Effects and Mechanisms of Temporal Interference Stimulation (TIS) on Neuropathic Pain (TIS)

Experimental: tTIS group

Following enrollment, patients underwent TIS treatment administered twice daily over five consecutive days, for a total of ten sessions. The stimulation was targeted at the periaqueductal gray (PAG) region contralateral to the side of pain. Assessments were conducted before treatment (T0) and immediately after the treatment course (T1), evaluating pain perception, emotional changes, and quality of life. Additionally, local and whole-brain mechanisms were examined using TIS-EEG and fMRI.

Dispositivo: Transcranial temporal interference stimulation

tTIS was applied to the PAG contralateral to the pain side for a duration of 20 minutes, comprising a 30-second ramp-up phase and a 30-second ramp-down phase.

Otros nombres:

• ttis

Comparador falso: Sham group

The sham group followed the same procedure as the TIS group. However, the electrical current was only delivered in a 30-second ramp-up at the beginning and a 30-second ramp-down at the end of each session to replicate the initial peripheral sensation without providing sustained therapeutic stimulation.

Dispositivo: Transcranial temporal interference stimulation

tTIS was applied to the PAG contralateral to the pain side for a duration of 20 minutes, comprising a 30-second ramp-up phase and a 30-second ramp-down phase.

Otros nombres:

• ttis

visual analogue scale(VAS)

It typically consists of a 10-centimeter straight line, with two endpoints representing extreme states of the measured experience. For example, when assessing pain, one end is labeled "0 (no pain at all)" and the other end "10 (worst pain imaginable, unbearable)".

short-form McGill Pain Questionnaire (SF-MPQ)

The Pain Rating Index of the Short-Form McGill Pain Questionnaire consists of 15 pain descriptors, including 11 sensory descriptors and 4 affective descriptors. Each item is rated from 0 (none) to 3 (severe). Item scores are summed to produce a total score ranging from 0 to 45, with higher scores indicating greater pain severity. The outcome measure is the change in the total Pain Rating Index score from baseline to Day 5 after intervention.

Brief Pain Inventory (BPI)

0 = "does not interfere" to 10 = "interferes completely" based on the past 24 hours.

The Patient Global Impression of Change (PGIC)

Single-item structure: It consists of a single question that asks patients to rate how much their condition has changed since a specified baseline.2.7-point response scale: Responses range from "very much improved" (score 1) to "very much worse" (score 7), with intermediate options including "much improved," "minimally improved," "no change," "minimally worse," and "much worse."

17-items of Hamilton Depression Rating Scale (HAMD)

The HAMD-17 provides a comprehensive, multi-dimensional snapshot of depression severity, heavily emphasizing sleep, physical (somatic), and anxiety symptoms alongside core mood symptoms

The Beck Depression Inventory-II (BDI-II)

BDI-II is a widely used self-report questionnaire designed to assess the severity of depressive symptoms in adults and adolescents.It consists of 21 items, each describing a specific depressive symptom (e.g., sadness, loss of interest, guilt, fatigue, sleep disturbances, appetite changes).

TIS-EEG: Mean Change From Baseline in Resting-State Posterior Alpha-Band Relative Power at Day 5

A 5-minute eyes-closed resting-state electroencephalography recording will be obtained before the first intervention and after the final intervention.

Mean Within-Session Change in Alpha-Band Relative Power During Transcranial Temporal Interference Stimulation on Day 5

Electroencephalography will be continuously recorded during the 20-minute transcranial temporal interference stimulation session. After removal of stimulation-related and physiological artifacts using a prespecified preprocessing procedure, alpha-band relative power will be calculated within the 8-13 Hz frequency range and averaged across all included electroencephalography electrodes. Relative alpha power will be calculated as alpha-band power divided by total power within the 1-45 Hz frequency range and multiplied by 100. The within-session change will be calculated as the mean relative alpha power during the final 5 minutes of stimulation minus the mean relative alpha power during the first 5 minutes of stimulation and reported in percentage points.