The relationship between proteases, protease activated receptors and cytokines in mediating osteoarthritis pain

Osteoarthritis (OA) is the most common form of arthritis affecting 1 in 10 Canadians. The number one concern for OA sufferers is the alleviation of joint pain; however, current analgesics are either ineffective or produce toxic side-effects. Thus, there is a pressing need to discover novel drug targets to manage OA pain. During OA, enzymes are released into the joint which cause destruction of joint tissues. In addition to their digesting effects, these enzymes can also signal pain by acting on a unique group of receptors called PARs. This proposal will examine how these enzymes activate PARs in diseased joints to cause pain and disability. This work will improve our understanding of joint neurobiology and has the potential to uncover new approaches to effectively relieve OA pain.