Grant: Project Grant

Back pain arising from intervertebral disc degeneration (IVD) is the second most common medical condition in North America and worldwide. Intervertebral disc degeneration has a major negative impact on the quality of life, and in the United States alone, accounted for an estimated cost of up to 238 billion dollars in 2013. Despite the prevalence, little is known about the molecular mechanisms leading to intervertebral disc degeneration and its associated pain. As there are no conservative treatment options available, patients presenting with advanced stages of the disease require invasive surgery to relieve pain. It is well known that the matrix properties change as a result of degeneration, however, it is less clear how this is initiated and how it could be prevented. Previous work: Our previous work has demonstrated that degenerating and painful human IVDs release increased levels of factors that can affect nerve growth and induce pain. We have established that injury to human IVDs can initiate the factors associated with degeneration and back pain. We have also demonstrated an increase in toll-like receptor expression as a result of injury. Proposed study: We propose to evaluate if Toll-Like Receptor expression and signalling is directly associated with intervertebral disc degeneration and the development of chronic pain. We will evaluate if matrix fragments called "alarmins" promote expression and activation of Toll-Like Receptors. Finally we aim to evaluate if drugs targeting Toll-Like Receptors will halt the progression of degeneration and pain. Significance to Human Health: An expanded knowledge of the aetiology and pathogenesis of intervertebral disc degeneration will lead to improved therapeutic interventions and ultimately decrease pain and improve the quality of life of patients living with intervertebral disc degeneration