# Harnessing cortical neuromodulation to disrupt pain perception

> **NIH NIH DP2** · UNIVERSITY OF PENNSYLVANIA · 2022 · $150,581

## Abstract

PROJECT SUMMARY
Chronic pain is characterized by sensory, emotional, and cognitive dysfunction. Some patients on opioid
therapies can perceive the negative valence of pain as separate, or “dissociated,” from the sensation of pain.
This suggests that altering the affective-attention dimension of pain contributes significantly to the therapeutic
effect of opioids. However, opioids have significant negative side effects. Opioids carry addictive and respiratory
depression liabilities due to the expression of mu opioid receptors (MORs)—the molecular receptor binding
opiates—in reward-related and brainstem breathing areas of the brain. Identifying the nociceptive brain circuits
underlying opioid analgesia, separate from those underlying dangerous side effects, is key to developing
improved, non-addictive therapeutics for managing chronic pain and combating the Opioid Epidemic.
Many brain regions contribute to the emotional and cognitive facets of pain. Importantly, anticipation of pain,
acute noxious stimuli, and chronic pain all strongly activate the anterior cingulate cortex (ACC). The function of
the ACC in pain processing appears to integrate nociceptive information within working memory to direct
attention to and facilitate anticipation of nociceptive stimuli, but it remains unknown how noxious information
enters the ACC. In the DP2 parent award, we are currently exploring nociceptive inputs from the amygdala,
however, there are other key connective routes of pain-related information into the ACC, such as the midline
thalamus (MTh). Here, we extend the parent DP2 studies to investigate the MOR+ MTh projection circuit that
innervates nociceptive ACC regions. In Goal 1, we will determine the neuroanatomy of opioidergic nociceptive
neural circuits using activity-dependent viral and mouse genetics, and in Goal 2 we will determine the functional
role of thalamocortical opioidergic circuits to pain behavior using cell-type specific manipulations and machine-
vision based behavior quantification methods, which were developed in the parent DP2 experiments. Completion
of the proposed research will facilitate the trainee’s technical mastery of several advanced neuroscience
technologies, data analysis and statistics, as well as several training goals to prepare the trainee for a career in
pain neurobiology research.

## Key facts

- **NIH application ID:** 10589454
- **Project number:** 3DP2GM140923-01S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Gregory Corder
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $150,581
- **Award type:** 3
- **Project period:** 2020-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10589454

## Citation

> US National Institutes of Health, RePORTER application 10589454, Harnessing cortical neuromodulation to disrupt pain perception (3DP2GM140923-01S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10589454. Licensed CC0.

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