Evidence-based clinical practice guideline for the prevention and management of phantom limb pain in patients undergoing amputation: a proposal

Abstract

Phantom limb pain (PLP) is a common and distressing complication that occurs after limb amputation in a large proportion of amputees. Despite advancements in surgical and anesthetic techniques, current medical approaches have not established a universally effective strategy for preventing or controlling PLP. A multidisciplinary approach, together with early identification of risk factors, is essential to reduce both the incidence and severity of PLP. We aimed to propose an evidence-based clinical practice guideline for the prevention and management of phantom limb pain among patients undergoing amputation surgery. A comprehensive literature review was conducted, including systematic reviews, randomized controlled trials, meta-analyses, and high-quality cohort studies published between 2015 and 2025. Evidence was graded using the Oxford Centre for Evidence-Based Medicine (CEBM) Levels of Evidence, and the Grade of Recommendation (GOR) was assigned accordingly. When high-level evidence was limited, expert consensus was incorporated into the recommendation process. A total of 24 studies were included in the proposed guideline development. High-level evidence supports non-pharmacologic interventions, particularly the combination of mirror therapy, phantom exercises, and graded motor imagery (LOE 1a, GOR A). Preoperative gabapentin combined with intraoperative regional anesthesia was effective in reducing the occurrence of PLP. Surgical techniques such as targeted muscle reinnervation (TMR) and cryoneurolysis demonstrated beneficial effects in prevention and management. Peripheral nerve blocks and epidural analgesia were identified as optimal strategies for perioperative pain control. Neuromodulation, memantine, and calcitonin may be considered for acute or refractory PLP, whereas opioids should be reserved as last-line options due to safety concerns. Effective management of PLP requires proactive prevention strategies integrating preoperative psychological support, pharmacologic prophylaxis, regional anesthesia techniques, and selected surgical interventions. Implementation of these evidence-based recommendations may reduce the burden and improve outcomes for patients undergoing amputation.