Discogenic pain is associated with ingrowth of blood vessels and nerves, but uncertainty over the extent of ingrowth is hindering development of appropriate treatments. We hypothesise that adult human annulus fibrosus is such a dense crosslinked tissue that ingrowth Disc tissue was examined from 61 patients (aged 37–75 yrs) undergoing surgery for disc herniation, degeneration or scoliosis. 5 µm sections were stained with H&E to identify structures and tissue types. 30 µm frozen sections were examined using confocal microscopy, following immunostaining for CD31 (an endothelial cell marker), PGP 9.5 and Substance P (general and nociceptive nerve markers, respectively). Fluorescent tags were attached to the antibodies. ‘Volocity’ software was used to calculate numbers and total cross-sectional area of labelled structures, and to measure their distance from the nearest free surface (disc periphery, or annulus fissure).Introduction
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Delamination of the annulus fibrosus is an early feature of disc degeneration, and it allows individual lamellae to collapse into the nucleus, or to bulge radially outwards. We 102 thoracolumbar motion segments (T8-9 to L5-S1) were dissected from 42 cadavers aged 19–92 yrs. Each specimen was subjected to 1 kN compression, while intradiscal compressive stresses were measured by pulling a pressure transducer along the disc's mid-sagittal diameter. Stress gradients were measured, in the anterior and posterior annulus, as the average rate of increase in compressive stress (MPa/mm) between the nucleus and the region of maximum stress in the annulus. Average nucleus pressure was also recorded. Disc degeneration was assessed macroscopically on a scale of 1–4.Introduction
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Severe ‘discogenic’ back pain may be related to the ingrowth of nerves and blood vessels, although this is controversial. We hypothesise that ingrowth is greater in painful discs, and is facilitated in the region of annulus fissures. We compared tissue removed at surgery from 22 patients with discogenic back pain and/or sciatica, and from 16 young patients with scoliosis who served as controls. Wax-embedded specimens were sectioned at 7μm. Nerves and blood vessels were identified using histological stains, and antibodies to PGP 9.5 and CD31 respectively.Introduction
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The feature of disc degeneration most closely associated with pain is a large fissure in the annulus fibrosus. Nerves and blood vessels are excluded from normal discs by high matrix stresses and by high proteoglycan (PG) content. However, they appear to grow into annulus fissures in surgically-removed degenerated discs. We hypothesize that anulus fissures provide a micro-environment that is mechanically and chemically conducive to the in-growth of nerves and blood vessels. 18 three-vertebra thoraco-lumbar spine specimens (T10/12 to L2/4) were obtained from 9 cadavers aged 68-92 yrs. All 36 discs were injected with Toluidine Blue so that leaking dye would indicate major fissures in the annulus. Specimens were then compressed at 1000 N while positioned in simulated flexed and extended postures, and the distribution of compressive stress within each disc was characterised by pulling a pressure transducer through it in various planes. After testing, discs were dissected and the morphology of fissures noted. Reductions in stress in the vicinity of fissures were compared with average pressure in the disc nucleus. Distributions of PGs and collagen were investigated in 16 surgically-removed discs by staining with Safranin O. Digital images were analysed in Matlab to obtain profiles of stain density in the vicinity of fissures.Introduction
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In the annulus fibrosus of degenerated intervertebral discs, disruption to inter-lamellar cross-ties appears to lead to delamination, and the development of anulus fissures. We hypothesise that such internal disruption is likely to be driven by high gradients of compressive stress (i.e. large differences in stress from the nucleus to the mid anulus). Eighty-nine thoracolumbar motion segements, from T7/8 to L4/5, were dissected from 38 cadavers aged 42-96 yrs. Each was subjected to 1 kN compressive loading, while intradiscal compressive stresses were measured by pulling a pressure transducer along the disc's mid-sagittal diameter. Measurements were repeated in flexed and extended postures. Stress gradients were measured, in the anterior and posterior anulus of each disc, as the average rate of increase in stress (MPa/mm) between the nucleus and the region of maximum compressive stress in the anulus. Average nucleus pressure (IDP) was also recorded.Background
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