# Design of genetically encoded sensors for detecting endogenous opioid peptides

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $337,405

## Abstract

Design of genetically encoded sensors for detecting endogenous opioid peptides
 Opioids that target the mu-opioid receptors (MOR) remain the most effective pain medication but
with severe side effects, such as addiction, constipation and respiratory suppression. The side effects
result from a lack of specificity for the MOR in the pain modulation circuit by currently available opioids.
Since endogenous opioid peptides do not lead to such adverse effects, understanding their role in different
neuronal circuits could advance our knowledge of how opioid peptides act differently, and possibly facilitate
the design of novel pain medications with reduced side effects. To study how endogenous opioid peptides
exert their effects on different neural circuits, we need to detect when and where the endogenous opioid
peptides are released in the brain at a high spatiotemporal resolution and at the circuit level. Microdialysis,
the best available method for detecting opioid peptides in the mouse brain, can detect opioid peptides with
a spatial resolution of ~ 400 µm and a temporal resolution of ~20 minutes. However, neuron somas are ~
20 µm and neuromodulating peptides are usually released and function on the order of seconds to minutes.
There is a need of methods to detect the endogenous opioid peptide release with higher spatiotemporal
resolution. Therefore, we propose to design two classes of opioid sensors: 1) A transcriptional reporter
that will enable the detection of the endogenous opioid peptides at a cellular resolution across a large
volume of the brain tissue for studying how endogenous opioid peptides exert their effects at the circuit
level; 2) Real time fluorescent sensors that will enable the detection of the endogenous opioid peptides
with subcellular spatial resolution and a temporal resolution on the order of seconds. These two sensors
will complement each other to address the long unanswered questions regarding the endogenous opioid
peptide regulation and signaling. For example, what kind of pain and reward stimuli will stimulate the opioid
peptide release? Where exactly are the opioid peptides released at a cellular or sub-cellular resolution in
response to different pain and reward stimuli? How soon after pain or reward stimuli are endogenous opioid
peptides released? Completion of this proposal will contribute to our long-term goal of designing tools to
advance our understanding of the endogenous opioid signaling for designing pain medications with mini-
mum side effects.

## Key facts

- **NIH application ID:** 10363913
- **Project number:** 1R01DA053200-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Wenjing Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $337,405
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10363913

## Citation

> US National Institutes of Health, RePORTER application 10363913, Design of genetically encoded sensors for detecting endogenous opioid peptides (1R01DA053200-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10363913. Licensed CC0.

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