Maladaptive plasticity, memory for pain and phantom limb pain: review and suggestions for new therapies.

A number of studies have shown that phantom limb pain is associated with plastic changes along the neuraxis, with a close correlation between changes in the cortical representation of the affected limb and phantom limb pain. Mechanisms underlying these maladaptive plastic changes are related to a loss of GABAergic inhibition, glutamate-mediated long-term potentiation-like changes and structural alterations such as axonal sprouting. These plastic changes and phantom limb pain seem to be more extensive when chronic pain precedes the amputation. Behavioral interventions, stimulation, feedback and pharmacological interventions that are designed to reverse these maladaptive memory traces and enhance extinction may be beneficial for the treatment and prevention of phantom limb pain.