Grant: Project Grant

Intractable, pathological pain is the single most common cause of disability, affecting more than 20% of the population world-wide. Enhanced or abnormal pain sensations that typify chronic pain can arise from cellular changes in sensory processing pathways in the spinal cord. In our previous work, we've observed that the cellular changes that occur during the development of persistent pain in the spinal cord are strikingly similar to the changes that occur in the brain during memory formation. Specifically, we have drawn a parallel between the cellular processes in the brain that allow memories to be updated or strengthened, and the processes that are initiated by ongoing activation of pain-sensitive cells in the spinal cord. Through this research program, we seek to investigate the mechanisms by which ongoing sensory input can destabilize the cellular changes underlying the misprocessing of sensory input in the spinal cord. We will identify how ongoing pain input can lead contributes to the destabilization of the pain memory trace and lead to recovery of pathological pain. We will further identify unique molecular conditions in chronic pain that prevent pain recovery through this phenomenon, and identify new ways to bypass these changes and promote pain recovery. These data will reveal new approaches for the reversal of pathological pain and provide detailed insight into the role of aberrant spinal activity in various causes of pathological pain.