Objective and Background: Interleukin 1 has been implicated in the progression of degenerative disc disease, however little data is available on the expression and production of IL-1 within degenerate discal cells. A few studies, have investigated herniated disc tissue but the results from these studies have been inconsistent. This study investigated the gene expression of IL-1 α, β, Ra and the receptor type I in discs removed at surgery from 7 prolapsed, 3 Scoliosis and 15 Degenerative discs (DD). In addition immunohistochemistry (IHC) was used to localise IL-1 α and IL-1 β within normal, and degenerate discs.

Methods: Human IVD tissue was obtained from disc replacement surgery and separated into nucleus pulposus (NP) and annulus fibrosus (AF) tissue, cell isolation using collagenase treatment was carried out, and RNA extraction on the cells performed immediately. Real time RT-PCR was then used to investigate gene expression of IL-1 gene family. IHC for IL-1 α and IL-1 β was also performed on paraffin embedded normal and degenerate disc samples.

Results: Expression of the IL-1 family genes was present at low levels within prolapsed disc samples. In contrast levels within scoliosis patents were the highest of the 3 disease states, however in both prolapsed discs and those from scoliosis patients a balance of IL-1 α/β to IL-1 Ra existed. Within samples from DD this balance was lost, with levels of IL-1 α and IL-1 β greatly exceeding levels of IL-1 Ra. In addition levels of IL-1 α and β showed an increase with age and were highest in those samples from the AF than the NP. IHC demonstrated both IL-1 α and IL-1 β protein within the NP and AF cells of the degenerate discs.

Conclusion: This study has demonstrated the mRNA expression of all members of the IL-1 family within IVD and in addition the chondrocytes within the disc produced IL-1 α and IL-1 β protein. The imbalance of IL-1 α/β to IL-1 Ra within those samples from degenerate discs but not prolapsed or scoliotic discs suggests a role for IL-1 within discal degeneration.

Aims: The intervertebral disc (IVD) consists of three structurally distinct areas; a nucleus pulposus (NP), annulus fibrosus (AF) and two cartilage endplates that together form a functional unit that allow flexibility of the spinal column and load transfer from adjoining vertebrae. The NP and AF contain cells that are phenotypically similar to chondrocytes found in articular cartilage. They also produce the 2 major matrix components aggrecan and collagen-type I and II. One feature of IVD degeneration is breakdown of the cartilage matrix. Using soluble growth factors could stimulate new matrix formation and help regenerate degraded discal cartilage. The aim of this study was to demonstrate the presence of four growth factor receptors within the IVD.

Methods and Results: Using immunohistochemsitry, we targeted expression of four growth factor receptors, (BMPRII, FGFR3, IGFR-1 and TGFβII), in biopsies taken from normal and degenerate IVD. Receptor expression was scored across regions of the disc using a peer-reviewed system that assessed the proportion of cells expressing a particular antigen and the average level of expression for those cells. For FGFR3, IGFR-1 and TGFβII, cells of the outer part of NP and inner AF expressed significantly higher receptor levels. The expression BMPRII deviated from that pattern and was present at higher levels in the inner and outer NP than in the AF. Although there were significant differences between FGFR3 expression in normal and degenerate biopsies, that was not the case for the other receptors. Growth factor receptor expression was also detectable on the ingrowing neurons and blood vessels that characterise part of the disease aetiology.

Conclusion: In conclusion, all of the receptors were found in the IVD, predominantly within the NP, suggesting that, addition of the ligands for these receptors may elicit a physiological response from disc chondrocytes.

MRI is a well-tolerated, short procedure that would provide an early, accurate and cost effective diagnosis in elderly patients with negative plain films and persistent post-traumatic hip pain, thereby facilitating their correct management.

It is 100% sensitive and specific to occult hip fractures and does not involve ionising radiation.

Fractured necks of femur in the elderly population are common. This group of patients are responsible for a significant proportion of health care costs and efforts today. The diagnosis of hip fractures is not always clear-cut and plain radiographs may not show an undisplaced fracture. The management of this patient group is dependant upon the correct diagnosis via imaging and treatment decisions are based on these findings. If these fractures are missed, there is a significant chance of displacement and avascular necrosis presenting at a later date. This would complicate matters and result in more complex surgery. This also increases health care costs due to an extra admission, more expensive and difficult surgery with longer rehabilitation and after care. In our study, the management of the patients reviewed was significantly altered due to the imaging process used.

We performed MRI scans on thirty-six patients who had post-traumatic hip pain and negative plain radiographs (reported as normal or equivocal). Twenty-three (64%) of the patients sustained a fracture, of which sixteen (44%) involved the neck of the femur, all of whom were above the age of 71 years. 100% of the elderly age group scanned were positive for a femoral neck fracture and eleven (31%) received operative intervention. The five patients who did not undergo operative management were deemed too unwell for surgery. Only three patients’ scans were negative.

These results confirm that MRI (in the 71 years and above age group), is indicated in order to diagnose an undisplaced fractured neck of femur not recognised on plain radiographs, which requires operative intervention in the form of dynamic hip screw or cannulated hip screws to prevent further deterioration or displacement.

Purpose and Background: We have previously reported our investigations of nerve ingrowth into intervertebral discs (IVD) from patients with mechanical low back pain. We have shown that in discs that are painful on discography (pain level discs) nerves actively grow into the deep annulus fibrosus and nucleus pulposus. Nerve ingrowth accompanies blood vessel ingrowth and advances into the nucleus pulposus from the end plate. The morphology and neurochemistry of these nerves indicate them to be nociceptive.

The growth of non-myelinated pain fibres in other settings is regulated by the cytokine Nerve Growth Factor (NGF). In this study, we have investigated the production and distribution of NGF, or more particularly its active isoform – NGF-β, and its receptors, in diseased intervertebral discs in order to establish whether this cytokine might be responsible for the observed nerve ingrowth in this situation.

Methods: Tissue sections of 21 pain level, 15 non-pain level diseased and 12 normal intervertebral discs, taken at the time of spinal surgery, and from cadavers, were probed by radioactive in situ hybridisation (ISH) for expression of NGF-β, and by immunohistochemistry (IHC) for its high and low affinity receptors (trk-A and p75 respectively). In addition, either serial sections were stained with cell specific markers (CD31 – endothelial cell, PGP9.5 – neurones, GAP43 – actively growing nerves) or sections were doubled stained (two antibodies or both ISH and IHC).

Results: We have demonstrated that NGF-β is synthesised by the endothelial cells of blood vessels growing into the IVD from the end plate. The high affinity receptor is expressed by those small nerve fibres that accompany the vessels and in their offshoots in pain level discs that are growing from perivascular nerves into the disc. In addition to their expressing the nerve specific molecule PGP9.5, the trk-A positive cells also express the nerve growth associated protein GAP43.

Conclusion: The data indicate that nerve ingrowth into IVD is regulated by NGF-β. We have localised this production to the endothelial cells of ingrowing blood vessels. NGF-β is a potential therapeutic target for the management of back pain.