# Dissecting locus coeruleus contributions to stress-induced antinociception

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2021 · $33,875

## Abstract

Project Summary/Abstract
Chronic pain is the most common cause of long-term disability with an estimated 20.4% of U.S. adults had
chronic pain in 2016 and an estimated $560 billion each year in direct medical costs, lost productivity, and
disability programs. Despite this immense impact, there are insufficient therapeutic options for pain and those
that do improve patient conditions become less impactful over time. In addition, stress-induced psychological
disorders such as anxiety, depression, and pain catastrophizing have been associated with poor prognosis in
people with pain conditions. There is a need to develop alternative approaches to pain research to tackle this
systemic problem. Focusing efforts on broader neuronal systems that influence the mechanistic processes
associated with pain may be a viable novel approach. More specifically, investigating mechanisms by which
homeostatic pain processing is altered by stress will aid in isolating neurobiological underpinnings of chronic
pain. Here, we focus on the locus coeruleus norepinephrine system as a nexus of stress and pain processing.
In this proposal we will characterize the role of the LC-NE system in modulating stress-induced changes to
nociception at cellular, circuit, and network levels. We hypothesize the LC-NE system is a critical component to
the process by which stress influences nociceptive output. We will test this hypothesis in a series of experimental
aims. Aim 1 will test the hypothesis that LC-NE activity is required exclusively during the processing of an external
stressor to ultimately result in an antinociceptive effect. Aim 2 will investigate the hypothesis that LC-NE terminal
activity in the dorsal raphe nucleus (DRN) is a required step within the broader mechanism of stress-induced
antinociception. Specifically, we have proposed experiments to determine whether LC-DRN circuit activation is
potentiated in response to noxious stimuli after stress exposure and whether 1-adrenergic receptors within the
DRN are required for stress-induced antinociception. The results will provide a better understanding of how LC-
NE system activity is leveraged during both stress and pain to elicit stress-induced antinociception. This
fellowship will provide me with intensive scientific training in cell-type selective in vivo optogenetics, in vivo fiber
photometry, behavioral pharmacology, and immunohistochemistry. The combination of diverse experimental
approaches provides excellent training potential and compounded with outstanding mentorship commitment
from faculty at Washington University and external collaborators will help me achieve my career goal of becoming
an independent academic and entrepreneurial scientist.

## Key facts

- **NIH application ID:** 10315525
- **Project number:** 1F31NS124301-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Makenzie Norris
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,875
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315525

## Citation

> US National Institutes of Health, RePORTER application 10315525, Dissecting locus coeruleus contributions to stress-induced antinociception (1F31NS124301-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10315525. Licensed CC0.

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