# Targeting a novel neural circuit to modulate trigeminal neuropathic pain

> **NIH NIH R03** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2022 · $151,500

## Abstract

Project Summary:
 Trigeminal neuropathic pain is a debilitating condition and represents a challenge to clinicians because
such pain is often refractory to currently available therapies. The brain neural circuit mechanism underlying this
type of pain remains poorly understood. We will address the knowledge gap in this project. The objective of this
project is to dissect a novel neural circuit for the modulation of trigeminal neuropathic pain. In my preliminary
study, using a revolutionary approach called “Targeted Recombination in Active Populations (TRAP)”, I identify
that neurons in the anterior paraventricular thalamic nucleus (aPVT) are markedly activated by chronic
constriction injury of the infraorbital nerve (CCI-ION). By anterograde and retrograde viral tracing, I show that
the TRAPed aPVT neurons directly project to anterior cingulate cortex (ACC). Moreover, I found that optogenetic
excitation of the TRAPed aPVT neurons enhances CCI-ION-induced trigeminal neuropathic pain and
optogenetic silencing of the aPVT neurons attenuates such pain. My preliminary results suggest that aPVT
neurons and their projection to ACC could be involved in the modulation of trigeminal neuropathic pain. In this
project, I will further interrogate the role of aPVT-ACC pathway in trigeminal pain modulation. My hypothesis is
that specific manipulation of aPVT-ACC pathway can modulate trigeminal neuropathic pain in an activity-
dependent manner: Specific activation of aPVT-ACC pathway enhances trigeminal neuropathic pain through
increasing neuronal activity in the ACC; oppositely, specific inhibition of aPVT-ACC pathway produces pain relief
by decreasing neuronal activity in the ACC. To address this central hypothesis, I will use multidisciplinary
approaches to conduct the following studies in two specific aims. In Aim 1, I will determine the role of aPVT-ACC
pathway in trigeminal pain modulation by investigating the effect of optogenetic manipulation of this pathway on
CCI-ION-induced trigeminal neuropathic pain. Both evoked and spontaneous pain behaviors will be measured
with von Frey test and real-time place preference assay, respectively. In Aim 2, I will characterize aPVT-ACC
pathway-mediated regulation of neuronal activity in the ACC during trigeminal neuropathic pain using miniatured
microscope-based in vivo calcium imaging in freely moving mice. Collectively, I expect to show that the aPVT-
ACC pathway is critical for trigeminal pain modulation. The proposed research is significant since it will advance
our understanding of brain neural circuitry for pain modulation. The proposed studies are innovative since these
studies will reveal a previously unrecognized neural circuit that underlies trigeminal pain modulation.

## Key facts

- **NIH application ID:** 10588645
- **Project number:** 1R03DE031822-01A1
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** SUFANG LIU
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $151,500
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10588645

## Citation

> US National Institutes of Health, RePORTER application 10588645, Targeting a novel neural circuit to modulate trigeminal neuropathic pain (1R03DE031822-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10588645. Licensed CC0.

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