# Validating ASCT2 for the Treatment of Chronic Postsurgical Pain

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $1,545,000

## Abstract

Pain associated with surgery is experienced by millions of patients every year. Post-surgical
pain usually resolves as the surgical site heals. However, up to half of the patients develop
chronic pain after surgery. Crucially, little is known about the mechanisms that aid in the
resolution of postoperative pain. Moreover, opioids remain the mainstay treatment for post-
surgical pain which are fraught with serious side-effects and crucially - abuse liabilities. The goal
of our research is to validate an endogenous mechanism that leads to the resolution of post-
surgical pain. Metabolism is inextricably linked to every aspect of cellular function. However,
the specific effects surgery has on the metabolism of sensory neurons and how these changes
influence the resolution of post-surgical pain are not known. Hence, we determined that surgical
trauma suppresses pyruvate oxidation while increase glutamine catabolism was associated with
the resolution of post-surgical pain. The selective increase of glutamine oxidation was in part
mediated by the glutamine transporter ASCT2 which replenished the Krebs cycle metabolic
intermediates that have been depleted due to reduced pyruvate oxidation. This process is
known as anaplerosis. Moreover, disruption of ASCT2 expression prevented the resolution of
postoperative pain. Hence, we aim to validate that ASCT2 is critical for the resolution of post-
surgical pain and can be manipulated for the resolution of postoperative pain. Using molecular,
biochemical, metabolic assays and innovative multiband fluorescence imaging method of intact
DRGs, we aim to achieve our objective. Moreover, we propose to validate an innovative RNA-
based strategy that enhances ASCT2 expression. Validation of endogenous targets that resolve
postoperative pain can have broad impact in advancing our knowledge of the transition of acute
pain to chronic and lead to urgently needed public health advancements.

## Key facts

- **NIH application ID:** 9974791
- **Project number:** 1R01NS116759-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Ohannes Kevork Melemedjian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,545,000
- **Award type:** 1
- **Project period:** 2020-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974791

## Citation

> US National Institutes of Health, RePORTER application 9974791, Validating ASCT2 for the Treatment of Chronic Postsurgical Pain (1R01NS116759-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974791. Licensed CC0.

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