Functional and structural brain changes in patients with phantom limb pain

Phantom limb is a sensation of a missing hand that patients feel after amputation, and phantom limb pain or phantom pain is a pain in a phantom limb. Phantom limb pain occurs in 45 % – 85 % of amputees, and a part of them becomes refractory. Thus, it is needed to fully understand the pathophysiology of phantom limb pain for the devel-opment of effective treatments. To elucidate the central mechanisms of phantom limb pain, functional and anatomical changes in the brain has been explored by using non– invasive brain activity recording technique such as electroencephalography (EEG), magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). In 1995 , Flor and colleagues reported that the somatotopic organization of the primary somatosensory cortex had altered in patients with phantom limb pain and the magnitude of this alteration had been associated with the intensity of their phantom limb pain. Based on these results, they proposed a model that alterations in the somatotopic organization of a missing hand are involved in phantom limb pain. Now, this model is known as the maladaptive reorganization model. Over the following 20 years, a variety of supporting evidence has been provided, and this model has been widely accepted. However, Makin and colleagues provided evidence against this model in 2013 . They demonstrated that cortical representation of a missing hand had been preserved and activation evoked by phantom limb movement had been related to the severity of phantom limb pain. After that, the maladaptive reorganization model has been revisited, and recent studies have suggested that functional alterations in the primary motor cortex rather than the primary sensory cortex are associated with phantom limb pain. Most recently, by using brain–machine interface technology, Yanagisawa and colleagues demonstrated that the activity of the missing hand area in the sensorimotor cortex is closely related to phantom limb pain. However, detailed neural mechanisms of phantom limb pain remain unclear so far, although many changes in the peripheral