The Cellular Pathobiology of the Degenerate Intervertebral Disc and Discogenic Back Pain

A. J. Freemont


Rheumatology. 2009;48(1):5-10. 

In This Article

Abstract and Introduction


In 2007, three times as many peer reviewed publications covering the biology and biotherapeutics of intervertebral disc (IVD) disease appeared in the literature than in 1997. This is testimony to the upsurge in interest in the IVD, mainly driven by the openings that modern molecular pathology has generated to investigate mechanisms of human disease and the potential offered by novel therapeutic technologies to use data coming from these studies to positively influence chronic discogenic back pain and sciatica. Molecular pathology has shown IVD degeneration, a major cause of low back pain, to be a complex, active disorder in which disturbed cytokine biology, cellular dysfunction and altered load responses play key roles. This has translated into a search for target molecules and disease processes that might be the focus of future, evidence-based therapies for back pain. It is not possible to describe the totality of advances that have been made in understanding the biology of the IVD in recent years, but in this review those areas of biology that are currently influencing, or could conceivably soon impinge on, clinical thinking or practice around IVD degeneration and discogenic back pain are described and discussed.


It is estimated that more than half the population will experience significant low back pain (LBP) during their lives.[1] LBP is a major cause of morbidity and impacts considerably on the economy, both through loss of work (~15% of all sickness leave in the United Kingdom) and the cost of health care and societal support for the affected individual and their family.[2,3]

Although an important public health issue, the pathogenesis of LBP is poorly understood. Most is thought to arise from disturbances in the lumbar spine and associated structures. Studies examining the problem from different directions (e.g. examination of volunteers[4] and patients,[5] imaging investigations,[6] trials of intervention [7]) have produced evidence implicating the intervertebral disc (IVD) in a significant proportion (at least 40%) of cases of chronic back pain, leading to the use of the term 'discogenic back pain'.

From the work that has been carried out to date two processes stand out as being important in the origins of discogenic back pain, disc degeneration and nociceptive nerve ingrowth into the normally aneural IVD.

Only in the last 10-15 yrs have the mechanisms underlying human IVD degeneration been studied in any detail, but the arrival of molecular pathology and similar techniques for examining disease mechanisms in human tissue (e.g. immunohistochemistry,[8] in situ zymography,[9]in situ hybridization[10] and quantitative image analysis [11]) and the advent of biotherapeutics,[12] stem cell therapy[13] and tissue engineering[14] have brought both methods for and reasons to investigate IVD degeneration.

During these studies it became evident that there was vascular ingrowth into the degenerate IVD and that in painful degenerate IVD the vessels were accompanied by nociceptive nerves. Further investigation is required, but if it transpires that nociceptive nerve ingrowth is a major cause of discogenic back pain, the processes driving this ingrowth could become key therapeutic targets for its management.

To understand the pathology and pathogenesis of IVD degeneration and discogenic back pain, it is first necessary to have an overview of the normal IVD and IVD cell function.


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