# Sympathetic modulation of head and neck cancer pain

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $370,073

## Abstract

PROJECT SUMMARY
The majority of patients with head and neck squamous cell carcinoma (HNSCC) present with severe pain and
increased stress which exceeds the levels seen in other cancers. Due to a multitude of factors, including
amplificition of standard therapies, HNSCC patients are now living longer with the effects of their cancer and its
treatment. The presence of pretreatment pain has been identified as a prognostic indicator of poor survival.
The prognostic and long-term effects of cancer stress are unknown. Preliminary data using preclinical mouse
models support of the efficacy of beta-adrenergic antagonism using beta-blockers in the treatment of cancer-
related pain and progression; we found a reduction in orofacial nociceptive behavior and tumor size in cancer-
bearing mice treated with propranolol in their drinking water. In addition, cancer-secreted mediators increased
the adrenergic receptor signaling in trigeminal tongue primary afferent neurons as measured by norepinephrine
evoked calcium transients. The hypothesis of this proposal is that sympathetic nervous system exacerbates
cancer pain and drives tumor progression via local adrenergic signaling in the cancer microenvironment. To
test this hypothesis, we will explore the relationship between patient-reported pain, psychological symptom
burden (i.e., anxiety, depression, social support), and circulating catecholamine levels in HNSCC patients prior
to treatment and through survivorship. We seek to determine if low pre-treatment pain and psychological
symptom burden will predeict better patient reported outcomes during survivorship. Using preclinical mouse
models of oral cancer, we will investigate the impact of cancer-mediated sensitization on adrenergic signaling
in trigeminal primary afferent neurons innervating the tongue in vitro as well as the functional impact of stress
on cancer pain behavior and associated peripheral nerve plasticity in vivo. In order to improve outcomes in
HNSCC survivors, there is an urgency to better understand the prevelance of pain and stress in HNSCC
patients, as well as the underlying biological mechanisms.

## Key facts

- **NIH application ID:** 10877136
- **Project number:** 5R01DE030892-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Nicole N Scheff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $370,073
- **Award type:** 5
- **Project period:** 2021-07-06 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877136

## Citation

> US National Institutes of Health, RePORTER application 10877136, Sympathetic modulation of head and neck cancer pain (5R01DE030892-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10877136. Licensed CC0.

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