BY CHRISTINA SZALINSKI

EVERY MORNING, roughly 60 million American adults wake up in pain. Not the sharp, acute pain of a fresh injury that sends you for an ice pack, but the grinding, persistent pain that has lasted months or years—pain that has become a constant rather than a temporary warning.

The numbers are staggering. More people live with chronic pain than have heart disease, diabetes and cancer put together. It drains more money from the economy than all three combined and remains a leading cause of work-related disability. For those living with conditions like fibromyalgia, chronic back pain, irritable bowel syndrome or neuropathy, pain stops being a symptom and starts becoming a way of life. It dictates whether you can work, how you parent, whether you can make plans for the weekend.

Yet the medical system has struggled to provide answers. Unlike a broken bone visible on an X-ray or a disease detectable in blood work, chronic pain often has no clear source, no test to measure it and no straightforward path to relief. “There’s no blood test or scan that can prove exactly how much pain you have and how long you’ve had it,” says Hanna Grol-Prokopczyk, a medical sociologist and demographer in UB’s College of Arts and Sciences. Many patients end up bouncing from doctor to doctor, hearing variations of “we can’t find anything wrong” or “there’s nothing we can do.”

For decades, physicians turned to opioids as a primary solution, inadvertently fueling an addiction crisis that has claimed hundreds of thousands of lives. But even beyond addiction risks, opioids have proven ineffective for chronic pain. They quickly lead to tolerance, requiring higher doses for the same effect, and they work poorly for certain types of pain, particularly neuropathic pain—a type of chronic pain caused by damage or dysfunction in the nervous system.

The knowledge gap is as striking as the treatment gap. “As recently as 15 years ago, people weren’t really studying pain as a public health problem,” Grol-Prokopczyk observes. The medical establishment has gotten chronic pain wrong for decades—treating it like a symptom to fix rather than a complex condition involving the nervous system, mental health and social factors.

Today at UB, researchers are investigating chronic pain from every angle. Sociologists dig through data to figure out why some communities have a higher rate of pain than others. Behavioral medicine specialists develop psychological interventions that help rewire how the brain processes pain signals. Pharmacologists hunt for non-addictive alternatives to opioids, targeting novel receptors and ion channels. The researchers here share an understanding: Chronic pain isn’t one problem but many, requiring solutions as varied as the people who suffer from it.

Despite this massive impact, says Grol-Prokopczyk, “we’re just beginning to develop a solid evidence base for approaching chronic pain as a population health problem.” Her research examines pain through a sociological lens—tracking pain prevalence across geographic regions, sociodemographic groups and different countries, and examining patterns that might reveal underlying causes.

What she has found challenges conventional assumptions about pain. While physical factors like obesity rates correlate with increased pain—more weight means more stress on joints and backs—the story goes deeper. States with higher income inequality show greater pain prevalence. Countries with more gender or economic disparity report more pain. Even food insecurity appears linked to chronic pain, with states offering more generous SNAP benefits showing lower pain rates.

“There’s a real mix of physical and psychological factors that seem to underlie pain,” Grol-Prokopczyk explains. Her research suggests that psychosocial stressors may be as important as physical conditions in determining who develops chronic pain and why.

The COVID-19 pandemic offered an unexpected natural experiment. During lockdowns, chronic pain rates either plateaued or decreased—perhaps because people were less stressed staying at home or maybe because of the stimulus money many people received. But by 2023, pain shot up again, reaching an all-time high in the United States. This pattern hints at the complex interplay between lifestyle, stress and physical health in driving pain experiences.

One challenge Grol-Prokopczyk tackles in her research is measurement itself. Unlike blood pressure or cholesterol, pain has no gold standard measurement beyond self-report—there’s no way to prove exactly how much someone hurts. Different national surveys ask about pain in different ways, potentially measuring different phenomena. Her team is working to understand how these various measures compare and what they’re actually capturing when they claim to characterize pain across the population.

To understand why pain is so complex, Grol-Prokopczyk offers an analogy: Think of pain like a smoke alarm. It can go off when there’s an actual fire, but sometimes it triggers because your toast got too crispy or steam from a shower drifted too close. Either way, that alarm is ear-splittingly loud.

“Pain functions as the body’s alarm system,” she explains. “Sometimes it’s because something is pinching you, scratching you, burning you, some joint is wearing out ... But even when pain is a reaction to stress and your pain-sensing system becomes oversensitive and overstimulated, you’re genuinely feeling the pain, even if no one can point to a part of your body that seems injured.”

This understanding is crucial for a category of conditions—called chronic overlapping pain conditions—studied by Jeffrey Lackner, SUNY Distinguished Professor of Medicine in the Jacobs School of Medicine and Biomedical Sciences. COPCs include, among others, fibromyalgia, irritable bowel syndrome, migraines, temporomandibular disorders, chronic low back pain and chronic pelvic pain—disorders that can’t be explained by tissue damage or injury but seem to involve problems with how the central nervous system processes pain signals.

As principal investigator on the Irritable Bowel Syndrome Outcome Study, published in 2012, Lackner developed a cognitive behavioral therapy program designed to help patients gain control of their pain by targeting dysregulated brain-gut interactions.

A randomized, controlled trial completed in 2019 showed compelling results, with patients experiencing relief for up to 12 months post treatment. “That’s not the case with many medications,” Lackner notes.

Equally exciting is the fact that many of Lackner’s IBS patients not only experience less severe IBS symptoms after treatment, but less pain in co-occurring pain conditions. “If you target one chronic overlapping pain condition,” he explains, “you have this carryover therapeutic benefit that is seen in other chronic overlapping pain conditions.” Now Lackner is leading an NIH-funded clinical study examining the efficacy of his behavioral approach on chronic pelvic pain, “a significant problem for which there’s no satisfactory treatment and no physical pathology that adequately explains the severity of symptoms and their impact,” he says.

Temporomandibular disorders (TMDs), an umbrella term comprising some 30 debilitating conditions of the jaw and surrounding tissues, are another COPC that affects millions of people in the U.S. and resists simple medical solutions. A multidisciplinary team at UB involving researchers from the dental school, the medical school and the philosophy department is participating in a multi- institutional $17 million NIH study—part of the largest collaborative NIH study on TMDs to date—to better understand what they are and how to treat them.

Reflecting the complexity of TMDs, the grant is being disseminated to researchers across a plethora of disciplines, including bioinformatics, biomedical engineering, data science, epidemiology, joint mechanics, neuroscience, ontology and pain. “It brings together a critical mass of ideas and creates possibilities that never would have existed otherwise,”says Richard Ohrbach, professor of oral diagnostic sciences in the School of Dental Medicine and co-PI of the study.

Ultimately, the goal is similar to Lackner’s: to move beyond treating specific disorders and understand the bigger picture of chronic pain. Says co-PI Sonia Sharma, PhD ’18, MS ’11, assistant professor of medicine at the Jacobs School, “Our hope is to create a path that moves current treatment models out of the individual COPC silos to integrative holistic care.”

As promising as behavioral interventions are, many people suffering from chronic pain simply can’t manage without pharmaceutical intervention. Several pharmacological researchers at the Jacobs School are pursuing novel drug targets to meet that need. The urgency is clear: Opioids, while effective for acute pain, quickly lead to tolerance, physical dependence and potential addiction when used for chronic conditions.

“Opioids do not work well for chronic pain,” says Jun-Xu Li, professor of pharmacology and toxicology. His lab focuses on developing compounds that target different kinds of chronic pain, namely neuropathic and inflammatory pain. He’s had particular success targeting the imidazoline I2 receptor—a non-opioid target that appears effective in animal models for reducing both inflammatory and neuropathic pain without leading to tolerance or dependence.

In mouse models, the compounds show marked promise for neuropathic pain, which is notoriously hard to treat and responds poorly to opioids. Intriguingly, when combined with low-dose opioids, I2 receptor agonists achieve even better pain relief—potentially offering a way to harness opioid benefits while minimizing risks.

Arin Bhattacharjee and Amanda Klein, also in the department of pharmacology and toxicology, are studying ion channels, which are a bit like molecular doorways that control pain signals. Just as opening or closing a door controls who enters a room, these microscopic gates in nerve cells control the flow of electrically charged particles, determining whether pain messages reach the brain and how strong those messages are.

Klein focuses specifically on potassium channels, which she jokes are “the Rodney Dangerfield of the pain field, because they don’t get any respect.” These underappreciated channels play a crucial role in how opioids provide pain relief. But chronic opioid use appears to damage their function, which is part of the reason patients need increasingly higher doses over time and experience pain hypersensitivity when stopping the drugs.

“We think that these potassium channels normally work really well [to mitigate pain], unless you’ve been on opioids for a really long time,” she says. Her team is developing compounds to target these channels, potentially allowing people to wean off opioids while both improving their pain relief and avoiding symptoms of withdrawal.

Meanwhile, Bhattacharjee has achieved breakthrough results targeting sodium channels. His team developed a “molecular decoy”—a small protein fragment attached to a fat molecule that tricks the cell’s own machinery. Normally, a scaffolding protein protects the sodium channels that transmit pain signals, keeping them stable and functional. But Bhattacharjee’s decoy lures away this protective scaffold, leaving the pain channels vulnerable to destruction by the cell’s disposal system—effectively shutting off the pain signal.

“We’ve been able to show preclinically that if we give our decoy peptides locally, we can get three weeks of pain relief in animals,” Bhattacharjee says. Since the peptides act specifically on pain fibers, that means three weeks of relief from one injection, with no systemic side effects and no addiction risk.

The approach has been validated in human sensory neurons, and Bhattacharjee has cofounded two startup companies to advance different applications of the technology. Next, his team will complete toxicity studies to show that the peptides are safe before clinical trials can begin.

The breadth of UB’s chronic pain research—from population health studies to molecular mechanisms, from behavioral interventions to novel drug development—reflects the complexity of pain itself. There won’t be a magic pill that solves everybody’s chronic pain for all conditions. Instead, progress comes through understanding pain’s multiple dimensions and developing interventions for different aspects of the problem.

“In some ways, it boils down to: How do we make societies that are physically and mentally healthier?” Grol-Prokopczyk reflects. Her team continues identifying policies associated with lower pain rates, while developing better tools to measure and track pain across populations.

But policy changes take time, and people need help now. Earlier this year, the FDA approved Journavx (suzetrigine), its first non-opioid pain medication in decades—a sodium channel modulator that offers a new option for acute, short-term pain. Yet, as Bhattacharjee notes, it hasn’t proven effective for chronic pain.

As chronic pain reaches epidemic levels in America, UB researchers are attacking the problem from every direction—biological, psychological, social and political. They’re developing non-addictive drugs, testing ways to retrain patients’ brains and pushing for policy changes that could prevent pain before it starts. No single approach will solve chronic pain, but for the millions of Americans who wake up hurting every day, every bit of progress matters.