Auricular Vagus Nerve Stimulation for Chronic Pain

Transcutaneous Auricular Vagus Nerve Stimulation for Chronic Pain

This proposal aims to investigate the treatment effect and underlying mechanism of transcutaneous acupuncture stimulation on chronic low back pain. We believe that this study, if successful, will provide new treatment options for chronic low back pain, reduce the use of opioid analgesics in chronic pain management, and enhance our understanding of the underlying mechanism of nerve stimulation treatment, as well as the pathophysiology and development of chronic pain.

Study Overview

• Status: Completed
• Conditions: Low Back Pain
• Intervention / Treatment: Other: Stimulation at Location 1; Other: Stimulation at Location 2

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Volunteers 18-65 years of age.
• Meet the Classification Criteria of chronic LBP (having low back pain for more than 6 months), as determined by a referring physician.
• Received stable treatment or no treatment in the past month.
• At least a 10th grade English-reading level. English can be a second language provided that the patients feel they understand all the questions used in the assessment measures.

Exclusion Criteria:

• Specific causes of back pain (e.g., epidural abscess, compression fracture, spondyloarthropathy, malignancy, cauda equina syndrome) or radicular pain, radiculopathy, or spinal canal stenosis. Complicated back problems (e.g., prior back surgery, medico-legal issues).
• Presence of headache/migraine, as well as widespread body pain such as fibromyalgia.
• The intent to undergo surgery during participation in the study.
• History of cardiac, respiratory, or nervous system disease that, in the investigator's judgment, precludes participation in the study because of a heightened potential for adverse outcomes (e.g., asthma or claustrophobia).
• Presence of any contraindications to MRI scanning (e.g., cardiac pacemaker, metal implants, fear of enclosed spaces, pregnancy, cannot lie still in fMRI scanner).
• Conditions that might confound longitudinal effects or interpretation of results (e.g. severe fibromyalgia, rheumatoid arthritis).
• Pregnant or lactating.
• Conditions making study participation difficult (e.g., paralysis, psychoses, or other severe psychological problems as per the judgment of a study investigator during Session 1).
• Active substance abuse disorders within the last 24 months (based on subject self-report).
• Use of prescription steroids for pain during the past six months.
• Presence of any other acute or chronic pain disorder.
• Any medical conditions, such as peripheral neuropathy, that could affect the results of QST.

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: Ear stimulation (Location 1)	Other: Stimulation at Location 1; Stimulation parameters will include 1) density wave adjusted to 20Hz with less than 1 ms pulse width, 2) intensity adjusted based on the tolerance of the patient (moderate tolerable stimulation without pain), and 3) treatment will be applied 1 time per day, 5 times per week for four weeks (on-site tVNS treatment plus self-administration at home).
Experimental: Ear stimulation (Location 2)	Other: Stimulation at Location 2; Stimulation parameters will include 1) density wave adjusted to 20Hz with less than 1 ms pulse width, 2) intensity adjusted based on the tolerance of the patient (moderate tolerable stimulation without pain), and 3) treatment will be applied 1 time per day, 5 times per week for four weeks (on-site tVNS treatment plus self-administration at home).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low Back Pain Intensity	This is a uni-dimensional measure of chronic low back pain intensity. It uses an 11-point numeric scale (0 indicate no pain, and 10 indicates max level of pain that can be imagined). We will use it to measure the patient's average pain intensity in the past week, which will be measured at the beginning and end of the study.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Roland-Morris Disability Questionnaire Score	The Roland-Morris Disability Questionnaire (RMDQ) is a widely used self-reported measure of physical disability specifically designed for individuals with low back pain. The questionnaire assesses the impact of back pain on daily activities. The total score ranges from 0 to 24, where: 0 indicates no disability, 24 indicates severe disability.	1 months
Patient-Reported Outcomes Measurement Information System (PROMIS) Scores	The PROMIS, funded by the NIH, is a system containing reliable, flexible, precise, and responsive assessment tools that have been widely validated in numerous samples. 29 items covering seven domains and one additional question about pain intensity. Here we focus on Pain Interference (4 items, raw score range 4-20, T-score range roughly 41-76, mean and SD in chronic pain patients is 67.1 and 5.79. The 67.1indicates the population mean in chronic pain patients with a standard deviation of 5.79 based on publication PMCID: PMC8412832). Higher T-scores = more pain interference. We compared pre- and post-treatment difference of the pain interference subscore.	baseline and post-treatment
Pain Catastrophizing Scale	The Pain Catastrophizing Scale (PCS) is a 15-item questionnaire assessing the extent to which individuals magnify the threat of pain and feel helpless in the presence of pain. Due to an administration error, the full 15-item PCS was not collected as intended: participants received an incomplete version of the questionnaire (missing items), which prevents calculation of valid total and subscale scores. This error occurred during data collection and affected all attempted administrations (including both planned time points, where applicable); therefore, no participants have analyzable PCS data to report for this outcome measure.	baseline and post-treatment
The Pennebaker Inventory of Limbic Languidness	The Pennebaker Inventory of Limbic Languidness (PILL) is a self-report questionnaire assessing the frequency of common physical symptoms. Participants rate how often they have experienced each symptom over a specified retrospective period using a 5-point Likert scale. The PILL includes a broad range of symptoms, including pain-related items (e.g., headache, back pain, sore muscles). The PILL was administered at baseline only to characterize baseline symptom sensitivity/awareness and to reduce participant burden. Total scores are computed as the sum of 53 items rated from 1-5 (total score range: 53-265), with higher scores indicating more frequent symptoms (worse outcome) and lower scores indicating less frequent symptoms (better outcome).	Baseline
Resting State Functional Connectivity Changes of the PAG	Resting state functional connectivity refers to the statistical relationship between the time-series activity of different brain regions as measured by functional MRI (fMRI). Functional connectivity changes of the periaqueductal gray (PAG) at rest refer to alterations in the neural communication between the PAG and other brain regions when a subject is not actively engaged in a task. The PAG, located in the midbrain, plays a critical role in pain modulation, defensive behavior, and autonomic regulation.	1 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting State Functional Connectivity of the Medial and Lateral Hypothalamus	Resting state functional connectivity refers to the statistical relationship between the time-series activity of different brain regions as measured by functional MRI (fMRI). Functional connectivity changes of the medial and lateral hypothalamus at rest refer to alterations in the neural communication between the two regions and other brain regions when a subject is not actively engaged in a task.	1 month
CBF as Measured by ASL	Changes in cerebral blood flow were evaluated by comparing pre-to-post change between the real and sham groups. Statistically significant clusters identified in this comparison are reported in the Results Data Tables, including a cluster located in the precentral gyrus.	1 month
Inflammation Biomarkers	Changes in inflammatory biomarker levels of PD1 between baseline and week 4	1 month

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Jian Kong, Massachusetts General Hospital

Publications and helpful links

General Publications

• Li Y, Li T, Yan K, Wu J, Reddy S, Sacca V, Ursitti AK, Zhu M, Hodges S, Chen L, Kong J. Both Transcutaneous Auricular Vagus Nerve Stimulation and Great Auricular Nerve Stimulation Modulate Functional and Structural Connectivity of Brainstem Nuclei in Chronic Low Back Pain. Neuromodulation. 2025 Oct 15:S1094-7159(25)01025-6. doi: 10.1016/j.neurom.2025.08.415. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2019
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): April 30, 2024

Study Registration Dates

• First Submitted: May 20, 2019
• First Submitted That Met QC Criteria: May 20, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Low Back Pain
• Other Study ID Numbers: 2016P000678

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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