Transcutaneous Electric Nerve Stimulation in Animal Model Studies: From Neural Mechanisms to Biological Effects for Analgesia

Objective: This systematic and meta-analysis review evaluated the transcutaneous electrical nerve stimulation (TENS)-induced action mechanisms for animal analgesia. Materials and Methods: Two independent investigators identified relevant articles published until February 2021 through a literature review, and a random-effects meta-analysis was performed to synthesize the results. Results: Of the 6984 studies found in the data base search, 53 full-text articles were selected and used in the systematic review. Most studies used Sprague Dawley rats (66.03%). High-frequency TENS was applied to at least one group in 47 studies, and most applications were performed for 20 minutes (64.15%). Mechanical hyperalgesia was analyzed as the primary outcome in 52.83% of the studies and thermal hyperalgesia in 23.07% of studies using a heated surface. More than 50% of the studies showed a low risk of bias on allocation concealment, random housing, selective outcome reporting, and acclimatization before the behavioral tests. Blinding was not performed in only one study and random outcome assessment in another study; acclimatization before the behavioral tests was not performed in just one study. Many studies had an uncertain risk of bias. Meta-analyses indicated no difference between low-frequency and high-frequency TENS with variations among the pain models. Conclusions: This systematic review and meta-analysis suggests that TENS has presented a substantial scientific foundation for its hypoalgesic effect in preclinical studies for analgesia.