# Interoception and Pain: Noradrenergic Modulation of Nociceptive Transmission in the Parabrachial Nucleus

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $446,446

## Abstract

Project Summary/Abstract
Chronic stress is comorbid with a wide spectrum of conditions, such as anxiety, depression, sleep disturbances,
and pain. Chronic stress plays a crucial role in exacerbating pain and the loss of quality of life. The mechanisms
by which stress exacerbate pain, and how these mechanisms contribute to nervous system pathology, are
poorly understood. The ultimate goal of this proposal is to rectify this deficiency.
In this application, we study how interoceptive and somatic pain inputs interact within lateral parabrachial
(PBl) circuits to affect behavioral responses to pain. We focus on interoceptive inputs from catecholaminergic
neurons with the caudal mediodoral nucleus of the solitary tract (NTS) because these neurons play a pivotal
role in facilitating behavioral responses to stress and emotional stimuli. We Hypothesize that chronic stress
potentiates catecholaminergic NTS (NTScat) inputs to PBl and amplifies nociceptive signaling within PBl,
resulting in enhanced behavioral responses to pain. We propose 3 aims:
Aim 1: Noxious stimuli activate the NTScat èPBl circuit in naïve animals. We predict that: (1A) Noxious
stimuli enhances NTScat neuronal activity; (1B) Optogenetic activation of NTScat neurons causes NA release in
PBl; and (1C) Reversible inactivation of NTScat neurons results in diminished release of NA in PBl in response
to noxious stimulation.
Aim 2: Chronic stress alters dynamics of NA release from NTScat terminals in PBl. In an animal model of
chronic stress we predict: (2A) NA release in PBl evoked by noxious stimulation is enhanced by chronic stress;
(2B) PBl neuron responses to noxious stimuli are enhanced by chronic stress; inactivation of NTScat inputs to
PBl attenuates these responses; and (2C) Suppression of NTScat inputs to PBl attenuates the effects of chronic
stress on pain-related behaviors.
Aim 3: NA released by NTScat terminals presynaptically regulates sensory and affective pain inputs to PBl and
increases its excitability. We predict that NA released from NTScat afferents: (3A) Has a prolonged faciliatory
effect on spontaneous synaptic activity in PBl; (3B) Suppresses inhibitory inputs from the central nucleus of the
amygdala to PBl; and (3C) Facilitates excitatory inputs to PBl neurons from superficial dorsal horn afferents.

## Key facts

- **NIH application ID:** 10800758
- **Project number:** 5R01NS127827-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Nathan P Cramer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $446,446
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10800758

## Citation

> US National Institutes of Health, RePORTER application 10800758, Interoception and Pain: Noradrenergic Modulation of Nociceptive Transmission in the Parabrachial Nucleus (5R01NS127827-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10800758. Licensed CC0.

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