# Dissecting motor cortex circuits underyling chronic pain relief

> **NIH NIH F32** · STANFORD UNIVERSITY · 2022 · $17,570

## Abstract

Project Abstract
More than 100 million Americans suffer from chronic pain. The choice to prescribe pain relief in the form of
opioids to people for long periods of time has been controversial due to the risk of addiction and reports of limited
efficacy to manage chronic nonmalignant pain (e.g., neuropathic pain). The heavy burden of chronic pain in
America prompts the need for alternative methods of non-addictive analgesia. One potential method of relieving
pain is through non-invasive electrical or magnetic stimulation of the brain. In human patients, the most effective
target of noninvasive stimulation is, surprisingly, the motor cortex. Motor cortex is best known for its role in
eliciting voluntary movements and has a somatotopic motor map with broad connections throughout the brain
and spinal cord, including understudied connections with the anterior cingulate cortex (ACC), mediodorsal
thalamus (MD), basolateral amygdala (BLA), and periaqueductal gray (PAG). These connections between motor
cortex and the regions known to be important for the affective component of pain may be the underlying circuits
that cause analgesia during motor cortex stimulation (MCS) of human patients suffering from chronic pain. To
fully dissect the mechanism of MCS, I propose to use a mouse model of chronic neuropathic pain. In Aim 1, I
will first identify the motor cortex neurons that respond when mice experience pain and further quantify their
downstream connections with pain regions like the ACC, MD, BLA, and PAG. In Aim 2, I will image the activity
of neurons in motor cortex during the development of chronic pain and during MCS-induced pain relief. In Aim
3, I will use optogenetic stimulation to selectively target MCS to subpopulations of neurons and determine which
are inducing analgesia. This resulting dataset will include activity patterns of nociceptive motor cortex neurons
and the cellular identity of their neuronal targets in other pain-relevant brain regions. This information will be
available for clinicians to optimize MCS treatment protocols to activate specific subpopulations and tuned to
neuronal activity patterns. This project will take place in the collaborative environment of Prof. Mark Schnitzer’s
(sponsor) lab at Stanford, an expert environment for innovative neuroscience and imaging techniques. Together
with the mentorship of leading pain neuroscientists, Profs. Greg Scherrer and Sean Mackey (co-sponsors), the
proposed training plan provides an excellent opportunity for me to combine new scientific ideas with cutting-edge
technology. I will gain valuable experience in using clinical treatments to ask scientific questions and create
useful experimental designs. This project will help to formulate me into an intendent scientist and position me to
start my own lab program studying pain circuitry and its intersect with motor circuits and behavioral outcomes.
Collectively, we will dissect the circuits underlying a currently effective, noninvasive trea...

## Key facts

- **NIH application ID:** 10401494
- **Project number:** 5F32DE030003-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Nicole Mercer Lindsay
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $17,570
- **Award type:** 5
- **Project period:** 2020-07-01 → 2022-09-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401494

## Citation

> US National Institutes of Health, RePORTER application 10401494, Dissecting motor cortex circuits underyling chronic pain relief (5F32DE030003-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10401494. Licensed CC0.

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