Beyond traditional therapies: a network meta-analysis on the treatment efficacy for chronic phantom limb pain

Abstract

Background: Phantom limb pain (PLP) frequently affects individuals with limb amputations. When PLP evolves into its chronic phase, known as chronic PLP, traditional therapies often fall short in providing sufficient relief. The optimal intervention for chronic PLP remains unclear.

Objective: The objectives of this network meta-analysis (NMA) were to examine the efficacy of different treatments on pain intensity for patients with chronic PLP.

Evidence review: We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and CINAHL EBSCO, focusing on randomized controlled trials (RCTs) that evaluated interventions such as neuromodulation, neural block, pharmacological methods, and alternative treatments. An NMA was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was pain score improvement, and the secondary outcomes were adverse events.

Findings: The NMA, incorporating 12 RCTs, indicated that neuromodulation, specifically repetitive transcranial magnetic stimulation, provided the most substantial pain improvement when compared with placebo/sham groups (mean difference=-2.9 points, 95% CI=-4.62 to -1.18; quality of evidence (QoE): moderate). Pharmacological intervention using morphine was associated with a significant increase in adverse event rate (OR=6.04, 95% CI=2.26 to 16.12; QoE: low).

Conclusions: The NMA suggests that neuromodulation using repetitive transcranial magnetic stimulation may be associated with significantly larger pain improvement for chronic PLP. However, the paucity of studies, varying patient characteristics across each trial, and absence of long-term results underscore the necessity for more comprehensive, large-scale RCTs.

Prospero registration number: CRD42023455949.

Keywords: CHRONIC PAIN; Nerve Block; Pharmacology; analgesia.

Figure 1. PRISMA flow diagram of studies identified and included in this network meta-analysis. CPNB, continuous perineural block; ctDCS, cerebellar transcranial direct current stimulation; EMS, electromagnetic shielding; NM (rTMS), neuromodulation with repetitive transcranial magnetic stimulation; PNS, peripheral nerve stimulation; PO (Amitriptyline), oral administration of amitriptyline; PO (Gabapentin), oral administration of gabapentin; PO (Memantine), oral administration of memantine; PO (Mexiletine), oral administration of mexiletine; PO (Morphine), oral administration of morphine; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SUCRA, surface under the cumulative ranking curve area.

Figure 2. Network geometry of different interventions for comparisons of changes in pain intensity (A) and adverse event rate (B). SUCRA value as numeric presentation of the overall ranking for all interventions (C–D). The rank would be better with larger value. Forest plots of network estimates were displayed (E–F). Number marked with asterisk indicate significance compared with sham/placebo group. L, low confidence rating; M, moderate confidence rating; SUCRA, surface under the cumulative ranking curve area.