Transauricular Vagus Nerve Stimulation Frequencies for Postoperative Pain (TVNS-PAIN)

Effects of Different Frequencies of Transauricular Vagus Nerve Stimulation on Postoperative Pain: A Randomized, Double-Blind, Sham-Controlled Trial With Preoperative and Postoperative Sessions

The goal of this clinical trial is to learn whether different frequencies of transauricular vagus nerve stimulation (tVNS) can reduce postoperative pain and opioid consumption in adults undergoing abdominal or urologic surgery. It will also evaluate the effects of tVNS on recovery quality, autonomic function, and treatment safety. The main questions it aims to answer are:

Does transauricular vagus nerve stimulation reduce postoperative opioid consumption during the first 24 hours after surgery? Do different stimulation frequencies (high-frequency and low-frequency tVNS) produce different effects on postoperative pain and autonomic responses? Is transauricular vagus nerve stimulation safe and well tolerated in surgical patients?

Researchers will compare high-frequency tVNS, low-frequency tVNS, and sham stimulation (inactive stimulation) to determine their effects on postoperative pain and opioid requirements.

Participants will:

Be randomly assigned to receive high-frequency tVNS, low-frequency tVNS, or sham stimulation.

Receive two 30-minute stimulation sessions, one before anesthesia and one after surgery in the post-anesthesia care unit.

Undergo assessments of postoperative pain, opioid consumption, need for rescue analgesics, postoperative nausea and vomiting, heart rate changes, and quality of recovery.

Be monitored for adverse events related to the intervention during the study period.

A total of 174 participants will be enrolled in this single-center, randomized, double-blind, sham-controlled clinical trial.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Pain; Postoperative Nausea and Vomiting (PONV); Opioid Consumption, Postoperative
• Intervention / Treatment: Device: Transauricular Vagus Nerve Stimulation (tVNS); Device: Sham Transauricular Vagus Nerve Stimulation (sham tVNS)

Detailed Description

Postoperative pain remains a major challenge in perioperative care and is associated with delayed recovery, increased healthcare utilization, and greater opioid consumption. Despite advances in multimodal analgesia, opioid medications continue to play a central role in postoperative pain management and may be associated with adverse effects such as nausea, vomiting, respiratory depression, and prolonged recovery. Therefore, the development of effective non-pharmacological adjunctive strategies is of considerable clinical interest.

Transauricular vagus nerve stimulation (tVNS) is a non-invasive neuromodulation technique that stimulates the auricular branch of the vagus nerve through the external ear. Experimental and clinical studies suggest that vagal stimulation may modulate pain perception through activation of central autonomic pathways, enhancement of descending inhibitory pain mechanisms, and regulation of inflammatory responses. Previous clinical trials have demonstrated promising effects of tVNS on acute and chronic pain conditions, including reductions in postoperative pain scores.

However, the optimal stimulation parameters for perioperative analgesia remain uncertain. In particular, the influence of stimulation frequency on clinical outcomes and autonomic responses has not been adequately investigated. Different stimulation frequencies may activate distinct neural pathways and produce different effects on pain modulation and autonomic regulation.

This study is designed to evaluate the effects of different frequencies of transauricular vagus nerve stimulation applied before and after surgery in adult patients undergoing elective surgical procedures. In addition to assessing postoperative opioid requirements, the study will explore the relationship between autonomic responses and postoperative recovery. The findings may contribute to the optimization of non-pharmacological analgesic strategies and support the incorporation of transauricular vagus nerve stimulation into multimodal perioperative pain management protocols.

• Study Type: Interventional
• Enrollment (Estimated): 174
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rodrigo L Alves, MD, PhD; Phone Number: 71 99961-9818; Email: rlalves@ufba.br
• Study Contact Backup: Name: João Paulo A de Carvalho; Phone Number: 75 98295-3834; Email: joaoaureliano@ufba.br

Study Locations

• Brazil
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40170-110
      • Recruiting
      • Hospital Universitário Professor Edgard Santos, Federal University of Bahia (HUPES-UFBA)
      • Contact: João Paulo A Carvalho; Phone Number: 75982953834; Email: joaoaureliano@ufba.br

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults aged 18 to 59 years.
• Undergoing elective abdominal or urologic surgery.
• American Society of Anesthesiologists (ASA) physical status I-III.
• Able and willing to provide written informed consent.

Exclusion Criteria:

• History of neurological disorders.
• History of psychiatric disorders.
• Inability to understand study procedures.
• Pregnancy.
• Cognitive impairment.
• Communication difficulties that interfere with study assessments.
• Auricular dermatitis or skin lesions at the stimulation site.
• Pre-existing cardiac arrhythmia.
• Chronic opioid use.
• Implanted electronic medical devices, including pacemakers.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Frequency tVNS; Participants will receive active transauricular vagus nerve stimulation (tVNS) at a frequency of 60-120 Hz. Stimulation will be applied bilaterally to the auricular branch of the vagus nerve for 30 minutes before anesthesia and for 30 minutes after surgery. Current intensity will be adjusted between 2 and 6 mA according to participant tolerance.	Device: Transauricular Vagus Nerve Stimulation (tVNS); Non-invasive electrical stimulation of the auricular branch of the vagus nerve applied bilaterally through ear electrodes. Stimulation is delivered before anesthesia and after surgery using predefined frequency settings.
Experimental: Low-Frequency tVNS; Participants will receive active transauricular vagus nerve stimulation (tVNS) at a frequency of 10-20 Hz. Stimulation will be applied bilaterally to the auricular branch of the vagus nerve for 30 minutes before anesthesia and for 30 minutes after surgery. Current intensity will be adjusted between 2 and 6 mA according to participant tolerance.	Device: Transauricular Vagus Nerve Stimulation (tVNS); Non-invasive electrical stimulation of the auricular branch of the vagus nerve applied bilaterally through ear electrodes. Stimulation is delivered before anesthesia and after surgery using predefined frequency settings.
Sham Comparator: Sham tVNS; Participants will receive sham transauricular vagus nerve stimulation. The device will be positioned and activated to mimic active treatment, but stimulation will be discontinued shortly after initiation. Participants will undergo two 30-minute sessions, one before anesthesia and one after surgery, while maintaining blinding to treatment allocation.	Device: Sham Transauricular Vagus Nerve Stimulation (sham tVNS); Sham stimulation delivered using the same device and electrode placement as active stimulation. The device is activated to mimic treatment but does not deliver therapeutic electrical stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total postoperative opioid consumption during the first 24 hours after surgery	Total opioid consumption during the first 24 postoperative hours, recorded according to the institutional postoperative analgesia protocol.	24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain intensity (VAS)	Pain intensity measured using a 100-mm Visual Analog Scale (VAS). Pain scores will be assessed at predefined postoperative time points and compared among study groups.	Before stimulation in the post-anesthesia care unit, immediately after stimulation, 2 hours after surgery, and 24 hours after surgery
Rescue analgesic use	Number of participants requiring rescue analgesics and total rescue analgesic administration during the first 24 postoperative hours.	Within 24 hours after surgery
Postoperative nausea and vomiting (PONV)	Incidence of postoperative nausea and/or vomiting and use of rescue antiemetic medication during the postoperative period.	Within 24 hours after surgery
Heart rate changes	Changes in heart rate measured immediately before and immediately after transauricular vagus nerve stimulation sessions as an indicator of autonomic nervous system activity.	Immediately before and immediately after each stimulation session (preoperative and postoperative).
Quality of Recovery (QoR-15 Score)	Quality of postoperative recovery assessed using the 15-item Quality of Recovery questionnaire (QoR-15). Higher scores indicate better recovery.	Baseline (preoperative) and 24 hours after surgery.
Adverse events related to transauricular Vagus Nerve Stimulation	Incidence of adverse events potentially related to the intervention, including auricular discomfort, skin irritation, headache, bradycardia, hypotension, bronchospasm, or other treatment-related events.	From the first stimulation session until 24 hours after surgery.

Collaborators and Investigators

• Sponsor: Federal University of Bahia
• Collaborators: Faculdade de Medicina de Botucatu, UNESP, Botucatu, Brasil
• Investigators: Principal Investigator: Rodrigo M Vieira, MD, Botucatu Medical School, São Paulo State University (UNESP)

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 4, 2026

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Postoperative Pain; Neuromodulation; Randomized Controlled Trial; Opioid Consumption; Pain Management; tVNS; Transauricular Vagus Nerve Stimulation
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Signs and Symptoms, Digestive; Neurobehavioral Manifestations; Perceptual Disorders; Vomiting; Nausea; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Postoperative Nausea and Vomiting; Agnosia
• Other Study ID Numbers: 96691226.0.0000.0049 (Registry Identifier: 8.416.413)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in publications arising from this study will be made available, including demographic characteristics, intervention allocation, primary and secondary outcome measures, and adverse event data. Data will be shared only after removal of all direct identifiers to protect participant confidentiality.
• IPD Sharing Access Criteria: De-identified data will be available to qualified researchers who provide a methodologically sound research proposal. Requests should be submitted to the principal investigator. Access will be granted following review and approval of the proposed use and execution of a data-sharing agreement.

Drug and device information, study documents

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