Grant: Project Grant

Pain is a key feature of arthritis, a disease of the joint and a leading cause of disability in both young and old. Despite recent advances in treating joint inflammation, and the widespread use of pain medications by arthritis patients, adequate pain control is an ongoing and challenging health care problem. Joint pain is poorly understood: some individuals with severe joint damage report little pain, while paradoxically others with seemingly minor joint damage, complain of debilitating pain. This disconnect suggests joint damage somehow influences arthritis pain, possibly by "filtering" the sensation of pain at some level in our body before reaching our brain. This proposal examines how arthritis pain impacts immune cells (microglia) in the spinal cord to mediate pain sensations between the joint and the brain. Although microglia reside within the confines of the blood brain barrier (a protective barrier that normally shields the brain), the injured joint can somehow communicate with these cells. In preliminary studies, we discovered that joint injury activates a specific molecule (the pannexin-1 channel) in microglia located in the region of the spinal cord associated with joint pain sensation. We also discovered that blocking pannexin-1 substantially reduces pain in this experimental arthritis model. Microglia, working as an amplifier at the level of the spinal cord, may influence how joint damage signals chronic pain to the brain. Understanding why and how arthritis pain occurs will enable us to develop new health care strategies to prevent or treat pain in patients with chronic joint disease.