# Deconstructing the network mechanisms of chronic pain and reward in the amygdala

> **NIH NIH R00** · UNIVERSITY OF PENNSYLVANIA · 2021 · $245,872

## Abstract

Summary
Chronic pain is not merely a persistent sensory disorder, but a neurological disease of affective dysfunction
that negatively impacts the mental state, professional goals, and personal relationships of over 100 million
Americans. Emotionally-guided behaviors, such as avoiding pain and seeking pleasure, are derived from
valence information generated by the limbic brain. The ability of valence circuits to categorize external and
internal sensory information as either ‘pleasant’ or ‘unpleasant’ is essential for behavior selection, protective
learning, and survival. However, miscoding of sensory information due to pathological plasticity within these
valence circuits can produce unwanted psychological effects, including the suffering and depression
associated with chronic pain. The amygdala is a brain region critical for processing emotional valence and
influencing motivational drive. However, the functional relevance of amygdalar valence processing to the
generation of hedonic perception and behavior-selection is defined primarily by its output connectivity with
effector structures in limbic and cortical regions. Recent evidence proposes the existence of innate and distinct
neuronal circuits for opposing positive and negative valence processing in the basolateral nucleus of the
amygdala (BLA) that also diverge based on the downstream target structures, such as the nucleus accumbens
(NAc). However the network-level interface between these opposing BLA valence circuits has been largely
unexplored. Here, I propose to uncover the dynamic interactions of BLA valence circuits to determine their
contribution to pain and hedonic affect, both locally within the BLA and at their long-range targets in the NAc.
During the mentored K99 phase, my career development and training will be supervised by my co-mentors,
Drs. Gregory Scherrer and Mark Schnitzer, with additional support from Drs. Robert Malenka, Sean Mackey,
and Brian Kobilka. To investigate the neural network mechanisms driving pain unpleasantness and comorbid
anhedonia, I will receive expert training in optogenetic-guided brain slice electrophysiology and time-lapse in
vivo Ca2+ imaging in freely behaving mice to uncover the functional interactions of neural ensembles encoding
nociceptive and appetitive sensory information throughout the development of chronic pain. During the
independent R00 phase, I will determine whether BLA valence circuits that differently innervate the NAc define
functionally and anatomically distinct “hedonic zones” within opioidergic circuits. I will further investigate the
relevance of these zones to behavior-selection and reinforcement during acute and chronic pain, and during
drug use conditions. The advanced training I will receive during this K99/R00 award will lay the foundations for
my future research program and NIH grant applications. This award will help me advance my own scientific
capabilities, and bolster my career as a successful, independent research scie...

## Key facts

- **NIH application ID:** 10144966
- **Project number:** 5R00DA043609-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Gregory Corder
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $245,872
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144966

## Citation

> US National Institutes of Health, RePORTER application 10144966, Deconstructing the network mechanisms of chronic pain and reward in the amygdala (5R00DA043609-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10144966. Licensed CC0.

---

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