Article

Low back pain carries an enormous socioeconomic burden. Current treatment
modalities for symptomatic intervertebral disk (IVD) degeneration have limited
and often inconsistent clinical benefits. Novel approaches with the potential to
halt or even reverse disk degeneration and restore physiologic disk function,
such as biological treatments, are therefore very attractive.
The following
barriers are impeding the development of successful therapeutic interventions:
(1) the biology and pathophysiology of disk degeneration are not well understood,
and (2) the precise relationship between IVD degeneration and low back pain
remains unclear. This article reviews the structural changes that take place
during IVD degeneration and their relationship to diskogenic back pain. It also
presents treatment modalities that currently are under laboratory investigation
and are being studied in clinical trials. The authors of recent studies have
shown that the content of large proteoglycans, such as aggrecan and versican,
decreases with aging and IVD degeneration, whereas the content of certain small
proteoglycans, such as biglycan, increases. Proinflammatory cytokines such as
interleukin-1 and tumor necrosis factor-alpha also are associated with IVD
degeneration and are potential biomarkers of IVD degeneration and repair. Our
group of investigators and others have developed in vitro models of IVD cell and
explant culture in addition to in vivo animal models to study IVD degeneration
and repair. With the use of these models, we have tested candidate therapeutic
agents to assess their therapeutic potential for matrix restoration. When a
rabbit annular puncture model of IVD degeneration was used, injections of either
bone morphogenetic protein-7 (also known as osteogenic protein-1) or bone
morphogenetic protein-14 (also known as growth differentiation factor-5) were
shown to be effective in restoring IVD structures. On the basis of these data,
the Food and Drug Administration has recently allowed the initiation of
Investigational New Drug clinical trials on osteogenic protein-1 and growth
differentiation factor-5 in the United States. Protein therapies such as other
growth factors, inhibitors of degradation enzymes or cytokines, and cell
therapies also are being investigated in laboratory settings with the goal of
restoring disk function and alleviating back pain symptoms. These therapies may
be used by physiatrists with the skills required to administer intradiskal
injections and supervise a comprehensive rehabilitation program after the
procedures. Ultimately, the clinical use of any biological treatment discussed in
this article would require the collective efforts of clinicians and researchers.
CI - Copyright (c) 2011 American Academy of Physical Medicine and Rehabilitation.
Published by Elsevier Inc. All rights reserved.

Langue : ANGLAIS