The Role of Proteinases in the Progression of Osteoarthritis Neuropathy and its associated Pain.

Arthritis is ranked as the number one cause of disability in Canadian women, and number three in men. Osteoarthritis (OA) is the most common type of arthritis, affecting 1 in 10 Canadians. Remarkably, 60% of OA patients cite inadequate pain relief with current treatments. This is possibly because a third of arthritis patients develop neuropathic pain where the nerves innervating the affected joint are damaged. This type of pain is poorly controlled by drugs commonly prescribed to arthritis sufferers. We believe that the joints nerves are damaged, in part, by serine proteases-which are pro-inflammatory mediators found in arthritic joints. Using an injury model of OA, I will study the progression of knee joint damage and nerve injury, and determine if the use of drugs targeting serine proteases can provide pain relief once nerve damage has occurred. The activity of pain sensing nerve fibres in the joint will be recorded as an indicator of arthritic pain; increased nerve activity will indicate a higher likelihood of pain, and decreased nerve activity will indicate a lack of pain. The level of serine proteinases in arthritic patient's joints will be assessed to determine if the concentration and type of proteinases present correlate with the stage of the disease. This project will enhance our understanding of OA pain and reveal novel targets for the pharmacological treatment of OA pain with a neuropathic component.