Grant: Operating Grant

Introduction: At present little is known about the molecular mechanisms involved in pain generation associated with intervertebral discs degeneration. At least two different mechanisms or a combination of the two could potentially lead to tissue breakdown and to the release of factors resulting in pain from the intervertebral disc. The aim of this study is to identify and understand mechanisms that may lead to painful intervertebral discs and to find ways to block the pain mediators. We will use a model system where we subject intact intervertebral discs to varying degree of load to understand the effect of adverse load. Isolated disc and nerve cells will then be used to study and block specific factors or pathways. Significance to human health:The term discogenic low back pain was coined more than 30 years ago to describe pain associated with disc degeneration, which currently represents an enormous socio-economic cost to the healthcare systems in developed countries. Despite the burden of disease there are no effective diagnostic tools to identify the early degenerative changes in intervertebral discs that result in pain. An improved understanding of the pathophysiology leading to discogenic low back pain will facilitate the development of biomarkers as targets for more specific therapeutic interventions for pain relief, so avoiding invasive and often dangerous surgical procedures.