# Transcriptomics of Pain in Sickle Cell Disease

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $396,200

## Abstract

PROJECT SUMMARY/ABSTRACT
Patients with sickle cell disease (SCD) exhibit marked inter-individual heterogeneity in frequency
of acute pain events, or vaso-occlusive crises (VOC) and development of chronic pain. The nidus
of a VOC is typically the adhesion of a leukocyte to the endothelium, bringing with it a red cell
which deoxygenates and sickles, resulting in vaso-occlusion, ischemia, and pain. We therefore
collected SCD patient RNA from CD71+ cells (red cell precursors that still retain RNA) and
CD45+, leukocytes from individuals with and without chronic pain, and longitudinal collections
obtained at steady state, in VOC, and VOC resolution, and submitted these samples to TOPMed
for RNASeq analysis. We propose to leverage this transcriptome data from a well phenotyped
pediatric SCD cohort to address the unmet need of objective, quantifiable markers of acute and
chronic pain, and evaluate in the context of the germline and somatic mutations found in the same
subjects’ whole genome sequencing (WGS) data, also in TOPMed. Short term goals are to 1)
identify genes and pathways altered in the chronic pain state, 2) identify transcriptome changes
associated with pain events and their resolution, 3) generate a transcriptional risk score for the
development of chronic pain, and 4) determine which variants associated with chronic pain
development are likely to be causative through transcriptome wide association studies. Long
term goals are to use these findings to 1) develop targeted therapies to prevent and treat VOC,
2) therapies to treat chronic pain in SCD, and 3) biomarkers to distinguish acute pain events from
chronic pain. The ability to do so will allow providers to manage VOC appropriately and
aggressively, without inadvertently confusing chronic pain with an acute pain episode. Our
inability to distinguish between acute and chronic pain harms our patients, as the opioids that are
the mainstay for VOC treatment often worsen chronic pain through opioid induced hyperalgesia.
Our work will leverage TOPMed samples via our innovative transcriptomics analysis to identify
risk factors, therapeutic targets, and biomarkers of chronic pain, in order to improve the care and
quality of life of individuals living with SCD.

## Key facts

- **NIH application ID:** 10501596
- **Project number:** 1R01HL164583-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Vivien Andrea Sheehan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $396,200
- **Award type:** 1
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501596

## Citation

> US National Institutes of Health, RePORTER application 10501596, Transcriptomics of Pain in Sickle Cell Disease (1R01HL164583-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10501596. Licensed CC0.

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