# The Role of Peripheral Brain-Derived Neurotrophic Factor (BDNF) Signaling in Oral Cancer Pain

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $362,188

## Abstract

Project Summary
Numerous studies have indicated that pain is the top ranked symptom in head and neck cancer (HNC)
patients. However, available treatments are limited and associated with severe side effects adding
substantially to the burden of having cancer. Thus, there is a critical need for novel analgesics. However, there
is a large gap in knowledge for oral cancer pain mechanisms and thus pain control is often incomplete.
Because pain in oral cancer occurs even before a tumor becomes clinically apparent, this cardinal symptom
indicates that cancer cells control the activities of surrounding nociceptors at the site of the tumor. The
objective here is to study a novel mechanism for oral cancer pain by which tumor cells interact with sensory
neurons at the orthotopic site. Our central hypothesis is that Brain-derived neurotrophic factor (BDNF) is
released from oral squamous cell carcinoma (OSCC) cells and activates adjacent sensory fibers, contributing
to OSCC-induced pain. This hypothesis is based on compelling preliminary data demonstrating that BDNF
levels are elevated in oral tumor in mice and that antagonizing the BDNF receptor reverses pain-like behaviors
in vivo. We will employ behavioral, biochemical, anatomical methods as well as electrophysiological analysis of
lingual nerve fibers that allows studying tumor-nerve interactions in situ, to study the aims:
Aim 1: Determine whether OSCC-released BDNF contributes to oral cancer pain. Using superfusion
techniques, electrophysiology and behavioral assays, this aim will determine the release of BDNF from tongue
tumor as well as test whether released BDNF regulate surrounding nerve fibers activities in the tongue and
produce pain-like behaviors in vivo. Results from male and female mice will be compared to determine BDNF-
induced sexually dimorphic effects.
Aim 2: Determine whether TrkB and p75 receptors (p75R) play a role in BDNF mediated peripheral oral cancer
pain. The effects of pharmacological and molecular inhibition on the TrkB and p75 receptors in sensory
neurons will be determined with electrophysiologic recordings. Follow-up experiments will test the effect of
application of recombinant human BDNF on sensory fiber activities in naïve animals. Sex-dependent
differences will also be determined.
Aim 3: Determine downstream BDNF signaling pathways in mediating oral cancer pain. Using male and
female mice, this aim will employ anatomical and electrophysiological methods to identify the downstream
pathways of TrkB and the p75 receptor that may play a role in BDNF-induced oral cancer pain.
 Collectively, experiments proposed herein provide critical and comprehensive tests of the central
hypothesis. The translational significance of this project is strengthened by the use of human cancer cells and
a clinically relevant orthotopic model that mimics patient symptoms as well as the novel electrophysiology
method to study tumor-nerve interaction at the very site of tumor development.
RELEVANCE: ...

## Key facts

- **NIH application ID:** 9978011
- **Project number:** 5R01DE027223-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Shivani B Ruparel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $362,188
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978011

## Citation

> US National Institutes of Health, RePORTER application 9978011, The Role of Peripheral Brain-Derived Neurotrophic Factor (BDNF) Signaling in Oral Cancer Pain (5R01DE027223-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9978011. Licensed CC0.

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