# Omics of Pain in the Context of Declining Estrogen

> **NIH NIH K99** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $94,770

## Abstract

PROJECT SUMMARY/ABSTRACT
 Chronic musculoskeletal pain (MSKP) is a significant problem in many women with hormone receptor-
positive early stage breast cancer receiving treatment designed to prevent cancer recurrence by blocking
estrogen production via systemic inhibition of the aromatase enzyme. MSKP interferes with functional status,
adherence to therapy, and increases utilization of health care resources. Unfortunately, very little is known
about the molecular mechanisms underlying MSKP related to a decline in estrogen in women with breast
cancer. Evidence supports that dysregulation of adrenergic function is present in women with MSKP. In fact,
both β-antagonists and α2-agonists have been investigated as treatment for MSKP pain disorders, and
evidence from our group as well as others support a role for pain inhibition via α1-antagonists. The purpose of
this K99R00 proposal is to provide the applicant with the necessary training and research experience to
examine the dynamic RNA transcriptome and DNA methylome to identify genes and biological pathways that
are involved in development of cancer pain. The purpose of the proposed K99 study is to generate knowledge
about MSKP development within the context of declining estrogen in women with breast cancer. The K99
phase of this project capitalizes on data and blood samples generated through an ongoing project that recruits
postmenopausal women newly diagnosed with early stage breast cancer who will receive aromatase inhibitor
therapy (R01CA196762, the EPICC study). The K99 also benefits from an ongoing project generating DNA
methylation data from blood samples of the women in the EPICC study (R01CA221882). The specific research
aims for the K99 study are to (1) test the hypothesis that 6 months of decreased estrogen leads to changes in
gene expression and this is related to changes in the pain phenotype in women with breast cancer; and (2) test
the hypothesis that 6 months of decreased estrogen leads to changes in DNA methylation and this is related to
changes in the pain phenotype in women with breast cancer. The K99 training plan leverages the superb
research-intensive environment and resources at the University of Pittsburgh to ensure the applicant’s
development of (a) proficiency in omics (particularly transcriptomics and epigenomics), (b) competency in
analysis and bioinformatics of omics data, (c) proficiency in pain mechanisms, and (d) knowledge and skills for
professional career development. The specific aims of the R00 study are to (1) identify changes in the
regulation of genes that are associated with variability in cancer pain based on cancer type; (2) identify
changes in the regulation of genes that are associated with variability in cancer pain based on cancer therapy;
and (3) explore the potential mediating and moderating effects of sex on the relationship between gene
regulation and pain. This research generates the knowledge needed to develop a research program focusing
on develop...

## Key facts

- **NIH application ID:** 9951374
- **Project number:** 1K99NR019080-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Monica Ann Wagner
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $94,770
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9951374

## Citation

> US National Institutes of Health, RePORTER application 9951374, Omics of Pain in the Context of Declining Estrogen (1K99NR019080-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9951374. Licensed CC0.

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