# Investigating the role of the microbiome and inflammation in acute and chronic pain in patients with sickle cell disease

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $748,758

## Abstract

PROJECT SUMMARY/ABSTRACT
The overall goals of the proposed work are to investigate the role of the microbiome and inflammation in acute
and chronic pain in patients with sickle cell disease (SCD). Intermittent, excruciating acute pain accounts for
the majority of emergency department visits and hospitalizations for patients with SCD and the frequency of
these episodes increase with age. Chronic, debilitating, daily pain also occurs in ~40% of adolescents and
adults with SCD and the incidence and severity of chronic pain also increases with age. A critical knowledge
gap exists in the identification of reasons other than chronic sickling that contribute to the unpredictable clinical
phenotype of frequent acute and chronic daily pain. Opioids are the backbone treatment for both acute and
chronic SCD pain; however they often provide ineffective analgesia and can lead to significant side effects and
stigma. An increased understanding of the biology of acute and chronic SCD pain is needed in order to
develop opioid-sparing, targeted therapies to improve the quality of life of patients with SCD. Alterations in the
intestinal microbiota or dysbiosis, a known driver of chronic inflammation, have not been explored in SCD but
play a role in other chronic inflammatory diseases and pain-related disorders. Dysbiosis has been associated
with pain in rheumatoid arthritis, migraines, chronic pelvic pain and chemotherapy-induced pain. Dysbiosis can
lead to a “leaky” intestinal barrier resulting in bacterial translocation into the blood. Bacterial translocation (i.e.,
systemic microbial antigen exposure) can trigger chronic inflammation which can sensitize peripheral pain
nociceptors and result in recurrent acute and chronic pain. Immune regulation of this inflammatory response
can modulate the inflammatory impact on pain. Nervous system sensitization occurs in SCD patients.
However, the biologic factors that lead to nervous system sensitization in SCD are unknown. Thus,
investigating the connection between the microbiome, inflammation and SCD pain is important. In this
proposal, we will investigate whether microbial antigens from intestinal microbiota alterations drive
inflammation and pain in patients with SCD. The following aims are proposed: 1) Examine the relationship
between systemic microbial antigen levels, intestinal microbiota composition and diversity and the systemic
inflammatory state in patients with SCD and healthy race-matched controls and 2) Investigate whether acute
and chronic pain in SCD patients is associated with increases in systemic microbial antigen exposure and an
elevated inflammatory state. Our collaborative and multidisciplinary team has clinical and research expertise in
SCD pain biology, inflammation, microbiome and SCD patient-reported outcomes. We will utilize a multifaceted
approach to investigate how microbial exposure and host inflammatory response impacts the expression of
SCD pain. Our work has the potential to identify targets...

## Key facts

- **NIH application ID:** 10000989
- **Project number:** 5R01HL142657-03
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Amanda M Brandow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $748,758
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000989

## Citation

> US National Institutes of Health, RePORTER application 10000989, Investigating the role of the microbiome and inflammation in acute and chronic pain in patients with sickle cell disease (5R01HL142657-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000989. Licensed CC0.

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