One of the most data-dense biospecimen repositories in the world is currently being developed at the University of Florida, which could transform the way chronic pain is studied and treated.
UF scientists are asking the question: Why do people experience pain differently? The answer may be found in a surprising place: valuable human tissue that would otherwise be thrown away after surgery.
With $10 million in funding from the National Institutes of Health, researchers from UF’s Herbert Wertheim College of Engineering and the College of Dentistry are storing post-surgical human tissue in a repository, collecting data points from the samples, and mapping and analyzing the tissue via artificial intelligence tools. The goal is to explore pain pathways and create custom pain treatments.
“Pain is often viewed as something simple – a lot of pain, a little pain,” said Kyle Allen, Ph.D., a professor in UF’s J. Crayton Pruitt Family Department of Biomedical Engineering. “How do I know you experience pain the way I experience pain? We don’t experience it the same way, and we know this through a lot of research.”
Allen is working alongside Yenisel Cruz-Almeida, Ph.D., the associate director of the Pain Research & Intervention Center of Excellence in UF’s College of Dentistry, to conduct clinical research with patients before their knee and temporomandibular joint (TMJ) replacement procedures.
“How do I know you experience pain the way I experience pain? We don’t experience it the same way, and we know this through a lot of research.”
Kyle Allen, Ph.D., professor, J. Crayton Pruitt Family Department of Biomedical Engineering
During the procedures, surgeons remove small amounts of tissue, which Cruz-Almeida and Allen then analyze. The researchers input thousands of data points gleaned from the tissue and pre-surgical interviews, map them with AI, and analyze them for patterns that could predict response to pain treatments.
“These patients come into orthopedics looking for a knee replacement or come into dentistry looking for a TMJ replacement,” Allen said. “If the patient enrolls in our study, they spend almost a full day in Yenisel’s lab giving information on everything about their pain experience.”
Collecting the samples
So far, a total of 2,400 samples have been collected from 24 patients, most of whom have undergone knee replacement surgeries.
“These individuals are having surgery, so we are going in and collecting their tissue that is normally thrown away. That is how this got started,” Cruz-Almeida said, adding that the idea for the project arose in 2020. “I always asked, ‘Can we study that tissue? Can we do some of the basic science stuff that Kyle does to his animals?’”
Allen’s research on rats has been instrumental in this interdisciplinary project. Using the collected human tissue samples, Allen and Cruz-Almeida have translated pain data to map the same points in rats and then translated that back to pain patterns in humans. That translational perspective starts in the human to see what is happening in the physiology.
“Everybody thinks it’s rodent-to-human, but it’s not,” Allen said. “If we’re not seeing that signal in the human, then you’re just curing rodents.”
Cruz-Almeida added, “Kyle is modeling this in the animals but really trying to compare it with getting tissue from the humans and their phenotypes, which is what I do in my lab. What is their behavior and how do they report pain?”
Allen and Cruz-Almeida are exploring how the neurons – the nerve cells – actually sense pain.
“We must comprehensively figure out if they are pain nerves,” Cruz-Almeida said. “Are they tactile? It’s complex, but they’ve been doing it forever in basic science. Basically, our goal now is working together and let’s do something in humans.”
Examining the results
In the clinical screenings, the researchers collect about 2,000 data points from the patients. Then the researchers generate thousands, often even millions, of data points from the biological samples.
“One sample can be used to analyze multiple things. What we’re looking at are the nerve maps and how the nerves are specifically changing,” Allen said. “Since we are going through the process of collecting all this tissue, we’re saving all of it, so if anybody wants to come back and say, ‘Oh, you have that nerve signature, does that relate to some genetic marker? Does that relate to some other factor?,’ they can.”
Additionally, the researchers photo-document the dissection procedure to know exactly where the samples originated.
While the patients may be able to describe their pain, Cruz-Almeida said, “that is not the complete picture. It’s their behavior. The way they move differently will provide insights into what may be causing or driving the pain.”
For the success of the project, Allen and Cruz-Almeida also credit Roger Fillingim, Ph.D., professor and director of the Pain Research and Intervention Center of Excellence; Robert Caudle, Ph.D.; UF Health orthopedic surgeons Simon Mears and Hernan Prieto of UF’s Orthopedics and Sports Medicine Institute; and UF Dentistry surgeon Frank Dolwick, D.M.D., Ph.D.
“This team is bringing together quantitative pain data with the most advanced biological assays in human and preclinical samples. One of the most data-dense pain repositories in the world is being created here at UF, combining biological, neurological, psychological, and societal determinants of a person’s pain state,” said Cherie Stabler, Ph.D., chair of the J. Crayton Pruitt Family Department of Biomedical Engineering. “Importantly, this data will be minable using emerging artificial intelligence techniques.”
And, “since the revolution of AI is coming,” Allen said, “the goal here is to generate data, data, data.”