Transcranial magnetic stimulation in subjects with phantom pain and non-painful phantom sensations: a systematic review

Several studies have applied transcranial magnetic stimulation (TMS) in the attempt to further explore the pathophysiological mechanisms of phantom-limb pain (PLP) and non-painful phantom sensations (PS). We performed a systematic review of available evidence of this emerging technology in this indication. We identified studies which report a reduced intracortical inhibition and increased intracortical facilitation in the hemisphere contralateral to the PLP. TMS mapping revealed a significant lateralization of the center of gravity and an enlargement of the excitable area on the hemisphere contralateral to the amputation. N-Methyl-D-Aspartate-mediated mechanisms influence the changes of intracortical inhibition and facilitation occurring after limb amputation; however, these cortical excitability changes and PLP are independent of each other. TMS can also influence brain function if applied repetitively. A few studies have begun to therapeutically use repetitive TMS (rTMS) to relief PLP and non-painful PS. rTMS of the contralateral parietal cortex lead to a transient reduction in pain intensity. High frequency rTMS applied over the contralateral motor cortex (M1) or low frequency rTMS over the unaffected hemisphere might also induce significant clinical improvement in PLP. On the other hand, serum beta-endorphin increased significantly after real stimulation over contralateral M1. This systematic review illustrates that TMS technique is an emerging tool to gain insights to pathophysiological aspects of pain and non-painful phantom phenomena. Moreover, TMS could support appropriate patient selection for different therapies and may also have therapeutic utility in subjects with PLP or PS, though the evidence is still very preliminary and well-designed studies in larger cohort of patients are warranted.