Non-Invasive Neuromodulation for Pain Management in Children and Adolescents: A Systematic Review of Randomized Controlled Trials

Pain in children and adolescents remains an underestimated and undertreated condition, with long-term physical and psychosocial consequences. Non-invasive neuromodulation has emerged as a promising, low-risk approach for managing acute and chronic pain by modulating central and peripheral neural pathways. This systematic review followed PRISMA 2020 guidelines to evaluate the efficacy, safety, and clinical applicability of non-invasive neuromodulation techniques in pediatric pain. Searches were conducted in PubMed, Embase, Scopus, Web of Science, Cochrane CENTRAL, and ScienceDirect for randomized controlled trials (RCTs) published between 2015 and 2025. Six RCTs met the inclusion criteria, encompassing percutaneous electrical nerve field stimulation (PENFS), transcutaneous auricular vagus nerve stimulation (taVNS), transcutaneous electrical acupoint stimulation (TEAS), and transcutaneous electrical nerve stimulation (TENS). Four trials reported significant reductions in pain intensity alongside improvements in functional outcomes and quality of life, particularly in functional abdominal pain and postoperative contexts. Most studies showed low or moderate risk across domains, with appropriate randomization and blinded assessment. No serious adverse events were reported, confirming an excellent safety profile. These findings support non-invasive neuromodulation as a feasible and well-tolerated adjunct to conventional pediatric pain management. Further high-quality trials are warranted to standardize protocols and explore mechanisms of neuroplasticity in the developing nervous system. PROSPERO (CRD420251170866).