# A phenotypic screen for osteoarthritic pain therapeutics using all-optical electrophysiology.

> **NIH NIH R44** · QUIVER BIOSCIENCE INC. · 2020 · $892,810

## Abstract

Project Summary: A phenotypic screen for osteoarthritic pain therapeutics using all-
optical electrophysiology
Chronic pain affects over 100 million adults in the United States, many of whom cannot find
relief with current medications. Of these patients, nearly 1/3 of them suffer from osteoarthritis.
Current treatments for chronic pain include opioids and non-steroidal inflammatory agents.
However, efficacy of these drugs in chronic treatment is restricted by the development of
tolerance and dose-limiting toxicities. Opioids in particular are highly addictive, and dependency
has caused a large societal burden. Despite the clear, unmet medical need and significant
research activity, few new classes of non-opioid drugs targeting chronic pain have appeared in
the past decade.
Quell Therapeutics uses the Optopatch platform for making all-optical electrophysiology
measurements in neurons at a throughput sufficient for phenotypic screening. Using engineered
optogenetic proteins, blue and red light can be used to stimulate and record neuronal activity,
respectively. Custom microscopes enable electrophysiology recordings from 100’s of individual
neurons in parallel with high sensitivity and temporal resolution, a capability currently not
available with any other platform screening technology.
Here, we combine the Optopatch platform with an in vitro model of chronic pain, where dorsal
root ganglion (DRG) sensory neurons are bathed in a mixture of inflammatory mediators found
in the joints of osteoarthritis patients. The neurons treated with the inflammatory mixture
become hyperexcitable, mimicking the anticipated cellular pain response. We calculate the
functional phenotype of arthritis pain, which captures the difference in action potential shape
and firing rate in response to diverse stimuli. We will screen for small molecule compounds that
reverse the pain phenotype while minimizing perturbation of neuronal behavior orthogonal to the
pain phenotype, the in vitro “side effects.” We will counter-screen against neurons from the
cerebral cortex and cardiomyocytes from the heart to prioritize compounds that act selectively in
inflamed sensory neurons. The highest ranking compounds will be chemically optimized and
their pharmacokinetic, drug metabolism, and in vivo efficacy will be characterized. Our goal is to
advance therapeutic discovery for pain, which may ultimately help relieve the US opioid crisis.

## Key facts

- **NIH application ID:** 10025311
- **Project number:** 4R44AR074820-02
- **Recipient organization:** QUIVER BIOSCIENCE INC.
- **Principal Investigator:** Pin Liu
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $892,810
- **Award type:** 4N
- **Project period:** 2019-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025311

## Citation

> US National Institutes of Health, RePORTER application 10025311, A phenotypic screen for osteoarthritic pain therapeutics using all-optical electrophysiology. (4R44AR074820-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10025311. Licensed CC0.

---

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