Effects of external ear stimulation on pain perception and mood

National Center For Complementary & Integrative Health

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Abstract

This was the sixth year of the Pain Research Center, a trans-NIH core that provides resources to investigators across NIH Institutes to conduct rigorous experiments and clinical studies focused on pain and its treatment. The Center continued to progress, recruit new leadership, and plan new studies in FY25. This progress report describes progress on our main human subjects protocol "Ear stimulation, pain and mood." The protocol will continue to recruit healthy men and women for a randomized, controlled, double-blind study that requires 3 separate visits: 1 screening visit, and 2 subsequent visits for the experimental sessions. In a within-subject, cross-over design, the response to experimentally induced heat pain is examined before, during, and after transcutaneous (non-invasive) vagus nerve stimulation (via a region of the ear exclusively innervated by the vagus nerve) compared to stimulation of the earlobe (control site; innervated by cervical spinal nerves). The following data are collected before, during, and after experimental and control stimulation of the left external ear: warm sensation and heat pain thresholds, and ratings of mood, pain intensity and unpleasantness after short and long duration heat pain stimuli. Autonomic measures (heart rate, respiration, blood pressure, and skin conductance) are also collected throughout the study session. This study will allow us to address the following questions: 1. Does the experimental condition (vagus stimulation) compared to the control condition (earlobe stimulation) significantly decrease pain perception? 2. Does the experimental condition, compared to control, significantly improve mood? 3. Does mood mediate the effects of vagus stimulation on pain perception? In addition, we will determine whether vagus stimulation, compared to control, increases heart rate variability. We have completed 95% of our target enrollment and are preparing for data cleaning and analysis. We will submit our main findings to a high-impact journal in FY26, and present our findings at leading scientific conferences. Prescreening for this protocol is conducted under 16-AT-0077, which has contributed to the development of a normative data sample for pain phenotyping under 16-AT-0077. Working closely with the NCCIH Office of the Clinical Director, we have supported clinical pain research across NIH, in addition to this protocol. We have 1) piloted new technologies (fNIRS) for identifying brain signature of pain in persons who are not able to undergo MRI or verbally communicate, 2) developed and implemented QST protocols to support clinical investigations of pain mechanisms in various patient populations, 3) collected, analyzed, and interpreted MRI/fMRI data to uncover relationships between pain and fatigue, 4) assisted with study planning and protocol writing for three I-HEAL funded projects. We have one manuscript under review that reports on findings from collaborative efforts with NIDCR to investigate pain phenotypes in patients with fibrous dysplasia, and our preparing to submit an abstract to present at the Society for Neuroscience in 2025. In FY25 we completed piloting for a study to identify neural pain signatures using fNIRS to be implemented in future studies to develop reliable and valid pain assessments in persons with intellectual disabilities or who are unable to report pain. Our preliminary findings support the use of fNIRS to detect a reliable cortical pain signature and will be further tested in patient populations to confirm its validity under a new protocol. The Lead Investigator who was leading these efforts resigned in Spring 25, yet these efforts have continued with minimal impact.