# Understanding the Mechanistic, Neurophysiological, and Antinociceptive Effects of Transcutaneous Auricular Neurostimulation for Treatment of Chronic Pain

> **NIH NIH RM1** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2024 · $1,753,199

## Abstract

Project Summary/Abstract
Despite growing urgency to transition many chronic pain patients off prescription opioids, there is limited
evidentiary support and mixed success rates for alternative treatment approaches that aim to facilitate
discontinuation. Few patients who initiate opioid tapers succeed, and a subset of patients react adversely to
dose reductions, experiencing significantly worsened pain and psychological destabilization. This is particularly
true with patients on prolonged opioid therapy, in which the effects of physiological dependence alter
functioning within the neural pain matrix towards a dysregulated and hypersensitized state. Neuromodulation
approaches are particularly well suited for this clinical challenge, offering safe and effective analgesia as well
as mitigation of opioid withdrawal syndrome. In particular, the Sparrow Therapy System is an FDA-cleared
device that delivers transcutaneous auricular neurostimulation (tAN) to the vagal and trigeminal nerves and is
therapeutically indicated for pain during opioid withdrawal. Yet, the mechanisms of action remain poorly
understood. The absence of an accepted mechanistic model poses limits on tAN clinical application, as an
understanding of the neurophysiological mechanisms supporting analgesia would enable parameter
optimization leading to precision implementation and maximized therapeutic benefit. We hypothesize that the
effects of our tAN approach are 1) dependent on endogenous opioid neurotransmission, 2) are maximally
engaged by simultaneous vagal and trigeminal stimulation, and 3) confer analgesic benefits associated with
increased neural activity in brainstem vagal afferents but decreased activation in cortical and subcortical pain
network regions. To elucidate these proposed mechanisms, we offer a synergistic series of studies in healthy
adults and chronic pain patients. Aim 1 will use an experimental µ-opioid blockade paradigm and a novel
concurrent pain and functional magnetic resonance imaging (fMRI) paradigm to assess brain activation and
pain thresholds following auricular vagal and trigeminal stimulation presented alone and in combination. Aim 2
will likewise entail a concurrent neurostimulation and fMRI paradigm to observe the direct brain effects of
auricular vagus stimulation, auricular trigeminal stimulation, combination stimulation, or sham stimulation.
Using a double-blind, sham-controlled clinical mechanistic trial of tAN in pain patients undergoing acute opioid
tapering, Aim 3 will establish the specific neurophysiological signature of tAN-based analgesia and differentiate
this activation profile from secondary outcomes. Our interdisciplinary approach and diverse scientific team of
bioengineers, neuroscientists, and clinical pain and opioid specialists is well suited for accomplishing these
goals. Results of this project will deliver specific therapeutic mechanisms of action of an emerging treatment
that will expand benefits for a high-need clinical popul...

## Key facts

- **NIH application ID:** 10900731
- **Project number:** 5RM1NS128787-03
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Jeffrey J Borckardt
- **Activity code:** RM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,753,199
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900731

## Citation

> US National Institutes of Health, RePORTER application 10900731, Understanding the Mechanistic, Neurophysiological, and Antinociceptive Effects of Transcutaneous Auricular Neurostimulation for Treatment of Chronic Pain (5RM1NS128787-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10900731. Licensed CC0.

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