Aims

The aim of this study was to analyse human muscle tissue before and after rotator cuff repair to look for evidence of regeneration, and to characterise the changes seen in the type of muscle fibre.

This article reviews the current knowledge of the intervertebral disc (IVD) and its association with low back pain (LBP). The normal IVD is a largely avascular and aneural structure with a high water content, its nutrients mainly diffusing through the end plates. IVD degeneration occurs when its cells die or become dysfunctional, notably in an acidic environment. In the process of degeneration, the IVD becomes dehydrated and vascularised, and there is an ingrowth of nerves. Although not universally the case, the altered physiology of the IVD is believed to precede or be associated with many clinical symptoms or conditions including low back and/or lower limb pain, paraesthesia, spinal stenosis and disc herniation.

New treatment options have been developed in recent years. These include biological therapies and novel surgical techniques (such as total disc replacement), although many of these are still in their experimental phase. Central to developing further methods of treatment is the need for effective ways in which to assess patients and measure their outcomes. However, significant difficulties remain and it is therefore an appropriate time to be further investigating the scientific basis of and treatment of LBP.

Objectives: To examine and correlate the presence of neovascularisation, crystalline pyrophosphate deposits and other hisotological features in the disc and discogenic pain established by spinal probing and discography under aware state endoscopic visualisation.

Design: Tissue removed from intervertebral discs of 224 patients during surgery were examined by direct and polarised microscopy to identify the presence of calcium pyrophosphate and neovascularisation.

Material and Methods: Histology was correlated to the diagnostic provocative findings of spinal probing and discography, discal palpation during aware state endoscopy.

Results: Calcium Pyrophosphate: 20/224 (9%) patients demonstrated calcium pyrophosphate in the discs. Fourteen had pain reproduced on probing or discography; 13/20 (65%) of patients had either an annular collection or leak at the index level; 6/20 had an extradiscal cause of pain.

Neovascularisation: Thirty-seven out of 224 (16.5%) patients showed neovascularisation in the disc; four discs had crystalline pyrophosphate deposits; 33/37 (90%) had pain on probing and/or discography.

Conclusion: The presence of pyrophosphate in a disc without a tear or leak is not associated with annular tenderness. The presence of pyrophosphates in radial tears or leaks is associated with annular tenderness. Annular tears or leaks are not directly correlated to the presence of pyrophosphates. There is a high correlation between pain provocation and neovascularisation.

Background: Current treatments for Low back pain (LBP) are often empirical and few directed at the underlying disorder, altered discal cell metabolism, which precipitates the problem. The use of gene therapy to manipulate discal metabolism to treat LBP is an interesting possibility. The Intervertebral disc (IVD) is a therapeutic target in LBP, and one approach to gene therapy would be to isolate IVD chondrocytes (IVDC) and transfer genes Ex Vivo into these cells. Subsequent reinjection of these genetically altered cells into the lumbar IVD, would permit the expression of the trans-gene in vivo, generating the therapeutic protein within the IVD.

Methods: To test the viability of this approach, we isolated human IVDC from patients undergoing surgery, grew them Ex vivo and transfected them with the marker gene LacZ, using an adenovirus vector and the CMV promoter. Expression of the gene was then measured using X-gal staining for the gene product ~-galactosidase.

Results: IVDC infected with adenovirus/CMV-LacZ showed maximal LacZ expression 2 days post infection, with almost 50% of cells displaying X-gal positivity within monolayer cultures and 100% infection within alginate culture, gene expression was maintained up to 4 weeks and control cultures showed no LacZ expression.

Conclusion: This study shows that human IVDC can be transfected with a foreign gene using the adenovirus vector. The gene transduction of a therapeutic gene into IVDC, could provide long lasting effect. In addition the use of inducible promoters could allow for the autoregulation of gene expression.