Steve Lacroix, University Laval, Quebec, Canada

Interleukin-1 alpha mediates secondary degeneration and neuropathic pain after spinal cord injury

Funded in: 2020, 2021, 2022


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Problem: Interleukin-1 alpha triggers the death of oligodendrocytes and may also activate nociceptors
Target: Identify the pathways by which the danger signal IL-1 alpha mediates secondary degeneration and chronic pain
Goal: Successful strategies for manipulating immune cells and inflammation in order to reduce functional deficits and chronic pain

A major consequence of spinal cord injury is the loss of neural tissue at the site of lesion. This results in an inflammatory response characterized by the infiltration of blood-derived immune cells that are essential to the clearance of cellular debris. However, some of the molecules released by immune cells also contribute to secondary damage, causing the death of neural cells (termed neurons) and cells that are producing the coating of nerve fibers (termed oligodendrocytes). Importantly, recent work from the Lacroix laboratory has established that inflammatory molecules can also stimulate pain receptors (termed nociceptors), resulting in chronic pain.
Among the factors that mediate inflammation are molecules normally found within resident cells of the spinal cord, but that are released when the cells are injured. These intracellular host molecules, called danger signals, include the inflammatory protein interleukin (IL)-1 alpha. Under normal conditions, IL-1 alpha is sequestrated inside microglia, a resident population of immune cells in the spinal cord. However, when released after cell damage, IL-1 alpha becomes a powerful activator of inflammation. The Lacroix laboratory recently discovered that in addition to its role in inflammation, IL-1 alpha triggers the death of oligodendrocytes and may also activate nociceptors. The main goal of this research project is to identify the mechanisms involved in these responses and to utilize this knowledge to prevent secondary damage and chronic pain after spinal cord injury.
These studies should therefore help define successful strategies for manipulating immune cells and inflammation in order to reduce functional deficits and chronic pain after spinal cord injury.