Contribution of Proteases and Protease Activated Receptors to Joint Neuropathy and Arthritis Pain

At present, there are 4.6 million Canadians living with the pain of arthritis for which there are inadequate drug treatments. Current medications provide only limited pain relief and most drugs have significant negative side-effects. Thus, there is an urgent need to discover novel, more effective analgesics with low toxicity. During arthritis, enzymes are released into the joint which cause damage to the cartilage, bone and ligaments. In addition to the digesting effects of these enzymes, they can also signal pain and inflammation by acting on specific targets called PARs. We have shown that these PARs are present on nerves in the joint and we believe that one mechanism by which enzymes signal pain is by stimulating these PARs. We hypothesise that PAR activation can lead to nerve damage and consequently arthritis pain. In this project, we plan to identify the enzymes responsible for joint nerve injury and pain. We will also test drugs that block PARs to see if we can protect joint nerves from further damage and uncover a new way of alleviating arthritis pain.