Bringing sickle cell disease pain into focus

Pain is a constant, complex companion that clinicians often struggle to understand and measure for people living with sickle cell disease. Traditional pain scales reduce this deeply personal experience to a single number that is often inaccurate. A new study led by Carnegie Mellon University’s Wood Neuro Research Group in new window takes a more human-centered approach, using advanced brain imaging and a digital visualization tool to illuminate how pain is processed in the brain, aiming to bridge the gap in pain interpretation between patients and clinicians.

“Traditional questionnaires only scratch the surface,” explained Joel Disu, first author of The Journal of Pain in new window paper and biomedical engineering in new window Ph.D. student. “They don’t capture the complexity or the internal experience of sickle cell pain. We wanted to see what happens in the brain when people describe their pain in a way that’s truer to how they actually feel it.”

The team explored how Painimation, a novel app developed by Emory University collaborator Dr. Charles Jonassaint, could help decode the neural signatures of pain in adults with sickle cell disease. Instead of rating pain on a 1-to-10 scale, participants use animated visuals to describe what their pain feels like, for example throbbing, stabbing, cramping, or shooting sensations.

Using ultra-high-resolution MRI data, the researchers compared brain connectivity patterns between 27 patients with sickle cell disease and 30 healthy, pain-free participants. They focused on three key brain networks linked to pain perception: the default mode, salience, and somatosensory networks. Their results showed that patients with sickle cell disease had significantly reduced connectivity across all three, particularly in regions involved in emotion, attention, and sensory processing.

When the team linked these imaging findings to participants’ Painimation selections, a striking pattern emerged. Pain descriptors like cramping and stabbing correlated strongly with changes in the somatosensory network, the area responsible for processing physical sensations like touch and pressure. Moreover, patients who rated these sensations as more intense showed even greater disruption in those brain regions.

“This gives us a foundational step toward developing objective pain biomarkers,” Disu explained. “We can begin to see, in real time, how the quality and intensity of pain map onto the brain.”

Beyond its scientific novelty, the study addresses a critical gap in healthcare communication. Pain in sickle cell disease is frequently misunderstood, leading to mistrust between patients and providers. Many patients report managing their pain crises at home, because they fear being dismissed, the increased burden of healthcare fees, or being labeled as drug-seeking when they seek care.

“Our work helps visualize what has long been invisible or ignored,” noted Sossena Wood, assistant professor of biomedical engineering at Carnegie Mellon. “This research validates patients’ experiences with neuroscientific evidence. It shows that the pain they feel is real, measurable, and rooted in brain function in vital pain receptors.”

The implications extend beyond research labs and translate to an assessable digital tool that can be assessed in the patient’s home. Painimation is already being adopted by several sickle cell communities across the country, helping clinicians better interpret pain experiences. Wood’s team hopes to build on these findings by exploring how tools like virtual reality and wearable sensors might one day help modulate pain perception or even reduce it through targeted brain stimulation.

Earlier this year, Disu was selected by the American Society of Hematology to receive the 2025 Hematology Inclusion Pathway Graduate Student Award. The honor includes a $40,000 annual stipend over two years to support his ongoing research, including studies like this one that aim to transform the way pain is understood and managed in sickle cell disease. Disu is the first Carnegie Mellon student to receive this prestigious award.

Wood added, “Ultimately, we want to bridge the gap between patients’ lived experiences and what clinicians can measure. By bringing together neuroscience and empathy, we can start to transform the way pain is understood and treated in sickle cell disease.”

This research was funded in part by the National Institutes of Health and Patient-Centered Outcomes Research Institute.

For media inquiries, please contact Sara Pecchia at pecchia@cmu.edu.