University of Rochester | Ernest J. Del Monte Institute for Neuroscience Vol. 26 - 2025
Decoding Chronic Pain
Insights from Psychiatry, Dentistry, & Anesthesiology
John J. Foxe, PhD
Kilian J. and Caroline F. Schmitt Chair in Neuroscience
Director, Ernest J. Del Monte Institute for Neuroscience
Professor & Chair, Department of Neuroscience
Director, Golisano Intellectual and Development Disabilities Institute
FROM THE DIRECTOR’S DESK
Thereis an uneasiness; you are not alone if you are feeling it among the scientific community. Our country’s scientific engine, which has long been a pillar of American progress and leadership, is shifting. The longstanding foundation set into motion by our forefathers does not feel as sturdy.
Established by our first president in 1790, the Intellectual Property Law was added to the Constitution to foster scientific and artistic advancements. Following World War II, the federal government’s support of science ballooned. It established a model to fund scientific advancement, especially for projects related to public health and national security, evolving into the transformation of the National Institutes of Health, the world’s premier biomedical research funding agency.
a global pandemic. Because of science, our mothers, sisters, wives, daughters, and friends are evading a breast cancer diagnosis. Because of science, we are saving babies who come into this world weeks before they should be outside of their mother’s womb. Because of science, HIV is a treatable condition instead of a death sentence.
ON THE COVER:
From left: Paul Geha, MD, Eli Eliav, DMD, PhD, MBA, and Jennifer Gewandter, PhD, MPH, stand with the 9.4T MRI. This powerful resource is providing researchers at the University of Rochester fine detail imaging.
Photo: John Schlia Photography
More than a century of certainty has turned into uncertainty almost overnight. Like you, I am trying my best each day to stay the course and continue to ask the questions that we as scientists know will get us closer to the answers we all want as human beings: how do we keep ourselves and loved ones healthy, protected, and cured of disease?
We are in a new era, a new chapter of science. I’m sure this moment will be a headline in a textbook someday. But how that headline reads is now up to us. More than ever, science is needed.
Because of science, we just overcame
Del Monte Institute for Neuroscience Executive Committee
John Foxe, PhD
Chair, Department of Neuroscience
Bradford Berk, MD, PhD
Professor of Medicine, Cardiology
Robert Dirksen, PhD
Chair, Department of Pharmacology & Physiology
Diane Dalecki, PhD
Chair, Department of Biomedical Engineering
Jennifer Harvey, MD
Chair, Department of Imaging Sciences
Robert Holloway, MD, MPH
Chair, Department of Neurology
Paige Lawrence, PhD
Chair, Department of Environmental Medicine
Hochang (Ben) Lee, MD
Chair, Department of Psychiatry
But there is still so much we do not know, so much left to learn and discover. We know this as scientists, which is why we must continue to move our field forward. How we do this is through persistence. We may have to shift our way of thinking, get creative in ways we have not been pushed to, and look for funding outside of the engine that has kept us running for so long. Collaborations will be vital now more than ever, sharing ideas, resources, and data. I’m grateful that team science is already baked into the work environment of the University of Rochester.
This is how we make that future headline ours, how science comes out stronger than before. But it will take the majority, and I know it will not be easy. We are alongside you, and we will be ever better as scientists and a world for it.
In Science,
John J. Foxe, PhD
Shawn Newlands, MD, PhD, MBA
Chair, Department of Otolaryngology
Webster Pilcher, MD, PhD
Chair, Department of Neurosurgery
Steven Silverstein, PhD
Professor, Department of Psychiatry
Duje Tadin, PhD
Chair, Department of Brain & Cognitive Sciences
Editor/Writer
Kelsie Smith Hayduk
Kelsie_Smith-Hayduk@ urmc.rochester.edu
Contributors
Mark Michaud, Karen Black
Feature Photography
John Schlia Photography
Volume 26 | Fall 2025
2 NEWS BRIEFS
How 'forever chemicals' impact the developing brain, slowing Huntington's disease, the brain's immune cells role in vision health, and more discoveries.
4 REVEALING
PAIN IN THE BRAIN
Chronic pain affects more people than heart disease, cancer, and diabetes combined. How a diverse group of researchers are turning to the brain for answers.
8 Q & A: ELISE PIAZZA, PHD
The Assistant Professor of Brain and Cognitive Sciences and Neuroscience aims to understand how the brain organizes natural sounds & how multiple people’s brains and behaviors align to support interpersonal communication.
9 POSTDOC SPOTLIGHT: LUCA FRANCHINI, PHD
The postdoctoral fellow in the Orlandi Lab investigates ligands and signaling mechanisms of orphan G-protein coupled receptors expressed in the brain.
CAN THE BRAIN HELP PREDICT CHRONIC PAIN RISK LISTEN TO OUR PODCAST
Researchers Discover how Genetics
Shape
Social Organization and Group Behavior
Groups of social animals, including humans, can make complex decisions without a central leader. However, those choices aren’t always made by the bulk of the group. Sometimes, a small number can influence the majority to adopt its preferences—a phenomenon called “minority influence.”
Takao Sasaki, PhD, an associate professor in the Department of Brain and Cognitive Sciences, published a study in the Proceedings of the National Academy of Sciences (PNAS) that found a surprising genetic underpinning in fire ants to the “minority influence” phenomenon. The research offers insights into how social interactions shape individuals and groups.
Fire ants are highly social insects. Researchers found that in the fire ant colonies, a small group of worker ants can carry a selfish genetic element, a piece of DNA that exists to spread itself, even if it doesn’t benefit its host. These ants can influence a single-queen colony to accept additional queens that also carry this selfish genetic element. As a result, a colony that would normally have just one queen can shift to accepting multiple queens. These findings deepen our understanding of how genetic factors shape social organization and collective behaviors, providing insight into the evolution of cooperation and sociality.
Glial Replacement Therapy Slows Huntington’s Disease in Adult Mice
Huntington’s disease has long defied attempts to rescue suffering neurons. A study led by Steve Goldman, MD, PhD, co-director of the University of Rochester Center for Translational Neuromedicine, published in Cell Reports, shows that transplanting healthy human glial progenitor cells into the brains of adult animal models of the disease not only slowed motor and cognitive decline, but also extended lifespan. The researchers believe that transplanting healthy support cells could become part of a multi-pronged treatment strategy, either alone or alongside a gene-targeting approach. Future research will need to determine the optimal delivery, dosing, and timing for this strategy. Beyond that, combining glial replacement with other therapies, such as lowering mutant huntingtin expression and replacing lost neurons, may yield even greater benefits. Huntington’s disease is a hereditary brain disorder caused by a mutation in the huntingtin gene.
Researchers Find “Forever Chemicals” Impact the Developing Male Brain
“Forever chemicals” or per- and polyfluoroalkyl substances (PFAS) have been widely used in consumer and industrial products for the better part of a century, but they do not break down in the natural environment. One PFAS, perfluorohexanoic acid or PFHxA, is made up of a shorter chain of molecules and is thought to have less of an impact on human health. New research from Ania Majewska, PhD, professor of Neuroscience and senior author of the study published in the European Journal of Neuroscience suggests otherwise, finding that early life exposure to PFHxA may increase anxiety-related behaviors and memory deficits in male mice. The effects, while mild, are reminiscent of the many neurodevelopmental disorders that are male-biased and suggest that the male brain may be more vulnerable to environmental insults during neurodevelopment. Research has shown, males are more often diagnosed with neurodevelopmental disorders such as autism and ADHD.
Researchers Aim to See if Neurons Can Transport Light Like Fiber-Optic Communications
Channels
Scientists have found hints that, along with firing electrical pulses to communicate throughout the central nervous system, neurons may transmit light as well. This could profoundly change current models of how the nervous system works. A grant from the John Templeton Foundation is supporting this research by Pablo Postigo, PhD, professor at Rochester’s Institute of Optics, and Michael Telias, PhD, assistant professor of Ophthalmology and Neuroscience. Postigo, an expert in nanophotonics, will design probes that are able to interact optically with living neurons, and Telias will measure the electrical properties of neurons and their action potentials. If researchers discover that light is at play and can understand why, it could have major implications for medically treating brain diseases and drastically change the way physicians heal the brain.
Researchers Find Brain Immune Cells Regulate Vision Health
by J. Adam
During most eye infections or injuries, neutrophils, immune cells found in the blood, are usually the first line of defense. However, Jesse Schallek, PhD, associate professor of Ophthalmology and senior author of a study published in eLife, discovered that the retina responds differently than many other tissues in the body. When photoreceptor cells in the retina are damaged, microglia, or the brain’s immune cells, respond, and the neutrophils are not recruited to help despite passing through nearby blood vessels. Using adaptive optics imaging, a camera technology developed by the University of Rochester that allows the imaging of single neurons and immune cells inside the living eye, researchers studied the retinas of mice with photoreceptor damage. They found that while both neutrophil and microglia cells are present in the retina, only microglia cells respond to photoreceptor injury, and they do not call upon neutrophils to help repair the photoreceptor damage. Researchers believe this suggests a type of cloaking occurs during retinal injury to protect the retina from a rush of immune cells that could do more harm than good.
Photo
Fenster / University of Rochester
THE WEB OF CHRONIC PAIN
How Transdisciplinary Pain Research Looks to the Brain for Answers
One in five. That is how many adults suffer from chronic pain in the United States. It affects more people than heart disease, diabetes, and cancer combined. That is more than 50 million people who may not be able to work or participate in everyday activities. But despite its enormous human toll, it is a condition that is still measured subjectively. The gold standard is to rate one's pain on a scale from 0 to 10 on how minor to extreme or intense the pain is in the moment and often in the past 24 hours.
“I would not be that ambitious to say that we are going to measure pain objectively, but would say that what we are trying to do is come up with quantitative measures that are richer than the standard scale, and that are valid in the sense that every time you measure them you tend to get the same answer and it will tell you a lot about what the patients are going through,” said Paul Geha, MD, associate professor of Psychiatry, Neuroscience, Dentistry, and Neurology. Geha’s research has identified structural changes in the brain of people who suffer from chronic pain, but his work has also shown that there may also be a way to predict who is at risk of developing chronic pain. “There are changes in the white matter of the brain. These are people out there who don’t have chronic pain now, but their brain is more susceptible to developing a chronic pain condition.”
For Geha, pain and the brain exist in tandem. “All pain is psychological because we really need to be conscious to feel pain,” Geha said. “We feel pain with our brains, not with our knees and our backs, and in that sense, all pain is psychological. And all pain has a psychological component that is what we need to start with and understand that the injury model does not go far enough to explain the patient's problems.”
Discovering How to Measure Pain and Risk
Eli Eliav, DMD, PhD, MBA, serves as Director of the Eastman Institute for Oral Health at the University of Rochester. He provides care for patients with chronic orofacial pain and leads a research program dedicated to uncovering the mechanisms and risk factors that contribute to the development of chronic pain. His work addresses a range of conditions, including chronic pain that follows dental procedures, nerve injuries, and other chronic orofacial pain disorders. In his laboratory, Eliav and his team have developed several animal models to study neuropathic pain, including models for orofacial pain and spinal nerve injury. Their findings show that animals with strong endogenous pain modulation systems, the central nervous system’s ability to reduce or
“We feel pain with our brains, not with our knees and our backs, and in that sense, all pain is psychological.
Paul Geha, MD, Eli Eliav, DMD, PhD, MBA, and Jennifer Gewandter, PhD, MPH, review images from the 9.4T MRI in the Center for Advanced Brain Imaging & Neurophysiology at the Medical Center.
augment pain, are less likely to develop chronic pain after nerve injury. In contrast, those with impaired modulation often experience more severe and widespread pain following injury.
The research team includes Qian Wang, PhD, who leads the basic science efforts, along with collaborators from other institutions. To evaluate pain modulation, they use conditioned pain modulation in humans, where one painful stimulus reduces the perception of another, and exercise-induced hypoalgesia—a decrease in pain sensitivity after exercise—in both humans and animal models. These approaches have revealed fundamental differences between individuals with effective and less effective pain modulation, including distinct gene expression patterns. These discoveries may lead to new therapeutic targets that strengthen the body’s pain regulation systems and reduce the likelihood of chronic pain following injury.
The team has also identified differences in how animals with varying pain modulation capacities respond to medications commonly used for pain management. These findings support the potential for more personalized approaches to pain prevention and treatment. Eliav says the ability to identify patients at higher risk before surgery or injury could help tailor treatment strategies and guide the development of new therapeutic options.
This is some of the research he is now collaborating with Geha on. While Eliav translates his animal models to humans, Geha looks to do the opposite: reverse translation to investigate what he has already found in humans. In previous
research, Geha discovered that in humans, changes in the volume of the nucleus accumbens, a component of the limbic system of the brain, can indicate if someone is at a greater risk of developing chronic pain. Using rat models from the Eliav lab, and the 9.4 Tesla magnet, a high precision MRI machine that allows detailed imaging of small structures, they have found similar brain changes, as Geha has found in humans. This reverse translation allows researchers to ask more specific questions about the brain and look at mechanisms, genes, proteins, and cells—anything that may be involved in causing, predicting, or preventing chronic pain. “To conduct pain research, a multidisciplinary approach is key,” Eliav said. “There will never be one molecule or one drug that will solve all the pain problems in the world.”
Treating the Whole Patient – Biopsychosocial Model – No One Answer or Solution
The history of pain research can be traced to the field of Anesthesiology. Robert Dworkin, PhD, professor of Anesthesiology and Perioperative Medicine, Neurology, and the Center for Health + Technology, began working in the field in 1982. “We have appreciably more evidence-based pharmacologic treatments, and the use of interventional approaches such as neuromodulation has also increased greatly,” Dworkin said. He has participated in and led dozens of clinical trials for chronic pain treatments over the last three decades. Along with the internal resources available to translational researchers to design and conduct clinical trials on chronic pain, Dworkin points out that a clinical approach developed in the 1970s at the Medical Center is an essential factor in pain research and care. “The one very important consistency over all these years is that state-of-theart treatment for chronic pain is multidisciplinary, typically including physicians, nurse practitioners, physician’s assistants, psychologists, physical therapists, and others. This treatment approach reflects the fact that chronic pain is almost always a truly biopsychosocial condition.”
He is also the director of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), a public-private partnership with the US Food and Drug Administration that helps set the international agenda for pain research. And since 2001, he has co-chaired the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). “Both initiatives remain very active and have ongoing efforts involving, for example, multi-lab replicability of an animal model of neuropathic pain, recommendations for conducting clinical trials of central sensitization, and identification of substance use disorder phenotypes in a large multicenter study,” said Dworkin.
From left: Janet Pennella-Vaughan, MS, NP, Senior Nurse Practitioner, Pain Services, Director, Clinical Research; Tammy Ortiz, Senior Grants Management Specialist; Research Administrator, and Robert Dworkin, PhD
HISTORY OF BIOPSYCHOSOCIAL MODEL
George Engel, MD, internist and psychiatrist, spent most of his career at the University of Rochester Medical Center and conceptualized the biopsychosocial model in the late 1970s. He suggested that to understand a person’s medical condition, biological, along with psychological and social factors, also had to be considered. The biopsychosocial model continues to be used and taught to future doctors at the Medical Center and the School of Medicine and Dentistry.
Team Science Leads to Discovery
Jennifer Gewandter, PhD, MPH, is an associate professor of Anesthesiology and Perioperative Medicine, Dentistry, Neurology, and Neurosurgery. Her research focuses on designing and implementing high-quality randomized clinical trials (RCTs) for chronic pain. She and her team conduct NIH- and industry-sponsored RCTs of non-pharmacologic and pharmacologic interventions for chronic pain. Her newest project is focused on developing a mind-body connection program using yoga to treat chronic pain. Along with physical poses to increase strength and mobility, this holistic pain care aims to help patients manage the impact of their pain on their daily life through breath work and meditation. “Yoga has been shown to improve sleep disturbance, fatigue, and anxiety, which are symptoms that commonly occur with chronic pain. There is literature to support these benefits, but the big gap in the literature is how to get people who are living with chronic pain and likely have decreased mobility to try it and keep it up,” Gewandter said. “My goal is to develop a program that will help
people start the physical poses at a level that is appropriate for their current physical capabilities. I hope to avoid having people stop after a few classes because it is too challenging, allowing them to stick with it long enough to feel the amazing benefits that a full yoga practice can provide for both the body and the mind.”
Gewandter is also working with Geha on a few chronic pain studies including investigating whether language or facial expressions can be used to characterize different types of chronic pain and predict whether spinal cord stimulation is likely to work in chronic lower-back pain patients receiving this treatment. This research aims to develop an algorithm, based on keywords, phrasing, and/ or facial expressions, to predict pain severity.
Working with Neurosurgeon Steven Solder, MD, in the Neuromedicine Pain Center, Geha and Gewandter are recruiting people living with pain who are undergoing spinal cord stimulation. Prior to permanent implantation of a spinal cord stimulator, patients must go through psychological clearance, but that is only designed to make sure important diagnoses, like PTSD or substance abuse, are not missed. This research could someday replace that step and also add the ability to predict the possible outcome of the procedure, which nationally averages about a 50 percent success rate.
“Potentially, this tool can be used to predict how well someone will respond to something like a spinal cord simulator,” Gewandter said. “We know that people who are very depressed or have high pain catastrophizing, for example, they can't imagine their pain getting better, are less likely to respond to a spinal cord stimulator or any surgery for that matter.”
“There is an improved understanding, I think, across disciplines, about the psychological aspect of pain. It’s not just related to muscles, tendons, and bone, but it is also related to the nerve fibers, the spinal cord, the brain stem, the cortex, all are processing and receiving input,” Geha said. “When someone comes in with back pain, they do not think to refer them first to a psychologist to talk about life experience or how they started to get pain – first they get an injection, and I think this needs to change to move the field forward.”
BASELINE DAY 5 DAY 14
Image from 9.4T MRI/PET, courtesy Arefin Laboratory.
Q&A with Elise Piazza, PhD
Elise Piazza, PhD, is an assistant professor of Brain and Cognitive Sciences and Neuroscience at the University of Rochester. She completed her undergraduate degree in Cognitive Science and Music at Williams College, her PhD at the University of California, Berkeley, and her postdoctoral training as a C.V. Starr Fellow at the Princeton Neuroscience Institute. Today, her research aims to understand how the brain organizes natural sounds, including speech and music, and how multiple people’s brains and behaviors align to support interpersonal communication.
Summarize your research
My research focuses on the cognitive and neural mechanisms of human auditory perception and communication. More specifically, a few active projects investigate how neural and behavioral alignment between people support successful real-life dialogue, how listeners track the statistics of others’ voices to infer identity, emotional tone, and social traits, and how expertise shapes the hierarchical processing of music, i.e., features like notes, chords, and phrases. I use a combination of behavioral and computational approaches as well as fMRI, EEG, and functional near-infrared spectroscopy (fNIRS), a non-invasive neuroimaging technique that uses near-infrared light to measure changes in blood oxygenation in the brain, which are associated with neural activity.
How did you become interested in your field?
In high school, I was debating whether to pursue clarinet performance at a conservatory or a more well-rounded liberal arts education. I chose Williams College, where I majored in both Cognitive Science and Music. I had opportunities to conduct research in several labs and perform with some really innovative ensembles. I soon became aware of the field of music cognition, including one pivotal moment that involved hearing Diana Deutsch discuss her auditory illusions on a podcast, and I conducted a senior thesis on the influence of expertise on musical memory. Over the years, my interests
have migrated to multisensory integration, speech, and communication, but I have maintained a thread of music cognition research throughout, and it is a major component of my lab today.
What brought you to the University of Rochester?
I was drawn to UR for several reasons. First, its interdisciplinary Brain and Cognitive Sciences program aligned with my background better than most traditional Psychology departments. Second, the University has an incredibly rich auditory/music research community, which has only strengthened since I’ve been here, with multiple faculty hires, a world-class music cognition symposium, and the new SoundSpace Institute. Last but not least, I actually grew up in Rochester and have a large extended family here.
What is your favorite piece of advice?
I have a few pieces of advice. First, push yourself to pursue ideas and events outside of your own core area of research. I have found success in interdisciplinary research because of its immense creative potential, and I love working on teams of people with diverse perspectives and expertise. Attending talks and conferences a bit outside of my core area has stimulated some of my best ideas and collaborations. Also, lab culture has a direct impact on research. The labs in which I’ve been most productive have had very healthy, positive cultures, so I’ve tried to build a supportive community in my own lab by hiring people who are kind and generous as well as brilliant, which has been invaluable.
Luca Franchini, PhD
Luca Franchini, PhD, is a postdoctoral fellow in the Orlandi Lab at the University of Rochester Medical Center. Franchini received his degree in Pharmacy from the University of Bologna in Italy, and completed his PhD in Pharmacological, Experimental and Clinical Sciences at the University of Milan, where he studied molecular mechanisms of synaptic plasticity associated with NMDA receptors in the hippocampus.
“I have always been interested in science since I was a kid. I remember one day my parents gifted me a microscope and I really enjoyed taking a closer look at what surrounds us,” Franchini said. “During my pharmacy studies, I really enjoyed chemistry and pharmacology, and I decided to take advantage of my thesis project to move abroad and challenge myself with a lab experience in a different culture and language.” He developed the thesis for his Pharmacy degree at the Karolinska Institute in Sweden. It explored the role of oxysterols in cognitive resilience to aging.
Today, Franchini works in the lab of Cesare Orlandi, PhD, assistant professor of Pharmacology and Physiology, where he investigates ligands and signaling mechanisms of orphan G-protein coupled receptors expressed in the brain.
Recently, he spearheaded research that aims to advance large-scale drug screenings. Working with Orlandi, Associate Professor John Lueck, PhD, and fellow postdoctoral fellow Joe Porter, PhD, the team developed GzESTY, a new
SUMMER OF NEUROSCIENCE
method to better understand the largest group of cell surface receptors, GPCRs, which currently account for a third of existing drug targets. Many of these receptors are not fully understood, especially those with unknown natural activators. This research, published in Nature Communications, used the GzESTY tool to detect the presence of activators for two orphan receptors in the mouse brain. Researchers used a Keyence microscope to verify receptor expression and their plasma membrane localization in this research. A Del Monte Institute for Neuroscience pilot grant helped the Orlandi Lab acquire this tool in 2021.
“The opportunity to be a part of the Orlandi Lab at the University of Rochester is why I moved to the United States,” said Franchini. “It matched my pharmacology background, and we shared the same interest in providing novel pharmacological targets and pathways for future therapeutic strategies.”
The Del Monte Institute for Neuroscience Commission spent the summer training undergraduate scholars through the NEUROCITY program, giving hands-on experience to high school students through NEURORocHS, and NEURO2ALL members stopped by a Rochester summer camp to teach kids about the brain.
