# Parabrachial role in chronic pain

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $389,687

## Abstract

Project Summary/Abstract
Chronic pain is the most common complaint of patients, affecting over 100 million Americans, and costing the
nation more than $650 billion/year in medical treatment and lost productivity. Most chronic pain patients are
resistant to pharmaceutical or surgical therapies, in large part because the underlying pathophysiology of their
chronic pain condition is unknown. The ultimate goal of this research program is to rectify this deficiency.
Most spinal cord pain-related afferents target the parabrachial nuclear complex (PB), which then projects to
multiple pain-related cortical and subcortical targets. New preliminary data indicate that inhibitory inputs
from the central nucleus of the amygdala (CeA) to PB are reduced in a rodent neuropathic pain model: chronic
constriction of the infraorbital nerve (CCI). This reduced inhibition dramatically `amplifies' both spontaneous
and evoked PB neural activity. As a consequence, there is increased PB excitation of several pain-related nuclei,
including the rostral ventral medulla (RVM), a key node of the descending pain modulation system. Based on
this exciting new evidence we hypothesize that chronic pain results from the development of a pathologic
positive feedback network: Reduced inhibition from CeA to PB –> amplified PB activity –> increased
activation of RVM neurons –> increased activation of nociceptive neurons in the spinal cord. With the use of
electrophysiological recordings from intact rodents and from brain slices, and taking advantage of behavioral
approaches, optogenetics and pharmacogenetics, we will directly test this overarching hypothesis. Specifically,
we will (1) Test the hypothesis CCI causes a progressive and significant reduction of inhibitory inputs to
nociceptive PB neurons that project to RVM, and dramatically increases their firing; (2) Test the hypothesis
that amplified PB activity is due to reduced inhibition from CeA.; (3) Test the hypothesis that reduced CeAI
inhibition to PB is causally related to the development of CCI-Pain. The anticipated findings are expected to
reveal novel mechanisms for the development of chronic pain, and may lead to development of novel therapies
to ameliorate, and perhaps even prevent, this devastating condition.

## Key facts

- **NIH application ID:** 9934292
- **Project number:** 5R01NS099245-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** ASAF KELLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $389,687
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934292

## Citation

> US National Institutes of Health, RePORTER application 9934292, Parabrachial role in chronic pain (5R01NS099245-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9934292. Licensed CC0.

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