Effective pain management remains a major clinical challenge. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising, non-invasive neuromodulation technique due to its safety, ease of administration, and cost-effectiveness. Preliminary evidence suggests that taVNS exerts analgesic effects by activating afferent vagal fibers, which integrate signals in key central nodes such as the nucleus tractus solitarius (NTS). This process subsequently modulates pain-processing networks, neurotransmitter balance, inflammatory responses, and autonomic function. Despite its potential, the precise central neural mechanisms underlying taVNS-induced analgesia remain unclear, limiting the optimization of stimulation parameters (e.g., intensity, frequency, and target specificity) and the enhancement of long-term therapeutic outcomes. Previous studies have highlighted the role of taVNS in activating descending pain inhibitory pathways and modulating the limbic system, yet a comprehensive understanding of the causal neurophysiological dynamics is still lacking. This study aims to investigate the analgesic efficacy of taVNS using a capsaicin-induced pain model. Furthermore, by employing Transcranial Magnetic Stimulation combined with Electroencephalography (TMS-EEG), we seek to elucidate the central neural mechanisms of taVNS. By integrating causal intervention with high-temporal resolution brain activity recording, this research will provide scientific insights into the modulation of pain-related pathways-such as descending inhibitory and cognitive-affective networks-ultimately facilitating the development of standardized, individualized, and precise clinical interventions for pain management.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
30
Participants receive taVNS using a percutaneous electrical stimulation device. The stimulation is delivered to the auricular branch of the vagus nerve via two modified punctate electrodes with the following parameters: frequency = 30 Hz, pulse width = 200 μs, duration = 30 minutes.
Participants receive sham stimulation via the same device, with parameters set to 0.1 Hz for 30 minutes, designed to provide minimal sensory input that is indistinguishable from the active stimulation to ensure double-blinding.
Pain Intensity
Measured using the Visual Analog Scale (VAS).
Time frame: Baseline and every 10 minutes up to 90 minutes post-capsaicin application.
Neural Plasticity and Brain Activity
Assessed via TMS-EEG (Transcranial Magnetic Stimulation combined with Electroencephalography), including TMS-Evoked Potentials (TEPs) (e.g., N40, P60, N100, P200), neural oscillations, and global field power.
Time frame: Baseline (pre-intervention), 40 minutes, and 90 minutes post-capsaicin application.
Brain Network Connectivity
Assessed via weighted phase lag index (wPLI) based on EEG data to evaluate whole-brain network connectivity changes.
Time frame: Baseline (pre-intervention), 40 minutes, and 90 minutes post-capsaicin application.
Pain-Related Emotional States
Assessed using a standardized pain-related emotional scale to evaluate changes in emotional state following the intervention.
Time frame: From baseline through 90 minutes post-capsaicin application, assessed every 10 minutes.
Pain-Related Cognitive States
Assessed using a standardized pain-related cognitive scale to evaluate changes in cognitive processing following the intervention.
Time frame: At baseline, 40 minutes post-capsaicin, and 90 minutes post-capsaicin.
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