Trial Outcomes & Findings for Auricular Vagus Nerve Stimulation for Chronic Pain (NCT NCT03959111)

Auricular Vagus Nerve Stimulation for Chronic Pain

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.

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.

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.

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.

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).

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.

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.

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.

Changes in inflammatory biomarker levels of PD1 between baseline and week 4