The role of antibiotics in the treatment of disc-space infection is controversial. This study assessed the tissue penetration of flucloxacillin and cephradine into the normal intervertebral disc after intravenous administration of a bolus dose of antibiotic. Twenty-five discs were removed from 12 adolescent patients having anterior spinal surgery to correct scoliosis; antibiotic had been administered between 30 minutes and four hours before operation. Despite high blood levels, no antibiotic could be detected by bioassay or by high-pressure liquid chromatography (h.p.l.c.) in any of the specimens from the nucleus pulposus or the annulus fibrosus

The belief that an intervertebral disc must degenerate before it can herniate has clinical and medicolegal significance, but lacks scientific validity. We hypothesised that tissue changes in herniated discs differ from those in discs that degenerate without herniation. Tissues were obtained at surgery from 21 herniated discs and 11 non-herniated discs of similar degeneration as assessed by the Pfirrmann grade. Thin sections were graded histologically, and certain features were quantified using immunofluorescence combined with confocal microscopy and image analysis. Herniated and degenerated tissues were compared separately for each tissue type: nucleus, inner annulus and outer annulus. Herniated tissues showed significantly greater proteoglycan loss (outer annulus), neovascularisation (annulus), innervation (annulus), cellularity/inflammation (annulus) and expression of matrix-degrading enzymes (inner annulus) than degenerated discs. No significant differences were seen in the nucleus tissue from herniated and degenerated discs. Degenerative changes start in the nucleus, so it seems unlikely that advanced degeneration caused herniation in 21 of these 32 discs. On the contrary, specific changes in the annulus can be interpreted as the consequences of herniation, when disruption allows local swelling, proteoglycan loss, and the ingrowth of blood vessels, nerves and inflammatory cells. In conclusion, it should not be assumed that degenerative changes always precede disc herniation. Cite this article: Bone Joint J 2013;95-B:1127–33

Computerised tomography of the lumbar spine was performed on 22 patients with clinical evidence of prolapse of an intervertebral disc and normal or equivocal radiculograms. Of 11 patients with positive scans who had an operation the presence of pathology was confirmed in 10. Although CT scanning is always helpful in diagnosing disc disorders, where facilities are scarce (as in Great Britain) it is best employed in patients with negative or non-contributory radiculography

Two groups of intervertebral discs, one normal, as obtained from the post-mortem room, the other prolapsed, as removed at operation, have been compared by chemical analysis of their principal constituents. There is a progression of chemical changes associated with the ageing of the normal disc. This shows not only the expected slight increase in collagen as age advances, but also, surprisingly, that the polysaccharide content rises to a maximum in the fourth decade, in the same way as does polysaccharide in costal cartilage. In prolapsed discs the ageing process is superseded by a different and distinctive progression, which advances, not according to age, but according to the duration of the prolapse. There is a critical level to which the polysaccharide content must apparently fall, irrespective of the normal level for the patient's age, before a prolapse occurs. Normal ageing probably consists in the breakdown of a particular polysaccharide/protein linkage, with coincident "maturation" of collagen. In the prolapsing disc multiple, and possibly different, linkages are rapidly broken down. This depolymerisation of a gel structure must be presumed to be the basis of the decreased imbibition capacity of the nucleus pulposus, and to be the source of the hydrostatic abnormalities which result in disc prolapse. In both normal and prolapsing discs the products of mucopolysaccharide breakdown appear to participate in the metabolism of collagen

By polarising microscope and x-ray crystallographic techniques the annulus fibrosus has been shown to consist of regularly oriented sheets of collagen fibres. These results have been interpreted in terms of an elastic mechanism whereby thrust from the nucleus causes increased girth in the annulus. It is suggested that this is accomplished by a change in the angle between the axis of the fibres in adjacent uniaxial layers of the annulus. Furthermore, the loss of elasticity of the intervertebral disc associated with age would seem to be mainly due to changes occurring in the nucleus pulposus

Our study establishes a rabbit model of disc degeneration which requires neither a chemical nor physical injury to the disc. Disc degeneration similar to that seen in man was created at levels proximal (L4-L5) and caudal (L7-S1) to a simulated lumbar fusion and was studied for up to nine months after arthrodesis. Loss of the normal parallel arrangement of collagen bundles within the annular lamellae was observed in intervertebral discs adjacent to the fusion at three months. By six months there was further disorganisation as well as loss of distinction between the lamellae themselves. By nine months the structure of the disc had been replaced by disorganised fibrous tissue, and annular tears were seen. There was an initial cellular proliferative response followed by loss of chondrocytes and notochordal cells in the nucleus pulposus. Degeneration was accompanied by a decrease in the monomer size of proteoglycans. Narrowing of the disc space, endplate sclerosis and the formation of osteophytes at adjacent disc spaces were observed radiologically

We studied degenerative changes in the cervical intervertebral discs of 497 asymptomatic subjects by MRI and evaluated disc degeneration by loss of signal intensity, posterior and anterior disc protrusion, narrowing of the disc space and foraminal stenosis. In each subject, five disc levels from C2–C3 to C6–C7 were evaluated. The frequency of all degenerative findings increased linearly with age. Disc degeneration was the most common observation, being present in 17% of discs of men and 12% of those of women in their twenties, and 86% and 89% of discs of both men and women over 60 years of age. We found significant differences in frequency between genders for posterior disc protrusion and foraminal stenosis. The former, with demonstrable compression of the spinal cord, was observed in 7.6% of subjects, mostly over 50 years of age. Our results should be taken into account when interpreting the MRI findings in patients with symptomatic disorders of the cervical spine

A new technique for the transthoracic removal of a prolapsed intervertebral disc in the mid or lower thoracic spine is described. Investigations before operation include thoracic myelography, selective spinal angiography and CT scanning. Image intensification is used at operation to check the level of the prolapse. A tunnel in the coronal plane (vertebrotomy) is made through the posterolateral part of the disc and the adjacent vertebral bodies, to reach the spinal canal at the site of the prolapse. This gives good exposure and enables gentle removal of the disc prolapse and any associated osteophytes, under direct vision without need for retraction or pressure on the dura or spinal cord. Spinal stability is not compromised, and the blood supply of the cord is not disturbed. Five consecutive patients are reported, including one in whom the disc prolapse was calcified and had herniated into the spinal cord. All were treated successfully

We studied the presence of anabolic growth factors in human herniated intervertebral discs (IVD) using a reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Messenger RNA (mRNA) was isolated from the nucleus pulposus using oligo (dT). 25. superparamagnetic beads and probing with gene-specific primers in RT-PCR. mRNA coding for TGF-α (3/10), EGF (0/10), TGF-β1 (0/10) and TGF-β3 (2/10) or the EGF receptor (EGF-R; 0/10) and TGF-β type-II receptor (0/10) was found only occasionally. Beta-actin was always present and positive sample controls confirmed the validity of the RT-PCR assay. These RT-PCR findings were confirmed using immunohistochemical staining of EGF and TFG-β, whereas TGF-α protein was always found associated with discocytes. We conclude that the nucleus pulposus of the herniated IVD is vulnerable to proteolytic degradation and depletion of proteoglycans due to the lack and/or low production of anabolic growth factors/receptors which could increase the local synthesis of the extracellular matrix

Doubt remains as to the safest surgical approach to the prolapsed thoracic intervertebral disc. Laminectomy, lateral rhachotomy and the transthoracic approach all have their protagonists. Twenty-two patients from the National Hospital for Nervous Diseases, Queen Square, and Atkinson Morley's Hospital have been reviewed. Their clinical presentation is discussed and the ancillary aids to diagnosis assessed. The diagnostic value of disc space calcification is stressed, and the use of air myelography as an adjunct to positive contrast myelography is noted. Fifteen patients were subjected to laminectomy, and seven to lateral rhachotomy. Each group contained patients with a wide range of neurological deficit. Six of the patients who underwent laminectomy were improved, two were unchanged, six deteriorated and one died. Of the patients who had lateral rhachotomy, six were improved, one was unchanged and none deteriorated. The conclusion is drawn that lateral rhachotomy is a safer procedure

1. The uptake of S. 35. labelled sodium sulphate has been studied autoradiographically in the intervertebral disc of the young rabbit. 2. The sojourn of the isotope in the tissues includes an intracellular phase of approximately twenty-four hours, followed by an extracellular phase. 3. The cells exhibiting by far the greatest affinity for the sulphate ion are the peripheral groups of cells of the nucleus pulposus, while the chondrocyte-like cells of the cartilaginous segment of the annulus fibrosus are also fairly active. The central cells of the nucleus and the fibroblasts of the outer one-third of the annulus have a much lower uptake. 4. By analogy with similar studies on hyaline cartilage, and on the basis of correlation between the alcinophilia of the tissues and the concentration of the label, both before and after hyalase digestion of the tissue, it is considered that in the young rabbit disc, as in articular cartilage, the sulphate is incorporated primarily into chondroitin sulphate. 5. The elimination of the isotope from the nucleus at twenty-four days and the persistence of the label in the annulus fibrosus at thirty-two days tends to suggest that the metabolic turnover of acid mucopolysaccharide is considerably slower in the annulus than in the nucleus

We have studied the ability of a range of antibiotics to penetrate intervertebral disc tissue in vitro, using a mouse disc model. Equilibrium concentrations of antibiotics incorporated into the entire disc were determined by bioassay using a microbial growth-inhibition method. Uptake was significantly higher with positively-charged aminoglycosides compared with negatively-charged penicillins and cephalosporins. Uncharged ciprofloxacin showed an intermediate degree of uptake. Our results support the hypothesis that electrostatic interaction between charged antibiotics and negatively-charged glycosaminoglycans in the disc is an important factor in antibiotic penetration, and may explain their differential uptake

We report the cases of teenage twin girls presenting within months of each other with severe symptoms from lumbosacral disc prolapses, requiring laminectomy in one and chemonucleolysis in the other. CT scans showed similarities in spinal configuration, including the presence of disc bulges at the L4-5 level. This suggests a strong hereditary factor in prolapse of intervertebral discs, but a review of the literature showed little information on that aspect

Herniated intervertebral disc tissue has been shown to produce a number of proinflammatory mediators and cytokines, but there have been no similar studies using discs from patients with discogenic low back pain. We have compared the levels of production of interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E. 2. (PGE. 2. ) in disc tissue from patients undergoing discectomy for sciatica (63) with that from patients undergoing fusion for discogenic low back pain (20) using an enzyme-linked immunoabsorbent assay. There was a statistically significant difference between levels of production of IL-6 and IL-8 in the sciatica and low back pain groups (p < 0.006 and p < 0.003, respectively). The high levels of proinflammatory mediator found in disc tissue from patients undergoing fusion suggest that production of proinflammatory mediators within the nucleus pulposus may be a major factor in the genesis of a painful lumbar disc

It has been suggested that matrix metalloproteinase-3 (MMP-3, stromelysin-1) has an important role in the degeneration of intervertebral discs (IVDs). A human MMP-3 promoter 5A/6A polymorphism was reported to be involved in the regulation of MMP-3 gene expression. We suggest that IVD degeneration is associated with 5A/6A polymorphism. We studied 54 young and 49 elderly Japanese subjects. Degeneration of the lumbar discs was graded using MRI in the younger group and by radiography in the elderly. 5A/6A polymorphism was determined by polymerase-chain reaction-based assays. We found that the 5A5A and 5A6A genotype in the elderly was associated with a significantly larger number of degenerative IVDs than the 6A6A (p < 0.05), but there was no significant difference in the young. In the elderly, the IVD degenerative scores were also distributed more highly in the 5A5A and 5A6A genotypes (p = 0.0029). Our findings indicate that the 5A allele is a possible risk factor for the acceleration of degenerative changes in the lumbar disc in the elderly

To clarify the pathomechanisms of discogenic low back pain, the sympathetic afferent discharge originating from the L5-L6 disc via the L2 root were investigated neurophysiologically in 31 Lewis rats. Sympathetic afferent units were recorded from the L2 root connected to the lumbar sympathetic trunk by rami communicantes. The L5-L6 discs were mechanically probed, stimulated electrically to evoke action potentials and, finally, treated with chemicals to produce an inflammatory reaction. We could not obtain a response from any units in the L5-L6 discs using mechanical stimulation, but with electrical stimulation we identified 42 units consisting mostly of A-delta fibres. In some experiments a response to mechanical probing of the L5-L6 disc was recognised after producing an inflammatory reaction. This study suggests that mechanical stimulation of the lumbar discs may not always produce pain, whereas inflammatory changes may cause the disc to become sensitive to mechanical stimuli, resulting in nociceptive information being transmitted as discogenic low back pain to the spinal cord through the lumbar sympathetic trunk. This may partly explain the variation in human symptoms of degenerate discs.

Previous studies on the anatomy of the lumbar spine have not clarified the precise relationship of the origin of the lumbar roots to their corresponding discs or their angulation to the dural sac. We studied 33 cadavers (25 formalin-preserved and eight fresh-frozen) and their radiographs to determine these details.

All cadavers showed a gradual decrease in the angle of the nerve root from L1 to S1. The origin of the root was found to be below the corresponding disc for the L1 to L4 roots. In the formalin-preserved cadavers 8% of the L5 roots originated above, 64% below and 28% at the L4/L5 disc. In the fresh cadavers the values were 12.5%, 62.5% and 25%, respectively. For the S1 root 76% originated above and 24% at the L5-S1 disc in the formalin-preserved cadavers and 75% and 25%, respectively, in the fresh cadavers.

A herniated disc usually compresses the root before division of the root sleeve. Thus, compression of the thecal sac before the origin of the root sleeve is common for L1 to L5 whereas compression at the root sleeve is common for S1.

Our findings are of value in understanding the pathophysiology of prolapse of the disc and in preventing complications during surgery.

We studied 52 patients, each with a lumbosacral transitional vertebra. Using MRI we found that the lumbar discs immediately above the transitional vertebra were significantly more degenerative and those between the transitional vertebrae and the sacrum were significantly less degenerative compared with discs at other levels. We also performed an anatomical study using 70 cadavers. We found that the iliolumbar ligament at the level immediately above the transitional vertebra was thinner and weaker than it was in cadavers without a lumbosacral transitional vertebra.

Instability of the vertebral segment above the transitional vertebra because of a weak iliolumbar ligament could lead to subsequent disc degeneration which may occur earlier than at other disc levels. Some stability between the transitional vertebra and the sacrum could be preserved by the formation of either an articulation or by bony union between the vertebra and the sacrum through its transverse process. This may protect the disc from further degeneration in the long term.

The anatomical studies, basic to our understanding of lumbar spine innervation through the sinu-vertebral nerves, are reviewed. Research in the 1980s suggested that pain sensation was conducted in part via the sympathetic system. These sensory pathways have now been clarified using sophisticated experimental and histochemical techniques confirming a dual pattern. One route enters the adjacent dorsal root segmentally, whereas the other supply is non-segmental ascending through the paravertebral sympathetic chain with re-entry through the thoracolumbar white rami communicantes.

Sensory nerve endings in the degenerative lumbar disc penetrate deep into the disrupted nucleus pulposus, insensitive in the normal lumbar spine. Complex as well as free nerve endings would appear to contribute to pain transmission.

The nature and mechanism of discogenic pain is still speculative but there is growing evidence to support a ‘visceral pain’ hypothesis, unique in the muscloskeletal system. This mechanism is open to ‘peripheral sensitisation’ and possibly ‘central sensitisation’ as a potential cause of chronic back pain.