Electrical Nerve Stimulation Induces Synaptic Plasticity in the Brain and the Spinal Cord: A Systematic Review

Objectives This review aimed to compile the literature on synaptic plasticity induced by electrical nerve stimulation (ENS) in nociceptive and somatosensory circuits within the central nervous system, with a particular focus on its effects on both the brain and spinal cord. Understanding the mechanisms underlying synaptic changes, enhances our comprehension of how ENS contributes to both pain relief and the development of experimental pain models. Materials and Methods We conducted a systematic search of PubMed, Scopus, PEDro, SciELO, and Cochrane databases, adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and evaluated the quality of evidence using SYRCLE’s risk of bias tool. The inclusion criteria were application of ENS to peripheral nerves, reporting of a detailed methodology, providing direct physiological measurements of synaptic activity (eg, field potentials or intracellular recordings), and publication in English or Spanish. From 8094 results, 85 studies met the inclusion criteria. Results ENS was found to induce synaptic potentiation in 70 studies, depression in 7, and both effects in 8. These outcomes were determined by specific stimulation parameters and individual characteristics, with distinct molecular mechanisms involved in each case. Notably, most research focused on long-term potentiation in nociceptive pathways to create experimental pain models, with most studies conducted in the spinal cord. Few studies explored the link between ENS-induced synaptic plasticity and its analgesic effects or the role of plasticity in supraspinal brain regions, suggesting promising areas for future research. Conclusions ENS-induced synaptic plasticity presents a valuable opportunity for both pain management and the development of experimental pain models. Further research is needed to explore the connections between plasticity, analgesia, and higher brain regions.