Analysis of the Analgesic Mechanism of TENS-WAA During Non-anesthetized Colonoscopy Using EEG-fNIRS System

Analysis of the Analgesic Mechanism of Transcutaneous Electrical Nerve Stimulation Based on Wrist-ankle Acupuncture Theory During Non-anesthetized Colonoscopy Using Electroencephalogram-Functional Infrared Spectroscopy System

This study is a single-center, randomized controlled trial aiming to evaluate the analgesic mechanism of Transcutaneous Electrical Nerve Stimulation based on Wrist-Ankle Acupuncture (TENS-WAA) during unsedated colonoscopy using EEG-fNIRS technology to assess neural activity in brain regions associated with pain perception. Sixty patients aged 18-75 years, with stable cardiopulmonary function and a baseline visual analog scale (VAS) pain score <3, will be enrolled and randomly allocated into the intervention and control groups. The intervention group will receive TENS stimulation based on the Wrist-Ankle Acupuncture theory 10 minutes before the colonoscopy, with a frequency of 2 Hz and adjustable current intensity ranging from 1 to 9 mA. The control group will receive minimal-intensity sham stimulation under identical conditions. All participants will wear EEG-fNIRS devices to monitor neural activity in key pain-related brain areas, including the prefrontal cortex, anterior cingulate cortex, motor cortex, and parietal cortex. Primary outcomes include EEG-fNIRS data, while secondary outcomes are VAS scores at the four colonic bends, colonoscopy duration, and the correlation between EEG-fNIRS signals and pain perception. Statistical analyses will include multivariable linear regression, generalized estimating equations, and mixed-effects models to investigate the analgesic effects and neural mechanisms of TENS-WAA. This study seeks to provide innovative pain management strategies for patients undergoing unsedated colonoscopy and further explore the neuroregulatory potential of TENS-WAA technology.

Study Overview

• Status: Completed
• Conditions: Pain; Colonoscopy
• Intervention / Treatment: Device: Using an electrical stimulation device to relieve pain during colonoscopy

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

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200433
      • The First Affiliated Hospital of Naval Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

1. Inclusion Criteria:

   • Patients undergoing unsedated colonoscopy are eligible for inclusion in this study.
   • Aged 18 to 75 years.
   • Meeting the requirements for colonoscopy, with good cardiopulmonary function and stable vital signs.
   • A pre-procedural Visual Analog Scale (VAS) pain score of less than 3.

2. Exclusion Criteria:

   • Participants with speech or cognitive impairments.
   • Those with acute anal or rectal stenosis, acute perianal or rectal infections, acute diverticulitis, or active inflammatory bowel disease.
   • Women who are menstruating, pregnant, or breastfeeding.
   • Patients with active tuberculosis, hemophilia, or advanced malignant tumors.
   • Individuals with sensory disturbances, implanted pacemakers or defibrillators, or ankle skin ulcers.
   • Those who have used sedatives or analgesics either long-term or within the past 24 hours.
   • Individuals with any condition that interferes with EEG-fNIRS signal acquisition, such as cranial abnormalities, implanted metal or electronic devices, epilepsy, or neurological disorders.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Electrical stimulation group; According to the WAA theory, the selected Lower Zone 1 (LZ1) and Lower Zone 2 (LZ2) are defined as follows: LZ1 is located between the medial Achilles tendon and the medial malleolus, while LZ2 is positioned at the central inner edge of the ankle joint, near the posterior border of the tibia. Two electrode pads will be placed on each LZ1 and LZ2 of both legs, totaling eight electrode pads. The TENS-WAA device will be set to a frequency of 2 Hz, a pulse width of 500 μs, and a continuous waveform. Participants in the stimulation group will receive electrical currents at their maximum tolerable intensity below the pain threshold.	Device: Using an electrical stimulation device to relieve pain during colonoscopy; In the electrical stimulation group, the device's current intensity will be adjusted to the maximum tolerance below the participant's pain threshold, while in the control group, the current intensity will be set to the minimum.
Placebo Comparator: control group; Participants in the control group will have the electrodes placed in the same positions as those in the stimulation group, with identical electrical stimulation frequency and pulse width settings. However, the current intensity will be set to the minimum level.	Device: Using an electrical stimulation device to relieve pain during colonoscopy; In the electrical stimulation group, the device's current intensity will be adjusted to the maximum tolerance below the participant's pain threshold, while in the control group, the current intensity will be set to the minimum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EEG-fNIRS Neurovascular Coupling Peak β Coefficient	Neurovascular coupling is quantified from synchronized electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) recordings. EEG activity is decomposed into predefined delta, theta, alpha, and beta frequency bands, and band-specific power envelopes are coupled with fNIRS-derived oxygenated haemoglobin (HbO) signals within predefined cortical regions of interest. A 10-second lag is applied to account for the delayed haemodynamic response following neural activity. Coupling is estimated using a general linear model. The peak β coefficient within the predefined analysis window is used to quantify maximum EEG-fNIRS neurovascular coupling strength. Values are calculated separately for the predefined frequency bands and cortical regions of interest and compared between the distal transcutaneous electrical nerve stimulation and sham stimulation groups.	During colonoscopy, at predefined procedural stages including anal intubation, splenic flexure, hepatic flexure, and cecal intubation, within the prespecified analysis window for each stage.
EEG-fNIRS Neurovascular Coupling β Area Under the Curve	Neurovascular coupling is quantified from synchronized electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) recordings. EEG activity is decomposed into predefined delta, theta, alpha, and beta frequency bands, and band-specific power envelopes are coupled with fNIRS-derived oxygenated haemoglobin (HbO) signals within predefined cortical regions of interest. A 10-second lag is applied to account for the delayed haemodynamic response following neural activity. Coupling is estimated using a general linear model. The area under the β-coefficient curve (β AUC) within the predefined analysis window is used to quantify cumulative EEG-fNIRS neurovascular coupling strength over time. Values are calculated separately for the predefined frequency bands and cortical regions of interest and compared between the distal transcutaneous electrical nerve stimulation and sham stimulation groups.	During colonoscopy, at predefined procedural stages including anal intubation, splenic flexure, hepatic flexure, and cecal intubation, within the prespecified analysis window for each stage.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colonoscopy time		during procedure (The total time to reach the three bends and to the ileocecal valve and for the entire examination was recorded)
Pain VAS score	Pain intensity is assessed using a 10-cm Visual Analog Scale (VAS), ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain. Participants report their pain intensity at three predefined procedural stages during colonoscopy: passage of the endoscope through the rectosigmoid junction, splenic flexure, and hepatic flexure.	During colonoscopy, when the endoscope passes through the rectosigmoid junction, splenic flexure, and hepatic flexure.
EEG-Derived Cortical Neural Activity	Cortical neural activity is assessed using electroencephalography (EEG) during predefined stages of colonoscopy. After signal preprocessing and artefact removal, EEG activity is analysed in four predefined frequency bands: delta, theta, alpha, and beta. Outcome measures include relative spectral power, reflecting frequency-specific cortical activity, and pairwise EEG coherence, reflecting functional synchronization between cortical regions. Stage-specific changes relative to the corresponding resting-state reference and between-group differences are evaluated to characterize alterations in cortical neural activity and network organization associated with procedural visceral pain and distal transcutaneous electrical nerve stimulation.	During colonoscopy at predefined procedural stages, including anal intubation, splenic flexure, hepatic flexure, and ileocecal valve.
fNIRS-Derived HbO Cortical Activation	Cortical activation is assessed using oxygenated haemoglobin (HbO) signals recorded by functional near-infrared spectroscopy (fNIRS). Event-related HbO responses are analysed using a general linear model within prespecified post-event time windows. Channel-wise β coefficients are estimated relative to position-matched resting-state recordings and are used to quantify the magnitude and direction of cortical HbO activation.	During colonoscopy, at predefined procedural stages including anal intubation, splenic flexure, hepatic flexure, and cecal intubation, within the prespecified post-event analysis window for each stage.
fNIRS-Derived HbR Cortical Activation	Cortical activation is assessed using deoxygenated haemoglobin (HbR) signals recorded by functional near-infrared spectroscopy (fNIRS). Event-related HbR responses are analysed using a general linear model within prespecified post-event time windows. Channel-wise β coefficients are estimated relative to position-matched resting-state recordings and are used to quantify the magnitude and direction of cortical HbR activation.	During colonoscopy, at predefined procedural stages including anal intubation, splenic flexure, hepatic flexure, and cecal intubation, within the prespecified post-event analysis window for each stage.
fNIRS-Derived Cortical Functional Connectivity	Cortical functional connectivity is assessed from fNIRS signals during predefined stages of colonoscopy. Functional connectivity between prespecified fNIRS channels or cortical regions is quantified using pairwise correlation coefficients to characterize stage-specific changes in cortical haemodynamic network organization. Connectivity measures are compared between the distal transcutaneous electrical nerve stimulation and control conditions.	During colonoscopy, at predefined procedural stages including anal intubation, splenic flexure, hepatic flexure, and cecal intubation.

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of the Chinese People's Liberation Army Naval Medical University
• Collaborators: Shanghai Shuli Intelligent Technology Co., Ltd

Publications and helpful links

General Publications

• Wang H, Huang X, Xu L, Guo S, Gong C, Mengcheng C, Wang W, Wang H, Fang F. Analysis of the analgesic mechanism of TENS-WAA in colonoscopy using the EEG-fNIRS system: a study protocol for a randomised controlled trial. BMJ Open. 2025 Sep 30;15(9):e103681. doi: 10.1136/bmjopen-2025-103681.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2025
• Primary Completion (Actual): February 1, 2026
• Study Completion (Actual): March 15, 2026

Study Registration Dates

• First Submitted: January 16, 2025
• First Submitted That Met QC Criteria: February 6, 2025
• First Posted (Actual): February 7, 2025

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: August 11, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Acetaminophen
• Other Study ID Numbers: CHEC2025-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified individual participant data (IPD) that will be shared include:

Demographic information (age, sex, colonoscopy history)

Group allocation (TENS-WAA or sham stimulation)

Pain Visual Analogue Scale (VAS) scores at key time points

EEG and fNIRS raw and pre-processed data collected before, during, and after colonoscopy

Procedure duration and event timepoints (e.g., reaching hepatic flexure, splenic flexure, ileocecal valve)

Relevant clinical outcomes (e.g., adverse events, procedure completion status) The data will be available from the corresponding author upon reasonable request, following publication of the main results and with a signed data access agreement. No data that could directly identify individual participants will be shared.

• IPD Sharing Time Frame: The de-identified individual participant data (IPD) and supporting documents (such as data dictionaries and analysis code) will be available beginning 6 months after publication of the primary results article. Data will remain available for at least 5 years after publication, or longer if required by journal or institutional policy. Requests submitted after this period may be considered at the discretion of the corresponding author and study team.
• IPD Sharing Access Criteria: Researchers from academic institutions, hospitals, or other recognized research organizations may access the de-identified individual participant data (IPD) and supporting documents (such as data dictionary and analysis code) for legitimate scientific research purposes by sending an email request to the corresponding author. The request should briefly describe the intended research use. All requests will be reviewed by the study team to ensure ethical compliance. Data sharing will require a signed data access agreement. Only de-identified data will be shared; no information that could directly identify participants will be provided.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No