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. The process of recalling a memory destabilizes the cellular memory trace, providing a window of opportunity for the strengthening or weakening of the memory. Similarly, we observed that the cellular 'memory' trace in the spinal cord that contributes to pathological pain sensation can also be destabilized by sensory input to the spinal cord. Through this research program, we seek to investigate the mechanisms by which ongoing sensory input can reverse the cellular changes underlying the misprocessing of painful sensory input in the spinal cord. We will identify the exact conditions of activity that enable the destabilization of the memory trace and use these findings to reverse pathological sensory processing in animal models of pain. 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.