facet joint capsule in the L1-L2 motion segment. Motor unit action potentials were recorded using three sets of bipolar needle electrodes placed into the deepest fascicles of the multifidus, bilateral to the L2, L3, and L4 spinous processes. The effect of lidocaine injection into the facet joint and subperiosteal muscle detachment on the electromyographic response were studied., Results: Stimulation of the disc anulus fibrosus induced reactions in the multifidus on multiple levels and on the contralateral side, whereas stimulation of the facet joint capsule induced reactions predominantly on the same side and segmental level as the stimulation. Introduction of lidocaine into the facet joint resulted in a significantly reduced electromyographic response to either stimulation, with the most drastic reduction seen when stimulating the facet joint capsule. Subperiosteal detachment of the paraspinal muscles prevented any muscular response., Conclusions: Stimulation of the disc and the facet joint capsule produced contractions in multifidus fascicles. The clinical implications are that there may be interactive responses between injured or diseased structures, i.e., disc or facet joints, and the paraspinal musculature. Activation of the multifidus muscles may have a stabilizing effect, constraining the motion of the lumbar spine. Longstanding muscular contraction may produce ischemic conditions and may be a potential source of pain.

Study Design: Eighteen pigs were stabbed with a scalpel in the anterior part of the anulus fibrosus of a lumbar disc. After surgery, the pigs received either tiaprofenic acid or indomethacin daily, and a third group did not receive any medication., Objectives: Nonsteroidal anti-inflammatory agents are widely used in the treatment of low back patients, but their long-term effects on the matrix molecules in the degenerate disc are unknown., Summary of Background Data: Several in vitro and in vivo studies on articular cartilage have suggested that tiaprofenic acid may not have adverse effects on matrix metabolism, whereas indomethacin probably does., Methods: Uronic acid, DNA, and water contents were determined from five different locations in each injured disc. Transport and incorporation of sulfate were examined by in vivo radioactive tracer analysis, and proteoglycan structures were analyzed by gel electrophoresis., Results: Morphologically, there were no differences between the treatments. Tiaprofenic acid maintained a higher uronic acid content in the nucleus pulposus and outer anulus compared with that of the nonmedicated animals. Tiaprofenic acid decreased the incorporation of sulfate in the injured area and the water content at most sites. Indomethacin had no adverse effects compared with the nonmedicated group, and it increased water content in the posterior anulus fibrosus., Conclusions: Long-term administration of tiaprofenic acid and indomethacin did not have harmful effects on matrix metabolism after disc injury. On the contrary, tiaprofenic acid may slightly protect proteoglycans in the degenerating disc.

Study Design: The present study sought to elucidate the changes that occur in collagen chemistry in the early phases of disc degeneration., Objective: To monitor the healing process of the injured anulus fibrosus and the secondary degenerative reactions in the nucleus pulposus., Summary of Background Data: Despite the importance of collagen chemistry under pathologic conditions in the intervertebral disc, knowledge of this aspect is very limited., Methods: Fourteen pigs were stabbed with a scalpel blade in the anterior part of the anulus fibrosus of a lumbar disc. The animals were killed 2 weeks to 5 months after injury. The activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase, the total collagen content, and staining patterns for Types I, III, IV, and VI collagens were analyzed from different parts of the disc., Results: The most active phase of the healing process, assessed from the activities of enzymes involved in collagen biosynthesis, took place during the first month postoperatively. The anular lesion was found to cicatrize through formation of disorganized granulation tissue in which Type I, III, and, IV collagens were deposited. In the nucleus pulposus, activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase and total collagen content increased, and the originally rounded cells became more elongated, resembling fibroblasts., Conclusions: The results of this study suggest that the altered composition of collagens observed in the degenerate porcine nucleus pulposus results from changes in cell phenotype: Notochondral cells were replaced by fibroblast-like cells. It is likely that trauma to the anulus fibrosus can initiate a progressive degenerative process in the disc tissue.

An animal model of disk degeneration was used to study the concentration levels and types of proteoglycans in the different parts of the intervertebral disk. An annular incision was made with a scalpel blade into the anterior part of the porcine lumbar intervertebral disks via a retroperitoneal approach. Three months after injury the morphology of the injured disk had changed considerably. Disk height was diminished, and in the injured segment osteophytes had formed at the ventral edges of the vertebral body. The nucleus was small, fibrous, and yellowish. The annular lesion had healed by formation of granulation tissue, but the lamellar structure was partially destroyed. The concentration of inorganic [35S]sulfate had decreased across the whole disk, reflecting a decrease in the rate of solute transport. The concentration of incorporated [35S]sulfate had also decreased in the injured disks. The DNA concentration in the anterior annulus and in the nucleus had increased, whereas both the concentration of uronic acid and the ratio of chondroitin-6-sulfate to chondroitin-4-sulfate in the nucleus had decreased. Agarose gel electrophoresis combined with chondroitinase B digestion suggested the presence of dermatan sulfate proteoglycans in the injured annulus fibrosus. The morphology and chemical composition of the disks adjacent to the injured one were normal, and only a slight increase in the concentration of incorporated [35S]sulfate was observed in the disks above the injured one.

There is increasing evidence that-back pain may originate from degenerated or damaged disks, even in the absence of disk herniation. For a study of the pattern of innervation in injured disks, the anterior part of the annulus fibrosus of a lumbar disk in 11 domestic pigs was incised with a scalpel through a retroperitoneal approach. The animals were killed 2 weeks, 1, 2, 3, and 5 months postoperatively, and the whole anterior annulus of each injured disk and corresponding tissue from intact animals were excised. Cryostat sections 20 microns thick were cut from the surface downward, fixed, and stained with different antisera. Antisera to neurofilament triplet protein (R39), protein gene product (PGP) 9.5 and synaptophysin were used as general neural markers. Antiserum to substance P (SP) and calcitonin gene-related peptide (CGRP) were used to localize nerves mainly of the sensory type, and C flanking peptide of neuropeptide Y (CPON) to visualize nerve fibers of the sympathetic type. It was observed that in the intact porcine disk, the outer and middle parts of the anterior annulus were innervated to a depth of 7 mm from the annular surface, but the innermost annular layers showed no immunoreactivity to any of the neural antibodies. Disk injury did not cause any major changes in the nerve topography of the wound area, even though there were granulation tissue and neovascularization in this area.

Young domestic pigs were incised with a scalpel blade into the anterior part of annulus fibrosus of lumbar discs in order to study the reparative processes in the annulus fibrosus and the secondary reactions in the nucleus pulposus. Northern and slot-blot hybridizations were used to investigate type I, III, and VI collagen gene expression in the disc tissue. For this purpose a method for RNA isolation was modified so as to be applicable to the intervertebral disc, which has a low cell density and a high proteoglycan content in its extracellular matrix. The amount of total RNA was found to be very low, particularly in the nucleus pulposus. Intact RNA could be isolated from most parts of the injured discs, but only from the outer annulus of the control discs. Hybridizations showed that healing of the wound in the annulus fibrosus involves an increase in the synthesis of particularly type I and type III collagens. However, no changes in the collagen gene expression were detectable in the nucleus pulposus two weeks after the injury.

Spinal pain often is thought to be due to degeneration and mechanical failure of the intervertebral disc. Since the mechanical strength of the tissue depends on collagen fibers, the present study was designed to investigate the reactions in collagen metabolism after an experimentally induced disc injury. Five domestic pigs underwent an incision in the anterior part of the annulus fibrosus of disc L4-L5 through a retroperitoneal approach. The animals were killed 3 months postoperatively, and the injured discs and intact discs (controls) from different animals were removed for chemical analysis. Slices were cut from seven different parts across the disc. The concentration of total collagen (hydroxyproline [Hyp]), the activities of the two key enzymes in collagen biosynthesis (prolyl 4-hydroxylase [PH] and galactosylhydroxylysyl glucosyltransferase [GGT]), and the concentration of mature collagen crosslinks (hydroxypyridinium [HP]) were determined. In all experimental discs, the morphology had changed considerably: the nucleus pulposus was small, fibrous, and yellowish. The annular lamellar structure was partially destroyed and had been replaced by granulation tissue in the region of the injury. Large osteophytes had formed at the ventral edges of the vertebral bodies. In the nucleus pulposus, the Hyp concentration and the activities of PH and GGT were significantly increased, whereas the water content had decreased. The concentration of HP crosslinks was decreased in the anterior annulus fibrosus.

Oxygen concentration gradients in the intervertebral disc were calculated to examine the effects of exchange area and disc thickness on oxygen concentrations and oxygen flux into the disc. The concentration gradients were determined using the two-dimensional Poisson equation with experimental values for oxygen consumption rate and oxygen diffusion. The calculated gradients were steep, and the oxygen concentrations in the center of thick discs were low, in agreement with experimental gradients. The results support the hypothesis that maximum cell density in the disc is determined by nutrient supply and that exchange area and disc thickness are critical parameters.

There are strong indications that whole body vibrations are involved in the pathophysiology of different spinal aberrations known or assumed to generate back pain and sciatica. There also are several possible pathogeneses for these pathologic changes, although the proofs still are inconclusive or lacking. A better understanding of the relationships between vibration and spinal disorders in the near future will help us to prevent the occurrence of some of the problems causing pain and disability.

In vivo creep-recovery and disc pressure measurements were performed on the lumbar spine of immature and mature swine. The creep-recovery measurements were performed using a custom materials testing apparatus designed to apply static or dynamic loads to the spine of anesthetized animals. A series of three separate experiments were performed to assess the effects of: (I) animal death, (II) graded injury to the disc anulus, and (III) respiratory mechanics on the biomechanical response of the porcine L1-L3 vertebral unit (VU). In Experiments I and II, creep rate, modulus, and viscosity parameters were computed using a three-parameter solid rheological analysis of the displacement-time response recorded during the application of a 300-N load. In Experiment III, the effects of respiratory volume and frequency changes on disc pressure were assessed in the unloaded, statically loaded, and immobilized porcine VU. Our results indicated that the adult VU tended to be stiffer, deform or creep more slowly, and had a significantly higher viscosity than the VU of immature pigs. The results of Experiment I demonstrated that the biomechanical response for the VU was significantly altered by the death of the animal; the VU of the living animal (adolescent or mature) was more compliant and deformed at a faster rate than the VU of the same animal after death. Disc injury produced changes in stiffness, viscosity, and creep rate analogous to that of aging, and on the basis of the graded injuries created in this study, it appears that a small defect in the annulus is just as deleterious as removing a large section of anular material. The results of Experiment III indicated that respiration plays an important role in the normal, in vivo mechanical and nutritional behavior of the porcine VU. Altogether, these results demonstrate that, in the absence of normal physiologic conditions, one may not be able to reliably predict the mechanical response of the lumbar spine, and suggest that standards for the testing, handling, and storage of biologic tissue should be established.

Utilization of glucose and oxygen by the cells as well as concentration profiles of solutes were studied in the canine intervertebral disc. Cell metabolism in this avascular tissue, being predominantly anaerobic, was found to be dependent on oxygen tension (this being especially pronounced in the region of 0.13-0.4 kPa (1-3 mmHg). A high production rate of lactic acid was found in the nucleus pulposus, whereas towards the periphery of the annulus fibrosus this rate gradually decreased. In the centrally located areas of the disc tissue, far away from the blood circulation, the highest concentrations of lactic acid were found. For the normal disc the energy demands seem to be met as even small amounts of oxygen account for a large energy source, whereas the cellular requirements are balanced up predominantly by glucose. In regions with extremely low oxygen tensions large amounts of glucose are consumed, but an additional potential energy pool of glycogen seems to be available.

The metabolism of the canine nucleus pulposus was investigated at different oxygen tensions. It was found that even at high oxygen tensions the metabolism is mainly anaerobic, only approximately 1.5% of the glucose being converted to carbon dioxide. The concentration dependence of oxygen consumption is limited to very low oxygen tensions. Values of oxygen consumption and lactic acid production were used to calculate the concentration profiles of these substances within the nucleus pulposus, using a diffusion theory. The predicted concentration profiles were compared with the experimental measurements of concentration at various positions in the disc. The good agreement in these values found in the nucleus confirms that the main mechanism of metabolite transport is diffusion, and the main route of nutrient supply into the nucleus is via the endplate.

Adult dogs were injected intravenously with 35S-sulphate, and moderately exercised for one to six hours to measure isotope concentrations and profiles throughout the intervertebral discs. The isotope profiles were also observed in control animals that had been under anesthesia between injections and death. In both sets of animals, the profiles were in agreement with those expected for isotope transport by diffusion. This agreement indicates that fluid "pumping" during movement has an insignificant effect on transport of nutrients into the disc. Small solutes, e.g., O2, glucose, and sulphate, are transported into the disc chiefly by diffusion. However, calculations show that because of their low diffusivities, "pumping" may increase the rate of transport of large solutes into the disc, as it does in articular cartilage.

In this experiment study, we have investigated some transport and metabolic parameters of the canine intervertebral disc induced by spinal motion. The movements of the spine were obtained during supervised exercise, where either moderate, violent, or specific movements were performed. The results show changes in the metabolic rates as well as in concentration profiles of metabolites of the exercised groups in comparison to the control group. An increasing aerobic metabolism was noted in the outer part of the annulus and in the central part of the nucleus pulposus, resulting in a reduction of the lactate concentration. These findings do indicate that spinal movements, over a longer period of time give rise to positive nutritional variations. Furthermore, the reported changes might be of significance also for the human lumbar disc problem, since previous studies have demonstrated nutritional similarities between the discs of dogs and men.

A method for culturing intervertebral disc tissue in vitro under conditions that control changes in hydration and minimize loss of proteoglycans has been developed. Disc slices were enclosed in small-pore dialysis tubing and incubated in medium containing polyethylene glycol (PEG). By varying the PEG concentration, different external swelling pressures could be applied to the tissue. The rate of glycosaminoglycan synthesis in rabbit and dog disc was then measured using [35S]sulphate as a precursor. Synthesis rates varied with final hydration of the tissue, and the highest rates were found at hydrations close to those found in vivo. Under conditions of controlled hydration, rabbit nucleus has a higher rate of glycosaminoglycan synthesis than annulus. However, the rates measured in sagittal slices of dog disc decreased from the outer to the inner regions of the anterior annulus, reaching a minimum value in the nucleus and then increasing again in the posterior part of the annulus. The results show that in the intervertebral disc, measured rates depend on culture conditions.

The main mechanism for solute transport within the intervertebral disk is passive diffusion. The 2 routes for the exchange of solutes with the blood vessels outside the disk are via the periphery of the annulus, and through the end-plates. While the periphery of the annulus is completely permeable, the bone--disk interface is only partially so. In the region of the nucleus the effective area through which solute transport is taking place constitutes some 85% of the actual bone/disk interface; in the region of the inner annulus it is reduced to only 35% while the bone--disk interface at the outer annulus is almost completely impermeable. These figures, calculated from tracer diffusion experiments correlate very well with the qualitative observations of blood vessel contact. Apart from its dependence on the permeability of the endplate, solute diffusion is also determined by the nature of the solute. For example, a negatively charged solute such as the sulphate ion is considerably excluded from the nucleus, which limits its rate of penetration via the endplates. The sulphate uptake by the disk cells to produce glycosaminoglycans is low and comparable to that in articular cartilage.

We have in the present experimental study investigated the influence of cigarette smoking on some nutritional parameters of the porcine intervertebral disc. The results from the acute smoking tests show a significant reduction in solute transport. Diffusion of sulphate, oxygen and methyl glucose was reduced by 30-40 per cent. This effect was obtained after exposure to smoke for 20-30 minutes. A smoking period of three hours reduced the transport efficiency to about 50 per cent. The effect of smoking decreased when the exposure ceased. The concentration gradients were close to normal after 2 hours "recovery". These findings suggest that cigarette smoking not only significantly affects the circulatory system outside the intervertebral disc, where the most pronounced effect is the reduction in solute exchange capacity, but also significantly deteriorates the cellular uptake rate and metabolite production within the disc.

The viscoelastic properties of normal and surgically altered lumbar intervertebral disks from eight immature swine were examined in vivo. Rheological models were used to mathematically characterize the compressive creep-relation behavior of the disks before and after alteration by either chemonucleolysis [chymopapain (Chymodyactin) injection] or denucleation. In the normal disks, a significant modulating effect of respiration was observed that tended to increase the creep deformation response in comparison to that observed during similar in vitro and in situ studies. These results suggest that, in terms of assessing the absolute magnitude of the viscoelastic properties of lumbar disks, the influence of normal physiological function on adjacent vertebrae and surrounding tissues cannot be neglected. Preliminary results obtained from the experimentally altered disks indicated that partial denucleation primarily affected the initial stiffness behavior of the disk (24% decrease in elastic modulus), whereas chemonucleolysis caused changes in both the time-dependent (15% increase in creep rate) and instantaneous (23% decrease in elastic modulus) properties of the disk. Both partial denucleation and acute chemonucleolysis produced biomechanical changes that were comparable to grade II or slightly degenerative, age-related changes found in human lumbar intervertebral disks.

A polarographic membrane-covered electrode has been used for measurements of oxygen tension in the intervertebral disc. In vitro studies showed that the method measured partial pressures of oxygen with good reproducibility. However, in long continuous experiments, disc matrix adhering to the membrane influenced the readings negatively. The results of in vivo measurements in canine nucleus pulposus showed tensions of the order of 0.53 - 1.06 KPa (4 - 8 mm Hg). No significant variations between different disc levels were found.

Measurements of oxygen tension in the canine lumbar intervertebral disc, by the use of a polarographic oxygen electrode, were performed. The oxygen tension in the arterial blood was changed by regulating the oxygen concentration in the inspired air. The alterations in oxygen tension in the nucleus pulposus, as a function of distance to the vertebral endplate were determined. The response times registered in the disc matrix were relatively short (within five min.), which implies an efficient solute transport from the vertebral blood pool underneath the hyaline cartilage into the avascular intervertebral disc.