Tieyi Shi, Ziling Deng, Ming Ma, Quanbo Li, Yan Wang
Several neuromodulation interventions were associated with greater pain reduction than their available control conditions. However, most comparisons between active interventions were not statistically significant, the evidence network was uneven, and confidence in the evidence was very low. Treatment rankings should therefore be considered exploratory and should not be interpreted as establishing the superiority of any individual intervention.
BACKGROUND: Neuromodulation is increasingly used for chronic neuropathic pain, but the comparative efficacy of invasive and non-invasive techniques remains unclear. This systematic review and network meta-analysis compared different neuromodulation interventions for chronic central and peripheral neuropathic pain.
METHODS: Randomized controlled trials were searched in PubMed, Embase, CENTRAL, Web of Science, and trial registries from inception to March 6, 2026. Eligible interventions included repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcutaneous electrical nerve stimulation (TENS), spinal cord stimulation (SCS), peripheral nerve stimulation (PNS), and dorsal root ganglion stimulation (DRG-S). The primary outcome was pain intensity at the primary endpoint reported in each study. Random-effects network meta-analysis was performed, and treatment ranking was assessed using surface under the cumulative ranking curve (SUCRA) values. Risk of bias and confidence in the evidence were evaluated using Risk of Bias 2 (RoB 2) and Confidence in Network Meta-Analysis (CINeMA), respectively.
RESULTS: A total of 68 randomized controlled trials were included in the systematic review and meta-analysis. Most active neuromodulation interventions showed greater pain reduction than control conditions. PNS was significantly superior to sham stimulation, no treatment, and conventional medical management, while SCS was significantly superior to no treatment and conventional medical management. rTMS, TENS, and tDCS also significantly reduced pain compared with sham stimulation. PNS, SCS, and rTMS occupied relatively high ranking positions; however, these rankings were derived from a heterogeneous and uneven evidence network with very low confidence and should not be interpreted as evidence of treatment superiority.
CONCLUSION: Several neuromodulation interventions were associated with greater pain reduction than their available control conditions. However, most comparisons between active interventions were not statistically significant, the evidence network was uneven, and confidence in the evidence was very low. Treatment rankings should therefore be considered exploratory and should not be interpreted as establishing the superiority of any individual intervention.