# Clinical Translation of Ultrasonic Ketamine Uncaging for Non-Opioid Therapy of Chronic Pain

> **NIH NIH UG3** · STANFORD UNIVERSITY · 2024 · $129,968

## Abstract

Project Summary and Narrative
Many mental health and neurological diseases have significant affective components of their
disease and/or significant comorbidities with affective disorders, such that treating the affective
component of the disease is beneficial for treating the whole disease process. In the parent award
of this proposal, ultrasonic uncaging of ketamine will be applied to the anterior cingulate cortex of
patients with chronic pain to treat the affective component of this disorder – to modulate how
severe the patient experiences pain, less so modulating whether they experience pain in the first
place. This same strategy could in principle be applied to other neuropsychiatric disorders that
have a strong affective component. In particular opioid use disorder (OUD) is a significant cause
of morbidity and mortality worldwide with a strong affective component. Traditional treatments like
buprenorphine or methadone often fail to address the mood disturbances associated with OUD,
leading to high relapse rates. Specifically, the withdrawal/abstinence period of OUD is associated
with a negative affective state, dubbed ‘hyperkatifeia,’ that predisposes to relapse later. Like in
the chronic pain application, ketamine uncaging targeted to a critical brain region could treat the
affective component of substance use disorders, including OUD, to break the cycle of binge,
withdrawal, and relapse that defines the disorder.
In this training period, the candidate will explore the use of ultrasonic ketamine uncaging to
modulate affective behaviors in rodent models of chronic pain as well as of OUD. This activity will
better define the protocols for ultrasonic ketamine uncaging to be used in the clinical trial phase
of the parent award, guide interpretation of the clinical and physiologic data in that clinical trial
phase, and generate data to suggest further applications of ketamine uncaging, and the use of
ultrasonic uncaging more broadly to treat affective disorders and the affective component of
neuropsychiatric disease. During the preclinical phase of the parent award, the candidate will gain
training in in vivo application of therapeutic ultrasound, neurobehavioral assay development and
implementation, quantitative video behavioral analysis, functional ultrasound imaging, and
neuroscientific data analysis. For the clinical phase of the parent award it is anticipated that the
candidate will stay with the investigatory group, with or without a successful extension of this
funding, to gain training in the clinical use of therapeutic ultrasound and neuropsychological trial
implementation.

## Key facts

- **NIH application ID:** 11090278
- **Project number:** 3UG3NS115637-03S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Raag D Airan
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $129,968
- **Award type:** 3
- **Project period:** 2019-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11090278

## Citation

> US National Institutes of Health, RePORTER application 11090278, Clinical Translation of Ultrasonic Ketamine Uncaging for Non-Opioid Therapy of Chronic Pain (3UG3NS115637-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11090278. Licensed CC0.

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