DISCS has been involved in a number of Research projects regarding back pain ranging from imaging of the spine to understanding the basic changes at cellular level in a disc undergoing degeneration.


Completed Projects, Listed Chronologically

Magnetic Resonance Imaging Studies on the Role of Arterial Vascular Disease and Venous Obstruction in Intervertebral Disc Disease and Low Back Pain Impact of

Led by Professors G. Bydder & J. Hajnal at Imperial College London.

This project exceeded expectation in the technical development of imaging systems and made it possible for the first time to study and measure particles moving through the intervertebral disc.

Professor Bydder was awarded a prestigious Gold Medal from the Royal College of Radiologists for this work.

MRI Equipment Upgrade

Funding was provided to upgrade the scanning equipment at the Robert Steiner Magnetic Resonance Imaging Department at the Hammersmith Hospital in order to improve the quality of the MR Images.

How Does Disc Degeneration affect the Mechanical Integrity of the Annulus Fibrosus? Is the strong outer part of a disc worth saving if it is damaged?

Led by Dr M. Adams at the University of Bristol

This research project examined the structure of the intervertebral disc and was able to show that the strength of the outer annulus had no relationship to the compressive strength of the vertebra, suggesting that the real role of the outer annulus, or lining of the disc, may be as an intervertebral ligament rather than as a compressive load-bearing structure. This research identifies the dynamic role of the annulus which can be torn when a disc prolapses.

Study on Inappropriate Mechanical Stress and Intervertebral Discs Degeneration. Looking for the rate of disc degeneration caused by stresses such as jarring and lifting

Led by Dr Jill Urban, Physiology Dept, Oxford University

The digital camera obtained with the DISCS grant was of great help in examining cell viability and composition in diseased discs. It has shown that there is a significantly higher percentage of dead cells on the convex side of diseased discs and that there is a dense network of elastin in the discs, suggesting that elastin pays a mechanical role in the function of the disc.

Production of a research DVD

Led by Dr Clive Bromhall, scientific film specialist, Bristol.

Funding from DISCS lead to the production of a short film, making complex research understandable to the wider population and highlighting the ways in which research can lead to improved treatments for back pain sufferers.

Cell Senescence in degeneration of the Intervertebral Disc

Professor Judith A Hoyland, Tissue Injury and Repair, School of Medicine, The University of Manchester.

Ageing and degeneration of the intervertebral disc (IVD) is poorly understood. This lack of understanding is reflected in current treatment for the associated low back pain which is either symptomatic, or seeks to remove small parts of the disc or replace the damaged disc with bone (fusion) or an artificial disc, both of which are unsuccessful approaches in the long term. We believe that if more were known about the cellular processes of ageing and degeneration of the IVD novel therapies could be designed to target the underlying processes themselves. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. It is probable that this is due to accelerated cellular senescence (cells aging faster than expected) which causes fundamental changes in the ability of disc cells to maintain the IVD matrix thus leading to IVD degeneration and back pain.

To date our work, funded by DISCS, has shown that cell senescence occurs in vivo in the IVD and importantly appears to be accelerated in disc degeneration. Furthermore the senescent cell phenotype (observable characteristic) is associated with altered cell behaviour leading to the features that characterise disc degeneration (e.g. decreased matrix synthesis and increased matrix degradation/breakdown). We have shown that the senescence in IVD degeneration is probably due to stress induced senescence brought about by the up-regulation of a molecule known as caveolin -1. From our current understanding of the behaviour, biology, viability and life span of senescent cells this study has significance in the following areas:

i) At a basic scientific level to advance our understanding of the processes leading to disc degeneration

ii) In identifying potential new targets for intervening in the development of disc degeneration particularly the “stress events” leading to stress induced senescence; and

iii) in the design of new treatments for IVD degeneration, such as tissue engineering/regeneration, in which the plan is to stimulate existing native disc cells to manufacture new matrix or to use autologous IVD cells to populate biomatrices.

View from the DISCS Trustees

“This is a very important finding. Previous thinking was that disc degeneration was linked to aging. This research means that for the first time we may consider that disc degeneration in neither inevitable nor irreversible”.

Investigation into muscle fat and its effect on back pain

By Professor Alison McGregor PhD, MSc, MSCP, Professor in Biodynamics at Imperial College London.

Low back pain is a common, disabling, expensive and often chronic problem. Our understanding of how the spine works is limited, and consequently it can be difficult to identify which part of the lumbar spine contributes to the development of low back pain. It also makes advice about protection of the back difficult.

Increasingly the role of the spinal muscles in protecting the back has been highlighted, while impairments in the strength of these muscles have been noted in people with lower back pain. MRI scans indicate there is a high fat content in the muscles of people with back pain. Something that is not normally seen in healthy muscles. We have been exploring the muscles in patients having surgery for back and leg pain and we have found important changes in the muscle structure and content

Understanding spinal injury mechanisms

Research led by Professor Alison McGregor PhD, MSc, MSCP, Professor in Biodynamics at Imperial College London.

Low back pain and injury is a common problem amongst rowers. Our on-going studies have attempted to identify the mechanisms of injuries including studies to measure the motion of the back during rowing under a variety of work load conditions using a range of athletic skills from novice to elite. This project developed instrumentation on a rowing ergometer to understand the movements of the back as well as the forces being generated by the body. Using a mathematical model we can determine the loads being generated within the back. The image below gives an example of the force pattern generated at the seat during a single rowing stroke which will be integrated with information on how the rower is moving.

The impact of surgery to relieve leg pain on cortical control of trunk and leg muscles

Research led by Dr. Paul Strutton PhD, Principle’s Senior Lecturer in Anatomy & Professor Alison McGregor PhD, MSc, MSCP, form the Biodynamics Unit at Imperial College London.

Low back pain is an enormous problem in western society with social and financial costs high and still increasing. There are many studies which have implicated changes in the muscular system surrounding the spine as contributory to the formation of low back pain. Our studies have revealed that, in patients with chronic low back pain, there are changes in the pathways controlling movements from the brain to some of these muscles. However, it remains to be established if these changes contribute to, or are an adaptive change to the low back pain.
Surgery to relieve symptoms of back and leg pain is often undertaken when more conservative treatment options have had limited success. However, poor functional outcome and patient satisfaction with the return of symptoms in many patients warrant further investigation. It is not clear whether the changes within the brain pathways to the muscles that we have observed in chronic back and sciatica pain patients yet to undergo surgery can be reversed by such surgical intervention and whether those patients who recover best have the greatest changes in these pathways following the surgery. This work has provided novel insights into the changes occurring at the level of the central nervous system and which of these changes are reversed by surgery.

Current Research 2012- 2013

Dr Christine Le Maitre Senior Lecturer Sheffield Hallam University

Identification of differential intracellular signalling pathways between catabolic and anabolic factors in the intervertebral disc.

This study aimed to investigate whether different intracellular signalling pathways are activated by catabolic and anabolic factors in the intervertebral disc and how these can be targeted in selected therapeutic approaches.

The specific objectives of this study were to:

1. Elucidate the signalling pathways involved following CDMP-1 and IL-1 treatment of IVD cells.

2. Identify differential intracellular signalling pathways between anabolic and catabolic factors within the disc.

3. Investigate whether selective inhibition of differentially expressed signalling molecules can inhibit catabolic effects without affecting anabolic responses within the intervertebral disc.

Implications of findings:

Our work has demonstrated that whilst there are some pathways which are altered by catabolic and anabolic factors, a number of intracellular signalling pathways display an overlap between both these two pathways. Thus when choosing targets to inhibit in potential therapeutic treatment for low back pain it is essential to prevent unwanted inhibition and destruction of normal disc matrix production.

We have clearly demonstrated that different pathways are involved in the multitude of catabolic events triggered by the release of IL-1 and thus inhibiting a single pathway is not sufficient to inhibit the large number of catabolic events which are triggered by IL-1. However a combination of carefully selected inhibitors has the potential to inhibit all the catabolic events triggered during disc degeneration. This could hold real promise in inhibiting further degeneration in the early stages of degenerate discs.

Published abstracts from this work and conference presentations:

1. Intracellular Signalling Mechanisms Induced By Il-1 In Human Nucleus Pulposus Cells. Daniels, J, Phillips, KLE, Chiverton, N, Le Maitre, CL. 2012 Rheumatology: 51(3): 145-145.

2. Differential Intracellular Signalling Pathways Induced by IL-1 and CDMP-1 in Human Nucleus Pulposus Cells, and their Potential as Therapeutic Targets. : J Daniels; KL Phillips; A Cole; A Michael; L Breakwell; N Chiverton; CL Le Maitre. 2012 J. Path. 228, S1:17

3. Intracellular signalling mechanisms induced by IL-1 in human nucleus pulposus cells. Phillips K. L. E., Chiverton N., Le Maitre C. L. Philadelphia Spine Meeting (Philadelphia, USA, Nov 2011).

4. Differential intracellular signalling pathways are activated by catabolic and anabolic factors in the IVD, and these could be targeted in selected therapeutic approaches. Daniels J, Phillips K. L. E., Chiverton N,* Le Maitre C. L World Forum for Spine Research: The Intervertebral Disc—from Degeneration to Pain (Helsinki, Finland, June 2012).

Papers related to this work:

Inflammatory Cytokines Induce Notch Signalling Activity in Nucleus Pulposus Cells. H. Wang, Y. Tian, J. Wang, K.L.E Phillips, A.L.A. Binch, S. Dunn, A. Cross, N. Chiverton, Z. Zheng, I.M. Shapiro, C.L. Le Maitre, M.V. Risbud. Submitted to Journal of Biological Chemistry. December 2012.

Differential Intracellular Signalling Pathways Induced by IL-1 and CDMP-1 in Human Nucleus Pulposus Cells, and their Potential as Therapeutic Targets. : J Daniels; KL Phillips; A Cole; A Michael; L Breakwell; N Chiverton; CL Le Maitre. (Under preparation)

New Proposals by Dr. Le Maitre from Sheffield Hallam University

Requires Funding

Targeting differential signalling pathways for novel treatments for Low Back Pain.

Low back pain is a major cause of morbidity worldwide and it is estimated 40% of chronic low back pain cases are a direct result of degeneration of the intervertebral discs in the spine.

Normal intervertebral discs contain a small population of cells, which are similar to those seen in cartilaginous tissues which produce the matrix and remodel it via the production of a number of selective enzymes. In the normal disc the balance between anabolic (matrix production) and catabolic (breakdown) processes are carefully balanced.

During degeneration this balance is lost in favour of the catabolic process which leads to degradation of the intervertebral disc matrix, infiltration of blood vessels and nerves and release of small molecules known as cytokines which sensitise nerves to pain.

Our previous work supported by DISCS identified a number of pathways which are activated inside the cells following anabolic and catabolic stimuli. Some of the pathways overlap between catabolic and anabolic stimuli however we identified three potential pathways which appear selective to the catabolic processes. We therefore wish to investigate the ability to inhibit these selective pathways and determine the ideal combination of inhibitors required to prevent all abnormal catabolic events without affecting anabolic processes. This approach could hold real promise in helping us to inhibit further degeneration in the early stages of disc disease and also create the correct tissue niche to promote regeneration of the intervertebral disc.