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)