Cortical depression and potentiation: basic mechanisms for phantom pain

Abstract

People experience the feeling of the missing body part long after it has been removed after amputation are known as phantom limb sensations. These sensations can be painful, sometimes becoming chronic and lasting for several years (or called phantom pain). Medical treatment for these individuals is limited. Recent neurobiological investigations of brain plasticity after amputation have revealed new insights into the changes in the brain that may cause phantom limb sensations and phantom pain. In this article, I review recent progresses of the cortical plasticity in the anterior cingulate cortex (ACC), a critical cortical area for pain sensation, and explore how they are related to abnormal sensory sensations such as phantom pain. An understanding of these alterations may guide future research into medical treatment for these disorders.

Keywords: amputation; anterior cingulate cortex; long-term depression; long-term potentiation; mice; phantom pain.

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.