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

This study employs temporal interference stimulation (tTIS) to investigate the analgesic effects of tTIS on neuropathic pain and monitor changes in neural plasticity, and explore the dynamic relationship between analgesic efficacy and neural plasticity, thereby providing new strategies for the treatment of neuropathic pain.

Study Overview

• Status: Not yet recruiting
• Conditions: Neuropathic Pain; tTIS
• Intervention / Treatment: Device: Transcranial temporal interference stimulation

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• IASP diagnosis of peripheral neuropathic pain;
• At least one month after the onset of pain;
• At least moderate pain intensity (≥ 3 assessed by VAS or NRS);
• 18 years or older;
• Stable medical treatment from 2 weeks before allocation to the end of the trial;
• Willing to receive TIS treatment and capable of fulfilling clinical assessments.

Exclusion Criteria:

• Contradictions to TIS treatment, such as metal implants or seizure;
• Serious psychiatric disorder (Hamilton Depression Rating Scale score ≥ 35 or Hamilton Anxiety Rating Scale score ≥ 29);
• Aphasia or cognitive disorders (Mini mental state examination ≤ 24);
• Severe clinical disorders caused by tumor or other conditions;
• Severe cardiopulmonary dysfunction or extreme weakness;
• History of substance abuse (alcohol, drugs).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Device: 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.; Other Names: tTIS
Sham Comparator: 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.	Device: 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.; Other Names: tTIS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)".	Day1(Baseline), day 5 after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day1(Baseline), day 5 after intervention
Brief Pain Inventory (BPI)	0 = "does not interfere" to 10 = "interferes completely" based on the past 24 hours.	Day1(Baseline), day 5 after intervention
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."	Day1(Baseline), day 5 after intervention
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	Day1(Baseline), day 5 after intervention
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).	Day1(Baseline), day 5 after intervention
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.	Day 1 before the first intervention and Day 5 within 30 minutes after completion of 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.	During the 20-minute transcranial temporal interference stimulation session on Day 5

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: July 29, 2026
• First Posted (Actual): July 30, 2026

Study Record Updates

• Last Update Posted (Actual): July 30, 2026
• Last Update Submitted That Met QC Criteria: July 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neuralgia
• Other Study ID Numbers: 2025-1132

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No