Origin of phantom limb pain: A dynamic network perspective

Abstract

Functional and structural plasticity in neural circuits may actively contribute to chronic pain. Changes in the central nervous system following limb amputation are one of the most remarkable evidences of brain plasticity. Such plastic changes result from combined sensorimotor deprivation with intense behavioral changes, including both acquisition of compensatory motor skills and coping with a chronic pain condition (phantom limb pain), which is a common consequence after amputation. This review aims to discuss the latest insights on functional changes and reorganization in nociceptive pathways, integrating analyses in human patients across several scales. Importantly, we address how functional changes interrelate with pain symptoms, not only locally within the primary somatosensory cortex but at a network-level including both spinal and cerebral areas of the nociceptive and pain networks. In addition, changes in the function of neurons and neural networks related to altered peripheral input are dynamic and influenced by psychological factors such as learning, prosthesis usage or frequency of use of the intact limb as well as comorbidity with anxiety and depression. We propose that both central and peripheral factors interact in a dynamic manner and create the phantom pain experience.