@Article{info:doi/10.2196/63137,
author="Wang, Chenxi
and Gao, Lanqi
and Zhang, Chuan
and Li, Jun
and Liu, Jixin",
title="Neurobiological Mechanisms of Enhanced Pain-Relieving Transcutaneous Electrical Nerve Stimulation via Visuo-Tactile Stimulation in Immersive Virtual Reality: Randomized Controlled Trial",
journal="J Med Internet Res",
year="2025",
month="Mar",
day="19",
volume="27",
pages="e63137",
keywords="pain; pain-relieving; transcutaneous electrical nerve stimulation; virtual reality; electroencephalography",
abstract="Background: Enhancing the effectiveness of current pain relief strategies is a persistent clinical challenge. Although transcutaneous electrical nerve stimulation (TENS) is used in various painful conditions, its effectiveness may decline over time, requiring additional pain management strategies. Immersive virtual reality (VR) with personalized visuo-tactile stimulation has demonstrated analgesic properties. Nevertheless, whether visuo-tactile stimulation can enhance the pain-relieving outcomes of TENS and its underlying neurophysiological mechanisms remains largely unknown. Objective: The study aims to investigate whether the integration of visuo-tactile stimulation with TENS can enhance the pain-relieving outcomes of TENS alone, and we also aim to explore the brain mechanisms underlying the analgesic effect of this integrated intervention. Methods: In this study, 75 healthy participants were enrolled and randomly assigned to 1 of 3 groups: congruent TENS-VR (TENS-ConVR) and 2 control groups (incongruent TENS-VR [TENS-InVR] and TENS alone). In the context of TENS-ConVR, we combined TENS and VR by connecting TENS-induced paresthesia with personalized visual bodily feedback. The visual feedback was designed to align with the spatiotemporal patterns of the paresthesia induced by TENS. A pain rating task and a 32-channel electroencephalography were applied. Results: Two-way ANOVAs showed that TENS-ConVR exhibited a statistically greater reduction in pain rating (F1,48=6.84; P=.01) and N2 amplitude (F1,48=5.69; P=.02) to high-intensity pain stimuli before and after stimulation than TENS alone. The reduction of brain activity was stronger in participants who reported stronger pain-relieving outcomes. TENS-ConVR reduced the brain oscillation in the gamma band, whereas this result was not found in TENS alone. Conclusions: This study observed that combining TENS and visual stimulation in a single solution could enhance the pain-relieving effect of TENS, which has the potential to improve the effectiveness of current pain management treatments. Trial Registration: Chinese Clinical Trial Registry ChiCTR2500098834; https://www.chictr.org.cn/showprojEN.html?proj=254171 ",
issn="1438-8871",
doi="10.2196/63137",
url="https://www.jmir.org/2025/1/e63137",
url="https://doi.org/10.2196/63137"
}