Non-invasive neuromodulation for neuropathic pain: an evidence-informed clinical roadmap proposal
TL;DR
An evidence-informed clinical roadmap to support decision-making for non-invasive neuromodulation in NeP is developed and refinement of the treatment sequence and removal of transcutaneous auricular vagus nerve stimulation is removed from the roadmap.
Abstract
Background
Non-invasive neuromodulation has shown analgesic effects in neuropathic pain (NeP) but translating the available evidence into practical decisions regarding technique, target, and stimulation protocol remains challenging.
Objective
To develop an evidence-informed clinical roadmap to support decision-making for non-invasive neuromodulation in NeP and refine it through multidisciplinary expert appraisal.
Methods
PubMed was searched up to July 9, 2025, for systematic reviews with meta-analyses published from 2015 onward. Two reviewers independently screened eligible studies, with disagreements resolved by consensus with a third reviewer when necessary. Meta-analyses were qualitatively appraised considering recency, statistical significance, heterogeneity, and consistency of findings. Trials with the largest effect sizes and relative weight in the selected meta-analyses were examined, and stimulation protocols from methodologically adequate studies were extracted and assessed using the PEDro scale. The resulting roadmap was appraised by six experts in pain and neuromodulation.
Results
Seven meta-analyses and eight randomized clinical trials were included. High-frequency rTMS and anodal tDCS showed short-term analgesic effects across several NeP conditions. Expert appraisal focused on clarity, clinical logic, applicability, and feasibility, resulting in refinement of the treatment sequence and removal of transcutaneous auricular vagus nerve stimulation (taVNS) from the roadmap.
Conclusions
The proposed evidence-informed roadmap integrates findings from meta-analyses and randomized trials with multidisciplinary expert appraisal to support clinical decision-making in NeP. Prospective studies are needed to evaluate its clinical utility.