Wind-up pain is caused by a series of events in synapses and in nerve cells. NMDA receptors are activated when Substance P attaches to NK-1 receptors and then incorporated into the cell, activating Protein Kinase-C. This then removes the magnesium blocking the actuation of the NMDA receptor. Glutamate attaches to internal receptor sites in the NMDA receptor and Calcium floods into the cell, causing the pain signal to increase and fire more frequently.
