Neuromodulation therapy for phantom limb pain: A review of the current status and future perspectives

Phantom Limb Pain (PLP) is a common and intractable neuropathic pain condition that occurs following limb amputation, significantly impacting patients’ quality of life. The prevalence of PLP ranges from 45% to 85%. Traditional pharmacological treatments have limited efficacy and are frequently accompanied by significant side effects. This review aims to provide a comprehensive overview of the multi-level pathophysiological mechanisms underlying PLP, synthesize clinical evidence on both invasive and non-invasive neuromodulation techniques, analyze differences in therapeutic outcomes and targets, and offer insights for clinical practice and future research. This is a narrative review that integrates the existing evidence and current clinical applications of various treatment approaches for PLP. The mechanisms of PLP involve peripheral nerve ectopic discharges, cortical reorganization, and the interaction of various psychological factors. The short-term efficacy of invasive treatments, such as spinal cord stimulation (SCS) and dorsal root ganglion (DRG) stimulation, ranges from 14% to 80%. DRG stimulation shows more promise in terms of long-term stability. Non-invasive techniques, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), when combined with mirror therapy, can enhance therapeutic outcomes. Emerging technologies, such as brain-computer interfaces (BCI) and temporally interfering stimulation (TIS), remain in the preclinical phase of investigation. Neuromodulation techniques offer a multi-dimensional treatment strategy for PLP, with potential improvements through parameter standardization, individualized treatment optimization, validation in multi-center randomized controlled trials, and an overall enhancement of clinical efficacy. • This review provides a comprehensive overview of recent applications and advances of neuromodulation for phantom limb pain. • We systematically evaluate the merits and drawbacks of both invasive and non‑invasive neuromodulation therapies for phantom limb pain. • We highlight the potential of emerging neuromodulation strategies (BCI, TI stimulation, tPBM, tFUS) for PLP management.