Grant: Operating Grant

Over 4.6 million Canadians suffer from arthritis. This disease is a major cause of morbidity, disability and health care utilization, with an economic impact of about $33 billion annually. Osteoarthritis (OA) is the most common form of arthritis and affects more than 10 percent of Canadians. The most prominent yet least studied feature of OA is joint pain, characterized by spontaneous pain as well as pain during movements in the working range of the joint and during gentle pressure such as palpation. The mechanisms responsible for these symptoms are not fully understood, and current pain therapies have only limited effectiveness and their long-term use is precluded by unwanted negative side effects. There is therefore a need, from a health and economic standpoint, to identify new therapeutic targets in the treatment of arthritic pain. OA pain emanates from nerve fibers in the joint, termed articular afferents. It is now accepted that during OA, these fibers become hypersensitive to mechanical stimuli such as palpation and movement, yet the underlying mechanisms are unclear. Increasing our understanding of the molecular mechanisms underlying the sensitization of articular afferents could lead to the identification of new targets for therapeutic intervention in OA pain. Our project aims at defining the mechanisms underlying the sensitization of articular afferents in a mouse model of OA pain, with an emphasis on the role played by a subset of membrane proteins, termed mechanosensitive ion channels, specialized in sensing mechanical forces. We will use a combination of techniques including biology, electrophysiology, and behavioral testing of pain thresholds in a mouse model of OA pain. In addition to clarifying the role of these channels in physiology and pathology of articular afferents, our program will create new knowledge about fundamental aspects of sensory physiology, including pain transmission and how neurons sense mechanical forces.