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Objectives Repetitive transcranial magnetic stimulation (rTMS) is a promising tool for treatment of chronic pain. We describe the use of navigated rTMS to treat a patient affected by phantom limb pain (PLP) and to modulate brain functional connectivity. We reviewed the literature on the use of rTMS as a tool for relieving central pain by promoting brain plasticity. Methods A 69-year-old patient came to our observation blaming severe pain (Visual Analog scale, VAS, score 9) to a phantom right lower limb. We mapped left primary motor area (PMA) by navigated TMS and assessed connectivity with resting-state functional MR (rsfMR). The patient underwent 30-days navigated rTMS treatment. We applied low-frequency stimulation (1 Hz) over the primary somatosensory area (PSA) and high-frequency stimulation (10 Hz) over PMA and dorsolateral prefrontal cortex (DLPFC) of the left hemisphere. Results This strategy allowed a pain relief with a reduction of 5 points of the VAS score after 1 month. Post-treatment rsfMR showed increased connectivity, mainly in the sensory-motor network and the unaffected hemisphere (P < 0.05). Discussion This report represents a proof-of-concept that navigated rTMS can be effectively used to stimulate selected brain areas in PLP patients in order to promote brain connectivity, and that rsfMR is a useful tool able to analyze functional results. In the literature, we found data supporting the assumption that, in patients affected by PLP, a reduced connectivity in interhemispherical and sensory-motor network plays a role in generating pain and that rTMS has the potential to restore impaired connectivity.

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