This application is, in part, in response to PA-97-058, Research on Low Back Pain and Common Spinal Disorders (NIH Guide, Volume 26, Number 16, May 16, 1997). We wish to test the hypothesis that a high compressive force applied in vivo to the intervertebral disc affects the disc by one or both of two processes: 1) a compressive force causes an increase in hydrostatic pressure which affects the production of proteoglycans and collagen by the disc cells; 2) a compressive force causes remodeling of the endplate and a reduction in its transport properties. This hypothesis leads to:
Specific Aim 1. To determine which thresholds of force and time are required to produce 1) changes in matrix proteoglycan and collagen content, and 2) disc degeneration in its clearest clinical form.
Specific Aim 2. To demonstrate that a high compressive force applied to the intervertebral disc over a period of time affects structural changes in the cartilage endplate that in turn change the transport properties.
Specific Aim 3. To delineate which specific structures are responsible for changes in the transport properties of the cartilage endplate. This in vivo project is designed to provide key information regarding the relationship between applied compressive force, intervertebral disc cell metabolism, and pathologic changes in the disc within its natural environment. Such information will be necessary to develop preventive interventions for disc degeneration rather than focusing solely on the highly limited salvage treatment options that are available once advanced degeneration has already occurred. In particular, this study may help to better define the boundary discriminating beneficial from detrimental compressive force, thereby making it possible to avoid high levels of sustaining force that can initiate a cascade of events leading to disc degeneration. As such, we would have scientific evidence based on an in vivo study (not on in vitro or clinical or epidemiological studies) that would illustrate that heavy lifting or heavy physical work, or simply being overweight, is detrimental to healthy disc maintenance. We work towards our specific aims as follows: Coil springs will be tensioned and attached (to produce a compressive force) across the lumbar intervertebral discs of dogs and applied for up to 60 weeks, when the dogs will be killed. There are two unique features of this study: 1) coil springs produce a compressive force when stretched (i.e. fixed in extension), without restricting to any great extent, normal motion (flexion/extension/rotation); and 2) this is an in vivo study, therefore the biochemical response of the disc cells is not dependent on culture conditions normally associated with in vitro studies. After the dogs are killed the disc/endplates will be excised and assessed using immunohistochemistry (IHC) and enzyme-linked immunosorbent assays (ELISA).
