Grant: Project Grant

Pain with motion, pain at rest, pain at night, sharp pain, dull pain-pain is highly variable among and within those afflicted with arthritis. Much is now known about joint tissue changes in arthritis, but only a little is known about how pain that begins in the joint makes its way to the spinal cord and brain, and what happens along these pathways. The release of harmful factors in arthritic joints gets interpreted as painful sensations, which pass through specific sensory nerves that extend from the joint to the spinal cord. To be perceived as pain, sensations must be further communicated through a complex network that connects the spinal cord to the brain. Partly aided by recruitment of cells of the immune system, inflammation contributes to the development of chronic pain by induces changes in this complex network of nerves such that normally harmless stimuli become horribly exaggerated (a.k.a. central sensitization). Once this occurs, painful sensations are generated within these networks in the spinal cord and brain. The proposed studies seek to identify key signaling molecules that are responsible for central sensitization of the nervous system, and to use this knowledge to develop specific therapies for chronic joint pain.