Kate Sadler, PhD

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I use mouse models of sickle cell disease to study the neurobiological basis of acute and chronic pain.

Sickle cell disease (SCD) is the most common genetic blood disorder in the world. Approximately 100,000 Americans, primarily those of African descent, suffer from this condition that is named for the rigid shape that red blood cells take in affected individuals. Pain is one of the primary symptoms of SCD and the leading reason that patients with this condition seek medical attention. Patients with SCD experience many types of pain throughout their life; excruciating acute pain episodes often begin following the fetal-to-adult hemoglobin switch that occurs during late infancy, and chronic pain develops in many patients as they age.

The biological basis of both acute and chronic SCD pain is unclear. In my research program, I use transgenic mouse models of SCD to investigate how SCD pain is processed by the peripheral and central nervous system. Findings observed in this naturally developing, bonafide chronic pain model are often reexamined in other models to determine broad translational potential. Specific areas of interest are discussed below.

How does the gut microbiome contribute to chronic pain?

The human gastrointestinal tract is inhabited by millions of bacteria that are critical for normal gut function. Over the past decade, accumulating evidence has suggested that these bacterial populations (collectively known as the gut microbiome) are disrupted in many neurological conditions including mood disorders, autism, schizophrenia, and chronic pain. It is unclear if disease-related changes in bacteria drive symptoms in patients, or if microbial changes are merely a result of the underlying condition. Using fecal material transplant experiments, I am directly investigating if and how the gut microbiome from various chronic pain models modulates sensory signaling in the peripheral and central nervous system. These experiments will increase our understanding of interoceptive processes and provide numerous opportunities for novel drug development.

Illustration by Teresa Patitucci, PhD

Funded by NHLBI K99/R00 Career Transition Award

How is sickle cell pain processed in the brain?

Very little is known about how sickle cell disease pain is encoded within the central nervous system. A recent review identified only 4 brain imaging studies completed in patients with SCD, and only 3 papers have used transgenic mice to understand how the brain is involved in SCD pain. This lack of data is not due to lack of reason; accumulating evidence supports that disease-related neurological changes in the central nervous system, and not just disease-related stroke or cerebral infarct drive sickle cell disease pain. Central sensitization is observed in patients with sickle cell and correlated with pain intensity and frequency. Chronic sickle cell disease pain is also exacerbated by co-morbid mood disorders including clinical depression and anxiety. I am investigating how the amygdala, a brain region traditionally associated with emotional processing, encodes acute and chronic sickle cell disease pain. Understanding how mood and pain information are simultaneously processed in this region will hopefully identify targets or strategies for lessening both disruptive symptoms in individuals with sickle cell disease.