The touch of a feather, the itch of a mosquito bite, the prick of a needle: The body is capable of distinguishing and responding to all of these sensations in a near instantaneous relay, from skin to brain and back again.
“Our brain is constantly computing these things, and in healthy people it never gets it wrong,” says Ishmail Abdus-Saboor, a biologist in Penn’s School of Arts and Sciences.
The details that drive these processes are now at the heart of Abdus-Saboor’s research. Using a variety of techniques and models, he and his lab—established at Penn last year—seek to tease out the nervous system pathways involved in translating sensations to the brain, with a particular focus on acute and chronic pain.
His work has taken on a new significance in light of the opioid epidemic.
“As a field we have really struggled in identifying novel pain killers,” he says. “This is why we have an overreliance on opioids.”
Getting to the bottom of basic mechanisms in pain sensation has the potential to uncover new pathways that could be targeted with alternative medications. And with a new technique for applying a measurement to pain itself, Abdus-Saboor has in hand a platform that could be used to screen new drugs or even help clinicians one day evaluate their patients’ discomfort in a much more rigorous way than is currently available.
Animal behavior and biology got their hooks into Abdus-Saboor when he was a child. Growing up in Philadelphia’s Germantown neighborhood, he fashioned a laboratory in his home at age 14, winning a citywide science competition for his investigations of crayfish.
He carried that fascination with him through his undergrad years at North Carolina A&T State University, pursuing animal science as a pre-vet student. A summer in a laboratory at Penn refined that interest. The mysteries contained in the molecules and genes of animals began to emerge as the most captivating to Abdus-Saboor.
He wound up pursuing his graduate studies with Meera Sundaram at Penn in the Perelman School of Medicine, focusing on the genetics of the nematode worm Caenorhabditis elegans. But he made a conscious choice to shift gears as he embarked on two postdoctoral fellowships.
“Thinking about running my own lab one day, I was considering which area has the biggest growth potential in biomedical research,” he recalls. “The brain is the last frontier; it’s the least well-understood organ. I thought that, if I could apply some of the tools that I’d been learning in genetics and molecular biology toward the study of the nervous system, then perhaps I could make some important discoveries and look at things from a different vantage point.”
First in a postdoctoral fellowship with Benjamin Shykind of Cornell University and in a second position working with Wenqin Luo back at Penn, Abdus-Saboor played catch up in the field of neuroscience.
“Basically, every single approach that I worked on was new to me,” he says. “But I think that naïveté helped me.”
Specifically, Abdus-Saboor started asking questions about the common techniques use to evaluate responses to sensory stimuli in mouse studies and wasn’t satisfied with the answers. Certain assays, for example, relied on a binary response—either the animals responded to a stimulus or they didn’t—a measure that struck Abdus-Saboor as “rather crude and possibly biased.”
Over the last few years, as he wrapped up his postdoc with Luo and established his own lab at Penn, he set out to create a more refined scale for evaluating these types of responses. His technique relies on the use of a high-speed videography, capable of capturing 1,000 frames per second. In a paper published in August in Cell Reports, he, colleague Nathan Fried, Luo, and others reported the creation of a nuanced mouse pain scale that could effectively differentiate responses to a variety of sensory stimuli.
“Taking lessons from other model systems, mainly fruit flies and zebrafish, people have been using high-speed cameras to slow down behaviors that we can’t see with the naked eye,” says Abdus-Saboor. “I had the hypothesis that if we did this, maybe there was a lot more information we could extract that could inform us and teach us about what the animal is experiencing. And that turned out to be the case.”
Processing frames from these recordings manually, which is how the researchers initially completed the study, was a tedious task. But working with biostatisticians, computational biologists, and machine-learning specialists, Abdus-Saboor and members of his lab were able to streamline the process, and, in collaboration with departmental colleague Joshua Plotkin, are working to automate the video frame-by-frame analysis.
“We want others to easily adopt this technology, and automation would help avoid the potential error and variability of human scoring,” he says. “There are emerging technologies that are allowing us to do this.”
So far, they’ve tested the platform using both male and female mice representing a variety genetic types and have gotten consistent results across the board.
As his lab has developed this technology, they’ve been working in parallel to more deeply understand the nervous system circuits that produce the sensation of pain, especially in the context of chronic pain. People who suffer from chronic pain become more sensitive to various types of touch, even an otherwise innocuous application of warmth or pressure.
“This is the chronic pain we hear a lot about now, in this opioid epidemic era,” Abdus-Saboor says.
In his relatively short time as a faculty member, he’s already struck up collaborations with researchers working on pain elsewhere in the University to advance the science of treating pain. In the School of Dental Medicine, he and Claire Mitchell have worked together on a study of dental pain. Abdus-Saboor has also had productive conversations with researchers, such as Penn Dental Medicine’s Elliot Hersh, who are interested in applying his high-speed camera platform in clinical settings to objectively evaluate the patients’ pain and prescribe painkilling drugs appropriately.
“We’re not there yet, but these are conversations we’re starting to have,” says Abdus-Saboor. “If this technology could evolve into the clinic? That would be a wonderful thing.”
Ishmail Abdus-Saboor is the Mitchell J. Blutt and Margo Krody Blutt Presidential Assistant Professor in the Department of Biology at the University of Pennsylvania’s School of Arts and Sciences.