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Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_17 | Pages 16 - 16
1 Apr 2013
Lama P Stefanakis M Sychev I Summers B Harding I Dolan P Adams M
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Introduction

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 via the annulus is confined to a) peripheral regions, and b) fissures extending into the annulus.

Methods

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).


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_4 | Pages 3 - 3
1 Jan 2013
Stefanakis M Luo J Truss A Finan C Dolan P Adams M
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Introduction

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 hypothesise that delamination is driven by high gradients of compressive stress in the annulus.

Methods

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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 95 - 95
1 Aug 2012
Stefanakis M Sychev I Summers B Dolan P Harding I Adams M
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Introduction

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.

Methods

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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 26 - 26
1 Aug 2012
Stefanakis M Luo J Pollintine P Ranken T Harris J Dolan P Adams MA
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Introduction

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.

Methods

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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 89 - 89
1 Aug 2012
Stefanakis M Luo J Pollintine P Dolan P Adams M
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Background

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).

Methods

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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_I | Pages 28 - 28
1 Jan 2012
Stefanakis M Luo J Harding I Dolan P Adams M
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Background

Fissures in the anulus fibrosus are common in disc degeneration, and are associated with discogenic pain. We hypothesise that anulus fissures are conducive to the ingrowth of blood vessels and nerves.

Purpose

To investigate the mechanical and chemical micro-environment of anulus fissures.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 488 - 489
1 Nov 2011
Stefanakis M Adams M Sharif M Gordon R Desmond G Ritchie A Kay A Harding I
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Background: Severe and chronic back pain often originates from degenerated intervertebral discs, probably from lesions in the outer posterior anulus. Unlike the nucleus, the outer anulus has a high cell density and adequate metabolite transport. The outer annulus can heal after injury in small and young experimental animals, but little is known about the healing potential of adult human discs.

Purpose: We seek evidence that healing of the human outer anulus follows the three stages of tendon healing: inflammation, repair, remodelling. If so, then manual therapy and self-treatment techniques known to facilitate tendon healing could be adapted to treat discogenic back pain.

Methods: Anulus tissue was removed at surgery (usually posteriorly) from 14 patients with discogenic back pain. Tissue was paraffin embedded and sectioned at 5 μm for histology and immunohistochemistry. Apoptosis was detected using an antibody for caspase-3.

Results: Fissures in the peripheral posterior annulus, and herniated tissue fragments, were associated with blood vessels, inflammatory cells, and with focal loss of proteoglycans. Cell density decreased with distance from fissures from the disc periphery. Overall cell density decreased with age. Apoptosis was greater in the nucleus than in the annulus, and was particularly associated with cell clusters, and with anulus fissures.

Conclusion: These preliminary results suggest an inflammatory healing response in the outer anulus, strongly associated with radial fissures. Loss of proteoglycan from fissure margins may facilitate the ingrowth of capillaries and nerves, which then stimulate local healing in the vicinity of the fissures.

Conflicts of Interest: None

Source of Funding: BackCare


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 487 - 487
1 Nov 2011
Stefanakis M Luo J Pollintine P Adams M
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Background: Neck muscles stabilise the head, but muscle tension imposes high compressive forces on the cervical spine. Little is known about which structures resist these high forces.

Purpose: To quantify compressive load-sharing within the cervical spine.

Methods: Seventeen cervical “motion segments” from cadavers aged 54–92 yr (mean 72 yr), were subjected to 200 N compression while positioned in simulated flexed and extended postures. Up to 5 Nm of bending was applied in various planes. Vertebral movements were recorded at 50 Hz using an optical MacReflex system. Tangent stiffness was calculated in compression and in bending. Load-sharing was evaluated from compressive stress measurements obtained by pulling a pressure transducer through the intervertebral disc. All measurements were repeated after 2 hr of creep loading at 150 N, and following sequential removal of the spinous process, apophyseal joints and uncovertebral joints.

Results: Most compression was resisted by the disc. However, creep increased compressive load-bearing by the neural arch, from 21% to 28% in flexed posture, and from 27% to 45% in extended posture, with most of this loading being resisted by the apophyseal joints. Uncovertebral joints resisted 10% of compression in extended posture, and 20% in flexed posture. Flexion and extension movements were resisted primarily by ligaments of the neural arch, and by the apophyseal joints, respectively, whereas lateral bending was resisted mostly by the apophyseal and uncovertebral joints.

Conclusion: Cervical apophyseal joints play a major role in compressive load-bearing, and also offer strong resistance to backwards and lateral bending. Uncovertebral joints primarily resist lateral bending.

Conflicts of Interest: None

Source of Funding: Scholarship from the Greek Government