Pain may be a universal experience, but what actually causes that experience within our brains is still poorly understood. Pain often continues long after the relevant receptors in the body have stopped being stimulated and can persist even after those receptors cease to exist, as is the case with “phantom limb” pain.
The exact experience an individual will have after a painful incident comes down to the complex, variable connections formed between several different parts of the brain. The inability to predict how those connections will form and evolve can make pain management a tricky, frustrating endeavor for both healthcare providers and patients.
Now, a team of Penn researchers has shown a way to make such predictions from the pattern of neural connections that begin to take shape soon after the first onset of pain. Though their study was conducted in rats, it suggests that similar brain imaging techniques could be used to guide treatment decisions in humans, such as which individuals are most likely to benefit from different drugs or therapies.
The study, published in the journal Pain, was led by Beth Winkelstein, Eduardo D. Glandt President’s Distinguished Professor in Penn Engineering’s Department of Bioengineering and Deputy Provost of the University of Pennsylvania, along with Megan Sperry, then a graduate student in her lab. Eric Granquist, Director of the Center for Temporomandibular Joint Disease at the Hospital of the University of Pennsylvania in the Department of Oral & Maxillofacial Surgery, and assistant professor of Oral & Maxillofacial Surgery in Penn’s School of Dental Medicine, also contributed to the research.
“Our findings provide the first evidence that brain networks differ between acute and persistent pain states, even before those different groups of rats actually show different pain symptoms,” says Winkelstein.
We hope you will join us for the Fall 2019 Herman P. Schwan Distinguished Lecture by Dr. Gordana Vunjak-Novakovic, hosted by the Department of Bioengineering.
Date: Wednesday, November 6th, 2019
Time: 3:30-4:30 PM
Location: Glandt Forum, Singh Center, 3205 Walnut Street
Speaker:Gordana Vunjak-Novakovic, PhD, University Professor, The Mikati Foundation Professor of Biomedical Engineering and Medical Sciences, Columbia University in the City of New York
The classical paradigm of tissue engineering involves the integrated use of human stem cells, biomaterial scaffolds (providing a structural and logistic template for tissue formation) and bioreactors (providing environmental control, dynamic sequences of molecular and physical signaling, and insights into the structure and function of the forming tissues). This “biomimetic” approach results in an increasingly successful representation of the environmental milieu of tissue development, regeneration and disease. Living human tissues are now being engineered from various types of human stem cells, and tailored to the patient and the condition being treated. A reverse paradigm is now emerging with the development of the “organs on a chip” platforms for modeling of integrated human physiology, using micro-tissues that are derived from human iPS cells and functionally connected by vascular perfusion. In all cases, the critical questions relate to our ability to recapitulate the cell niches, using bioengineering tools. To illustrate the state of the art in the field and reflect on the current challenges and opportunities, this talk will discuss: (i) anatomically correct bone regeneration, (ii) bioengineering of the lung, (iii) heart repair by a cell-free therapy, and (iv) the use of “organs on a chip” for patient-specific studies of human physiology, injury, healing and disease.
Funding: NIH, NSF, New York State, Mikati Foundation, Schwartz Foundation
Gordana Vunjak-Novakovic is a University Professor, the highest academic rank at Columbia University that is reserved for only 16 professors out of 4,000, and the first engineer in the history of Columbia to receive this highest distinction. She is also the Mikati Foundation Professor of Biomedical Engineering and Medical Sciences, and on faculty in the Irving Comprehensive Cancer Center, College of Dental Medicine, Center for Human Development, and Mortimer B Zuckerman Mind Brain Behavior Institute. She directs the Laboratory for Stem Cells and Tissue Engineering that is a bioengineering lead of the Columbia Stem Cell Initiative and a home of the NIH Tissue Engineering Resource Center. She also serves on the Columbia President’s Task Force for Precision Medicine and the Executive Leadership of the Columbia University Medical Center. She received her Ph.D. in Chemical Engineering from the University of Belgrade in Serbia where she was on faculty until 1993, holds a doctorate honoris causa from the University of Novi Sad, and was a Fulbright Fellow at MIT.
The focus of her research is on engineering functional human tissues for regenerative medicine and studies of development and disease. Gordana published 3 books, 60 book chapters, 400 articles (including those in Nature, Cell, Nature Biotechnology, Nature Biomedical Engineering, Nature Communications, Nature Protocols, PNAS, Cell Stem Cell, Science Advances, Science Translational Medicine). With over 44,000 citations and impact factor h=121, she is one of the most highly cited individuals. She gave 420 invited talks, and has 101 licensed, issued or pending patents. With her students, she co-founded four biotech companies: epiBone (epibone.com), Tara Biosystems (tarabiosystems.com), Xylyx Bio (xylyxbio.com), and Immplacate (immplacatehealth.com).
She is a member of the Academia Europaea, Serbian Academy of Arts and Sciences, National Academy of Engineering, National Academy Medicine, National Academy of Inventors, and the American Academy of Arts and Sciences.
Megan Sperry, a Ph.D. student in the Department of Bioengineering, is a recipient of a Student Design and Research Award from the Biomedical Engineering Society (BMES). Megan works in the Spine Pain Research Lab of Beth Winkelstein, Ph.D., professor of Bioengineering and Vice Provost for Education at Penn’s School of Engineering and Applied Science, as well as with Eric Granquist, DMD, MD, an oral and maxillofacial surgeon at Penn Dental Medicine.
With Drs. Winkelstein and Granquist, Megan studies temporomandibular joint (TMJ) pain and osteoarthritis, the latter of which can develop as a long-term consequence of untreated TMJ dysfunction. There’s currently no way to determine which patients will progress to TMJ osteoarthritis, so Megan’s extended abstract, which was submitted to the BMES competition, detailed a study using 18F-EF5 PET, an imaging modality used mainly in oncology. Hypothesizing that hypoxia, or low oxygen, was a key factor in the development of TMJ osteoarthritis, Megan studied the relationship between hypoxia and persistent TMJ pain and found that hypoxia preceded reorganization of the cartilage of the TMJ, part of the process culminating in TMJ osteoarthritis (see image below).
“This project has been both fun and challenging because it brings together concepts and techniques from multiple fields, including orthopedics, neuroscience, and, with the use of 18F-EF5, radiation oncology,” Megan said. “I’m excited to have the opportunity to share my work at the BMES Annual Meeting and receive feedback as we continue to move the project forward.”
Each year, BMES awards up to five graduate students the Student Design and Research Award from dozens of submissions. Congratulations to Megan for this elite recognition of her research!