# Functional consequences of sensory neuronal invasion in oral cancer pain and carcinogenesis

> **NIH NIH R00** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $249,000

## Abstract

PROJECT SUMMARY
 Oral cancer pain results from activation of primary afferent neurons by cancer-secreted mediators. My
previous work demonstrated that mice bearing tongue cancers induced by 4-nitroquinoline-1-oxide (4NQO)-
carcinogenesis exhibit nociceptive behavior and trigeminal ganglia neurons (TGNs) innervating the tongue
become hyperexcitable. Oral cancer cells also secrete neurotrophic factors that induce neuronal sprouting into
the cancer, while local neurotransmitter release from TGNs innervating the cancer has been linked to
carcinogenesis. I hypothesize that oral cancer and sensory neurons interact, such that, oral cancer
induces sensitization, sprouting and plasticity in neurons, and efferent neuronal activity promotes oral
carcinogenesis. In support of my hypothesis, I demonstrated, using an oral cancer xenograft model that nerve
axotomy suppressed oral squamous cell carcinoma growth in the hindpaw. To test my hypothesis and to
prepare me for an independent research career, I propose in the K99 phase to gain skills in high-resolution
microscopy, quantitative analysis, cancer cell biology and oral histopathology. Specifically, I will characterize
the type, distribution, sprouting features and development over time of sensory nerves innervating the oral
cancer microenvironment during 4NQO-carcinogenesis (Aim 1). In Aim 2, I will determine the reciprocal
impact of neuron-cancer communication using cell cultures in vitro. I propose to use these skills in the R00, to
study the differential impact of primary afferent neurons on oral cancer pain and carcinogenesis through
inhibition of cancer-induced neuronal sprouting and ablation of TGN subpopulations in an oral cancer mouse
model. The successful completion of the proposed experiments and training program will further my knowledge
in the relationship between sensory neurons and cancer, as well as develop skills I need to pursue an
independent research career.

## Key facts

- **NIH application ID:** 10200764
- **Project number:** 5R00DE028019-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Nicole N Scheff
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200764

## Citation

> US National Institutes of Health, RePORTER application 10200764, Functional consequences of sensory neuronal invasion in oral cancer pain and carcinogenesis (5R00DE028019-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200764. Licensed CC0.

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