Presynaptic mechanisms at prefrontal synapses involved in persistent pain

The cumulative evidence from animal and human studies revealed that the anterior cingulate cortex (ACC) plays essential roles in pain sensation and persistent pain. It has been evident in the ACC synapses of animals that changes in both the presynaptic and postsynaptic function are caused by peripheral nerve injury. Thus far, postsynaptic changes in the ACC following nerve injury have been primarily studied to understand the mechanisms of chronic pain. In recent years, studies focusing on the presynaptic mechanisms in chronic pain have been progressively increased. In this review, I will discuss molecular mechanisms associated with chronic pain and presynaptic form of long-term potentiation. I will also discuss evidence for presynaptic changes in the ACC caused by disease-related pain.