Fig. 1.

A model for enhanced excitatory synaptic transmission in the pain-related ACC after amputation. Under normal physiological conditions, acute sensory experience may trigger short-lasting plastic changes in the ACC synapses. LTD provides an important mechanism to 'reset' those enhanced synapses. Thus, the cortical synapses and circuits are maintained at baseline levels, and allowed to process multiple sensory experiences. In case of amputation, abnormal neuronal activity from the periphery triggers long-lasting changes in cortical synapses, these may include changes at transcriptional and translational levels. Consequently, ACC synapses loss the ability to undergo LTD, or failure to reset the enhanced synapses. Enhanced cortical synapses may direct contribute to pain perception without additional sensory inputs or with the help of baseline brain activity (or noise brain activity) (or called central pain in some cases). It may also contribute to phantom limb sensations, as well as hyperalgesia or allodynia when the same synapses also receive peripheral noxious or non-noxious inputs. Resetting these enhanced synapses or recover the ability to undergo LTD may help us to control or reduce phantom pain.