# Developing Chemical Probes for Inflammatory Pain

> **NIH NIH R01** · ST. LOUIS COLLEGE OF PHARMACY · 2022 · $636,751

## Abstract

SUMMARY
Chronic inflammation affects millions of Americans each year and can manifest in a variety of chronic pain conditions
where normally innocuous stimuli produce pain symptoms. Long-term use of current pain therapeutics, including NSAIDS,
corticosteroids, and opioids, can cause unwanted side effects, and addiction potential can limit their utilization. Recent
studies have demonstrated a clear link between chronic low-grade inflammation and the increase in Chronic Inflammatory
Pain (CIP) conditions. Alternative therapeutic targets are needed for the treatment of these painful conditions. Nuclear
receptors, ligand-activated transcription factors that regulate a variety of physiological processes including metabolism,
inflammation, reproduction, and development, represent key drug discovery targets (second to GPCRs). The REV-ERB
proteins are nuclear receptors which function as transcriptional repressors and direct regulators of NLRP3 inflammasome
components and proinflammatory cytokines (IL-1, IL-18), and regulate the activity of macrophages at sites of cellular
damage. To date, the role of REV-ERB in relation to the manifestation of chronic pain symptoms has not been elucidated.
Due to its role in NLRP3 inflammasome and proinflammatory cytokine regulation, we hypothesize that REV-ERB is a
viable drug target for the treatment of inflammatory pain. Our strategy will leverage the known physiological functions of
REV-ERB in chronic inflammation and use a chemical biology approach to identify novel REV-ERB ligands, with superior
pharmacological profiles, to advance this potential therapy toward clinical trials. Our new preliminary data shows that total
loss of REV-ERB in mice increases mechanical hypersensitivity. Our previous studies demonstrated that pharmacological
activation of REV-ERB had no negative effects in preclinical mouse reward models, suggesting that targeting of REV-ERB
may benefit many chronic pain conditions.

## Key facts

- **NIH application ID:** 10414636
- **Project number:** 1R01NS126204-01
- **Recipient organization:** ST. LOUIS COLLEGE OF PHARMACY
- **Principal Investigator:** Bahaa Elgendy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $636,751
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414636

## Citation

> US National Institutes of Health, RePORTER application 10414636, Developing Chemical Probes for Inflammatory Pain (1R01NS126204-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10414636. Licensed CC0.

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