Can noninvasive Brain Stimulation Improve Pain and Depressive Symptoms in Patients With Neuropathic Pain? A Systematic Review and Meta-Analysis

Noninvasive brain stimulations (NIBS) have been increasingly applied to the patients with neuropathic pain (NP), while the effectiveness of NIBS in the management of NP is still conflicting.To examine the effectiveness of NIBS on pain and depression symptoms of patients with NP.A comprehensive literature retrieval was performed on MEDLINE, Embase, PsycINFO, PEDro, and CENTRAL from the establishment of the databases to June 2021. Randomized controlled trials comparing NIBS with sham stimulation were included.A total of thirteen trials comprising 498 participants met the inclusion criteria. The pooled analysis found a significant effect on the improvement of pain scores at post-treatment, favoring NIBS over sham stimulation (SMD = -0.60; 95% CI: -1.00 to -0.20; P = 0.004). Subgroup analysis showed that only transcranial direct current stimulation (tDCS) (SMD = -0.38; 95% CI: -0.71 to -0.04; P = 0.030) and high-frequency repetitive transcranial magnetic stimulation (H-rTMS) (SMD = -0.95; 95% CI: -1.85 to -0.04; P = 0.040) had positive effects on pain reduction among all types of NIBS. The favorable effects of NIBS remained significant at follow-up visit (SMD = -0.51; 95% CI: -0.79 to -0.23; P = 0.000), while only H-rTMS was found in subgroup analyses to significantly improve pain scales of the patients (SMD = -0.54; 95% CI: -0.85 to -0.24; P = 0.000). Additionally, overall NIBS showed no beneficial effect over sham stimulation in reducing depression symptoms of NP patients either at post-treatment (SMD = -0.19; 95% CI: -0.39 to 0.01; P = 0.061) or at follow-up visit (SMD = -0.18; 95% CI: -0.45 to 0.10; P = 0.202).This meta-analysis revealed the analgesic effect of NIBS on patients with NP, while no beneficial effect was observed on reducing concomitant depression symptoms. The findings recommended the clinical application of NIBS in patients with NP.