# Identification of Sex Differences in Monocytes and Metabolism in the Maintenance of Chronic Muscle Pain

> **NIH NIH K00** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $89,856

## Abstract

Project Summary
Fibromyalgia is a chronic musculoskeletal pain disorder that has a strong negative impact on quality of life and
is strongly biased towards women. There is a dire need for the development of targeted therapeutics as patients
are not responsive to current therapeutics. The significantly greater prevalence of chronic muscle pain in women
suggests female-biased mechanisms in the pathophysiology of its development and maintenance. Recent
literature on neuroimmune communication in chronic pain signaling have uncovered sexually divergent
mechanisms; however, there are little to no studies assessing how cellular metabolism in immune cells can
modulate pain processing. The research plan during the F99 phase of this proposal will test the specific
hypothesis that maintenance of chronic muscle pain is mediated by sex-specific differences in monocyte
activation and metabolism using a mouse model in which metabolism of monocytes is modulated by deletion of
liver kinase B1 (LKB1), a metabolic kinase. Anti-inflammatory functions are much more metabolically demanding
than pro-inflammatory functions, so these cells will have diminished anti-inflammatory activation. We anticipate
monocytes without LKB1 have a magnified pro-inflammatory phenotype during chronic muscle pain that is
maintained by distinct translational profiles in males and females. Assessment of pain behaviors, RNA
sequencing, flow cytometry, and cellular metabolism assays will allow for the identification of phenotypic changes
within peripheral monocytes driving the development and maintenance of chronic muscle pain. The work and
described in the F99 phase of this proposal will further our understanding of sexually dimorphic mechanisms of
immunometabolism as a driver of chronic muscle pain and provide direction for the development of targeted
therapeutics to reduce the impact of chronic muscle pain on patient quality of life. The focus of the K00 phase
will be to study immunometabolism and chronic pain in patients with fibromyalgia using neuroimaging and
expanding skillsets in immunology and computational biology. The ultimate goal of this proposal is preparation
for transition to a faculty position in neuroscience at a research institution as an independent translational
neuroimmunologist with a special focus on identification of sex-biased mechanisms in chronic muscle pain.

## Key facts

- **NIH application ID:** 10973685
- **Project number:** 8K00HD118378-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Melissa Elizabeth Lenert
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $89,856
- **Award type:** 8
- **Project period:** 2022-09-04 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10973685

## Citation

> US National Institutes of Health, RePORTER application 10973685, Identification of Sex Differences in Monocytes and Metabolism in the Maintenance of Chronic Muscle Pain (8K00HD118378-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10973685. Licensed CC0.

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