# Harnessing cortical neuromodulation to disrupt pain perception

> **NIH NIH DP2** · UNIVERSITY OF PENNSYLVANIA · 2020 · $2,436,375

## Abstract

PROJECT SUMMARY
Chronic pain is a major health crisis in the United States, affecting >100 million Americans and millions more
worldwide. In addition, the use of opioids to treat chronic pain has been a major driver in the opioid epidemic that
has swept over the country. Development of new classes of therapeutics that have a similar or higher efficacy
relative to opioids for treating pain but lack the addictive liability of prescription opioids could have profound
effects both for treating pain patients and for reducing the burden of the national opioid crisis. A significant barrier
in achieving this goal is that we have little understanding of the brain circuits and pathways that contribute to the
suffering caused by chronic pain. Our goal is to identify the neural circuit elements underlying pain affective
perception, decode how their neural computations evolve during chronic pain, and attempt to normalize these
pathological dynamics with precise circuit-based optical interventions. Here, we will achieve this goal by
visualizing critical opioid circuits within the neocortex using automated large-scale single-neuron resolution
imaging, optogenetic manipulations, and machine-vision behavior analysis. By achieving this goal, we will
generate new dynamic frameworks for modeling the emergence of chronic pain. These frameworks will inform
our translational targeting strategies using contemporary circuit disruption technologies with the ultimate goal of
promoting endogenous opioid peptide release only in the desired brain region, circuit, and synapses relevant to
pain processing, with temporal on-demand control. Therefore, successful implementation of our strategy could
unleash technologies for disrupting cortical and/or sub-cortical circuit-specific pathologies that alleviate the
suffering of chronic pain patients. The proposed research is well suited to the goals of the NIH New Innovator
Award program. The innovative combination of these technical and high-risk strategies has the potential to
transform our understanding of how chronic pain modulates brain networks and how to tightly-control them. Our
projects encompass a number of significant advances, both in concept and in techniques that might
fundamentally change the approach toward the rationale design of analgesics aimed at altering the neural circuits
underlying the negative affective perception of pain. My interdisciplinary background in pain neurobiology, opioid
pharmacology, and systems neuroscience, together with my demonstrated success in identifying the structure-
function logic of neural circuits is the precise combination of skills that make me well suited to fully execute a
project of this ambition. The NIH Director’s New Innovator Award would provide an invaluable jumpstart to my
early career and support the continued trajectory of my research program into deconstructing the brain’s pain
systems for the development of non-traditional strategies to treat the unpleasant affect and suf...

## Key facts

- **NIH application ID:** 10002810
- **Project number:** 1DP2GM140923-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Gregory Corder
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,436,375
- **Award type:** 1
- **Project period:** 2020-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002810

## Citation

> US National Institutes of Health, RePORTER application 10002810, Harnessing cortical neuromodulation to disrupt pain perception (1DP2GM140923-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10002810. Licensed CC0.

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