# Molecular mechanism and targeting of chronic pain in sickle cell disease

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $661,398

## Abstract

Our long-term goal is to advance the knowledge of the neurobiological and molecular mechanisms underlying
chronic pain in sickle cell disease (SCD) and develop effective pharmacologic treatments. Pain is not only a
life-long companion but also a predictor of mortality for the 100,000 Americans living with SCD, people mainly
of African or Latin descent.1-3 Pain and SCD are so intimately intertwined, that African tribal words for the
disease, spoken hundreds of years before Herrick described SCD in the western literature, are onomatopoeic
for pain. Though it is now appreciated that SCD pain is characterized by chronic pain with episodes of acute
pain,4-5 the neurobiology of chronic pain is poorly studied, not well characterized, and is refractory to currently
available therapies,6-7 a century after Herrick's seminal paper.8 A great deal of research has been carried on
the disease itself.9-10 Several transgenic models of SCD have been developed, including the humanized
Berkeley (BERK)11 and Townes' sickle cell transgenic mice (TOW),12 both representing SCD phenotypes that
closely mimics many features of severe SCD in humans.13-20 We propose to employ these well-characterized
sickle cell transgenic mouse models for studying molecular and epigenetic mechanisms underlying chronic
pain, which can hold much promise for a more thorough understanding of pain mechanisms in SCD and may
guide development of effective therapies. This R35 program will advance the knowledge of molecular
mechanisms underlying chronic pain in SCD and apply new knowledge to design and examine experimental
therapeutics in mouse models of SCD. The program is designed to have flexibility that expanded or new
research directions can be rapidly taken when new findings or emerging technology become available. Our
research applies the power of molecular and cellular biology, pharmacology, neurobiology, epigenetics,
targeted delivery, and other cutting-edge tools and we have existing research, expertise and research facility
for studying sickle pain problem at molecular, cellular, and systems levels. This program will methodologically
investigate chronic pain in SCD using several newly developed innovations and start to fill the void in our
understanding of chronic pain of SCD. Having identified the CaMKIIα target for SC pain and recently moved a
CaMKIIα inhibitor from bench to a Phase I study in patients with SCD, our team is uniquely suited to carry out
research in this R35 program. Our innovation has a high probability of success given our outstanding track
record, vibrant ongoing research program, and the designed flexibility in pursuing new research directions.

## Key facts

- **NIH application ID:** 10319980
- **Project number:** 5R35HL140031-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Zaijie Jim Wang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $661,398
- **Award type:** 5
- **Project period:** 2018-01-16 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319980

## Citation

> US National Institutes of Health, RePORTER application 10319980, Molecular mechanism and targeting of chronic pain in sickle cell disease (5R35HL140031-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10319980. Licensed CC0.

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