# Identifying non-opioid strategies to manage oral cancer pain

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $250,000

## Abstract

PROJECT SUMMARY
An almost universal symptom of head and neck squamous cell carcinoma (HNC) is cancer-related pain. Oral
cavity and oropharyngeal cancers are even more painful than the rest of the head and neck anatomic sites.
HNC-associated pain frequently develops resistance to morphine and few strategies are available for effective
pain management after they develop resistance. In addition, the inevitable morphine dose escalation leads to
constipation, nausea, sedation, dry mouth, and myoclonus, which substantially decrease the patient’s quality of
life. Recent studies have also shown that morphine has undesirable immunosuppressive features. Through the
support of the parent R01 award, we have found that type-I interferon signatures underpin the immunogenicity
of HNC and made seminal contributions to the understanding of oncogenic suppression of type-I interferons by
promoting the rapid turnover of an adaptor protein, stimulator of interferon genes (STING). In addition to the
potential of STING agonists in reprograming the antigen-presenting cells to cross prime CD8+ cytotoxic T-
lymphocytes more effectively, we recently uncovered an unexpected yet powerful function of STING agonists
in promoting analgesia. Hosts that are deficient in the STING-type-I interferon pathway show significantly
elevated nociceptor excitability. We have found that common driver oncogenes for HNC initiation suppress
STING and lead to type-I interferon deprivation in the tumor microenvironment. In this supplement proposal,
we will provide transformative evidence to leverage type-I interferons for the management of HNC-associated,
morphine-resistant pain. To achieve this goal, we have generated novel and rigorous HNC models with high
fidelity resemblance to human HNC mutational features. We will integrate comprehensive modeling, behavior
studies, and single-cell technologies to identify non-opioid agents for HNC pain management.

## Key facts

- **NIH application ID:** 10617001
- **Project number:** 3R01DE026728-05S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Christopher Ryan Donnelly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $250,000
- **Award type:** 3
- **Project period:** 2022-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10617001

## Citation

> US National Institutes of Health, RePORTER application 10617001, Identifying non-opioid strategies to manage oral cancer pain (3R01DE026728-05S1). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10617001. Licensed CC0.

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