# MIXED NOP/MU COMPOUNDS AND THE INVOLVEMENT OF THEIR RECEPTORS IN ANALGESIA

> **NIH NIH R01** · FLORIDA ATLANTIC UNIVERSITY · 2020 · $452,881

## Abstract

The NOP receptor, the fourth member of the opioid receptor family, has been the target of investigation
since its discovery in 1993, with respect to pharmacology, anatomy, and behaviors elicited by agonists and
antagonists. Despite considerable research efforts, the lack of suitable receptor antibodies has prevented the
appropriate interpretation of many studies pertaining to the details of receptor location, internalization, and
dimerization. In order to test hypotheses pertaining to NOP receptor function, Dr. Brigitte Kieffer and
colleagues have generated knock-in mice that carry green fluorescent protein (eGFP) coupled to the NOP
receptor. Similar GFP-tagged delta receptor and mCherry-tagged mu receptor knock-in mice have proven very
useful in understanding the relationship among anatomy, cellular localization, and function of delta and mu
opioid receptors. Like the mu receptor, NOP receptors are found in very high numbers in all of the pain-related
brain regions, including PAG, RVM, MHb, thalamus, etc. However, NOP receptors are unlike the other
members of the opiate receptor family in that NOP receptor agonists block opiate analgesia when administered
i.c.v. while having antinociceptive activity when administered intrathecally. In addition, NOP receptor agonists
appear to be more effective rather than less effective in chronic pain states. This is surprising since NOP
receptor mRNA decreases in DRG and anterior cingulate cortex (ACC) and NOP receptors decrease in certain
spinal cord laminae in spinal nerve ligated mice. Using NOP-eGFP(+/+) mice, immunohistochemical experiments
will be carried out to better understand the circuitry and the cellular localization in brain, spinal cord, and DRG
that leads to these unusual properties of N/OFQ and other NOP receptor agonists. These will be correlated
with behavioral experiments subsequent to microinjections into specific brain regions to understand how NOP
receptor activation modulates the sensory as well as the affective component of pain. Specific Aim 1 will
carefully examine the location of NOP-eGFP receptors in DRG as well as determine the pain modalities (heat,
cold, touch) attenuated by systemic administration of NOP agonists and antagonists and determine how these
parameters change during chronic neuropathic and inflammatory pain. Specific Aim 2 will examine spinal cord
NOP-eGFP expression as well as characterize spinal projections both to the brain and to the periphery.
These results will be compared with the effects of NOP agonists on different pain modalities after intrathecal
administration in sham and neuropathic mice. Specific Aim 3 will examine neuropathic pain-induced changes
in NOP-eGFP receptor levels in brain with particular emphasis on regions involved in the sensory (PAG) and
affective (ACC) components of pain. Direct injections of NOP receptor agonists and antagonists into these
brain regions will be used to better understand the NOP receptor-related circuitry that modulates t...

## Key facts

- **NIH application ID:** 9980820
- **Project number:** 5R01DA023281-13
- **Recipient organization:** FLORIDA ATLANTIC UNIVERSITY
- **Principal Investigator:** LAWRENCE R TOLL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $452,881
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980820

## Citation

> US National Institutes of Health, RePORTER application 9980820, MIXED NOP/MU COMPOUNDS AND THE INVOLVEMENT OF THEIR RECEPTORS IN ANALGESIA (5R01DA023281-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980820. Licensed CC0.

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