Analgesia, Capsaicin-Induced Pain, Electroencephalography, Neuromodulation, Pain Management, Transcranial Magnetic Stimulation Repetitive, Vagus Nerve Stimulation
Conditions
Brief summary
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.
Interventions
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.
Sponsors
Study design
Eligibility
Inclusion criteria
\- 1. Adults aged 18 to 65 years. 2. Physically and mentally healthy individuals with no history of chronic pain (confirmed via clinical interviews and the MINI International Neuropsychiatric Interview). 3\. Right-handed.
Exclusion criteria
* 1\. Presence of metallic implants (e.g., cardiac pacemakers) or other conditions precluding vagus nerve stimulation. 2\. Diagnosis of psychiatric disorders or presence of suicidal ideation. 3. History of epilepsy. 4. History of drug or substance abuse/dependence. 5. Known allergy to capsaicin or its vehicle solutions. 6. Inability to understand or respond to study-related questions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity | Baseline and every 10 minutes up to 90 minutes post-capsaicin application. | Measured using the Visual Analog Scale (VAS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neural Plasticity and Brain Activity | Baseline (pre-intervention), 40 minutes, and 90 minutes post-capsaicin application. | 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. |
| Brain Network Connectivity | Baseline (pre-intervention), 40 minutes, and 90 minutes post-capsaicin application. | Assessed via weighted phase lag index (wPLI) based on EEG data to evaluate whole-brain network connectivity changes. |
| Pain-Related Emotional States | From baseline through 90 minutes post-capsaicin application, assessed every 10 minutes. | Assessed using a standardized pain-related emotional scale to evaluate changes in emotional state following the intervention. |
| Pain-Related Cognitive States | At baseline, 40 minutes post-capsaicin, and 90 minutes post-capsaicin. | Assessed using a standardized pain-related cognitive scale to evaluate changes in cognitive processing following the intervention. |