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Helena Knotkova1,2, Ricardo Cruciani1–3, Volker M Tronnier4, Dirk Rasche41Department of Pain Medicine and Palliative Care, Research Division, Institute for Non-invasive Brain Stimulation, Beth Israel Medical Center, New York, NY, USA; 2Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA; 3Department of Anesthesiology, Albert Einstein College of Medicine, Bronx, NY, USA; 4Department of Neurosurgery, University of Lübeck, GermanyAbstract: Phantom-limb pain (PLP) belongs among difficult-to-treat chronic pain syndromes. Treatment options for PLP are to a large degree implicated by the level of understanding the mechanisms and nature of PLP. Research and clinical findings acknowledge the neuropathic nature of PLP and also suggest that both peripheral as well as central mechanisms, including neuroplastic changes in central nervous system, can contribute to PLP. Neuroimaging studies in PLP have indicated a relation between PLP and the neuroplastic changes. Further, it has been shown that the pathological neuroplastic changes could be reverted, and there is a parallel between an improvement (reversal) of the neuroplastic changes in PLP and pain relief. These findings facilitated explorations of novel neuromodulatory treatment strategies, adding to the variety of treatment approaches in PLP. Overall, available treatment options in PLP include pharmacological treatment, supportive non-pharmacological non-invasive strategies (eg, neuromodulation using transcranial magnetic stimulation, visual feedback therapy, or motor imagery; peripheral transcutaneous electrical nerve stimulation, physical therapy, reflexology, or various psychotherapeutic approaches), and invasive treatment strategies (eg, surgical destructive procedures, nerve blocks, or invasive neuromodulation using deep brain stimulation, motor cortex stimulation, or spinal cord stimulation). Venues of further development in PLP management include a technological and methodological improvement of existing treatment methods, an implementation of new techniques and products, and a development of new treatment approaches.Keywords: phantom-limb pain (PLP), neuropathic pain, non-invasive treatment, invasive treatment, neuromodulation