# Intrinsic Efficacy as a Determinant of Opioid Effectiveness in Treatment of Pain-Depressed Behavior

> **NIH NIH F31** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $40,352

## Abstract

PROJECT SUMMARY/ABSTRACT
Pain is a significant public health problem associated not only with unpleasant subjective sensations, but also
with behavioral depression and functional impairment that reduce normal activities of daily living (e.g. eating,
walking, working) and overall quality of life. Treatment and management strategies have become scarce as
current medications have not been effective long-term and may come with a list of side effects that limits their
use and make it difficult for patient compliance. High-efficacy opioids such as morphine which bind the mu opioid
receptor (MOR) have a historical place for the effective treatment of pain but their use has been limited due to
side effects and the opioid crisis. While the application acknowledges this, this effort neglects an alternative path
for development of safe and effective analgesics: the further development of low-efficacy MOR agonists with
sufficient efficacy to produce clinically effective analgesia with fewer and/or less severe side effects than high-
efficacy MOR agonists. The proposed project aims to utilize a novel and highly flexible strategy for selective and
precise control of net efficacy to activate MOR by testing a series of fentanyl and naltrexone (Fent/NTX) mixtures
and novel MOR selective compounds. Special focus is proposed on pain-depressed behaviors as these are
clinically translatable. Aim 1 proposes to study climbing as the pain-depressed behavioral endpoint. Five
Fent/NTX mixtures that range from high to low net efficacy at MOR and three novel compounds with MOR
selectivity and graded efficacy will be studied in the presence and absence of intraperitoneal (IP) lactic acid used
as the acute noxious stimulus. Aim 2 proposes to study dopamine changes in the nucleus accumbens using the
in vivo imaging fluorimetry technique dLight. This will be done using a subset of Fent/NTX mixtures to asses
acute pain induced by IP lactic acid and pain-independent neurochemical changes. Aim 3 proposes to further
study climbing as a pain-depressed behavior in a series of chronic pain studies. Separate groups of mice will
receive paw incision to model postsurgical pain, intraplantar complete Freund’s adjuvant (CFA) to model
inflammatory pain, repeated injection of the chemotherapy paclitaxel (PAC), and spared nerve injury (SNI) to
model neuropathic pain. As a whole, the proposed project aims to investigate the effects of Fent/NTX mixtures
as tools to investigate efficacy as a determinant of opioid treatment for acute pain-related behavioral depression
and will set the stage to study these mixtures in chronic pain states as a means for better preclinical to clinical
translation.

## Key facts

- **NIH application ID:** 10389903
- **Project number:** 1F31NS122525-01A1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Edna J Evington
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,352
- **Award type:** 1
- **Project period:** 2022-06-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389903

## Citation

> US National Institutes of Health, RePORTER application 10389903, Intrinsic Efficacy as a Determinant of Opioid Effectiveness in Treatment of Pain-Depressed Behavior (1F31NS122525-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10389903. Licensed CC0.

---

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