Developing chemical probes for inflammatory pain

Active Project Grant Awarded Last action

Award ID
R01NS126204
Recipient
Awarding agency
Obligated
$5,555,761

Award facts

Completion date 74% complete
Originally
Place of performance
St. Louis, MO 63110, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
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.

Transactions

Action Obligated Date
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Amendment $636,751
Original award $636,751
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Subawards

Subrecipient Amount Awarded
Auburn University Sponsor: Washington University in St. Louis Prime Sponsor: NIH – NINDS Project Title: Developing Chemical Probes for Inflammatory Pain STATEMENT OF WORK Dr.… $781,289
University Of Health Sciences And Pharmacy In ST. Louis Scope of Work Subcontract from Washington University School of Medicine in St. Louis to the University of Health Sciences and Pharmacy in Saint Louis with… $255,031

Quick answers

Who received award R01NS126204?

R01NS126204 was awarded to The Washington University by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on August 1, 2022.

How much is award R01NS126204 worth?

$5,555,761 has been obligated on R01NS126204.

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