Phantom limb pain: actual concepts of pathophysiology and therapeutic targets

Abstract

In the review, we present the main pathogenetic mechanisms of the development of phantom limb pain (PLP) after limb amputation, the prevalence of which can reach 87%. The exact mechanism of PLP remains unknown. The involvement of peripheral and central mechanisms of the formation of PLP is assumed. Peripheral mechanisms include increased excitability and the formation of ectopic activity in the amputation neuromas and in the ganglion cells of the dorsal roots of the spinal cord. The central mechanisms are represented by central sensitization in the dorsal horns of the spinal cord with the development of the “wind up” phenomenon, reorganization processes in the thalamus and cortex with thalamic and cortical remapping, and proprioceptive memory. Also significant is the neuromatrix theory, the reduction of feedback from the visual and other sensory systems after deafferentation. PLP therapy methods focused on central mechanisms are: spinal cord stimulation, transcutaneous electrical neurostimulation, deep brain stimulation, non-invasive and invasive methods of cerebral cortex stimulation, mirror therapy, virtual and augmented reality technologies, movement representation and its modification “phantom exercises”. In addition, pharmacologic treatment options based on PLP mechanisms can be used: NMDA receptor antagonists, anticonvulsants, tricyclic antidepressants, opioids.