# Characterization of Novel Neural Respiratory Circuit to Counter Opioid-Induced Respiratory Depression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $701,059

## Abstract

PROJECT SUMMARY
We have identified a novel property of the cervical spinal cord that modulates respiratory activity, both the rate
and depth of breathing, such that the respiratory drive in opioid-suppressed states in mice and humans
increases during spinal cord epidural stimulation. Respiratory rates are increased upon epidural stimulation of
specific cervical spinal cord locations when there is spontaneous breathing, and rhythmic breathing can be
generated when the respiratory state is depressed and spontaneous breathing is absent. This is an important
observation because the brainstem, which contains the rhythm-generating center for respiration, is a difficult
area for surgical and therapeutic access. If there are other accessible neural regions by surgery (i.e. epidural
stimulation) or non-invasive means (i.e. transcutaneous stimulation), for example in the cervical spine, that
influence respiration or contain their own rhythmic respiratory elements, these may represent potential
therapeutic targets to reverse opioid-induced respiratory depression. Thus, we have proposed a strategy to
characterize this novel cervical respiratory circuit. First, we will conduct extensive electrical mapping of the
respiratory responsive elements of the cervical spinal cord in mice aided by machine learning strategies, and
we will characterize the mechanistic basis for this response, the relation to opioid receptors to the respiratory
response, and identity neurons responsible for the respiratory response using optogenetic techniques. Guided
by the animal studies, we will then confirm the cervical respiratory responsive loci in humans. Third, we will
subject the identified respiratory competent regions to increasing doses of opioid to further characterize the
dose-response profile of these regions. Fourth, we will assess the feasibility and practical translation of this
strategy to reverse opioid-induced respiratory depression in three patients implanted with spinal cord
stimulators. These studies will provide an anatomical and electrophysiological characterization of the
respiratory circuit within the cervical spine and provide practical information for the treatment of opioid-induced
respiratory depression. The results obtained, especially because they are obtained in humans, will have an
immediate translational impact on our understanding of the respiratory circuit that may, in turn, prevent deaths
due to opioid overdose.

## Key facts

- **NIH application ID:** 10412972
- **Project number:** 5R01DA047637-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Daniel Lu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $701,059
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412972

## Citation

> US National Institutes of Health, RePORTER application 10412972, Characterization of Novel Neural Respiratory Circuit to Counter Opioid-Induced Respiratory Depression (5R01DA047637-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10412972. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*