Dec. 4, 2024 — Whether you’re visiting an orthopedic doctor for a broken bone, a dental surgeon for wisdom teeth removal, or your primary care physician about chest tightness, one of the most common reasons to seek medical care is pain.

“Pain is a component of every disease — Parkinson’s, Alzheimer’s, cancer, heart disease, anything,” said Rajesh Khanna, Ph.D., who studies the biology of pain at the University of Florida College of Medicine. “This is so critical because, while it’s something you can live with, it severely hampers your quality of life.”

Khanna, the Richard and Thelma O. C. Barney Term Professor in Pharmacology and Therapeutics, recently joined the university to become director of the new Pain Research and Integrated Neuroscience Center, or PRINC. Through PRINC, Khanna and a dozen researchers from across the Florida campus are combining their resources and expertise to investigate safe, healthy pain relief therapies, backed by funding from the National Institutes of Health’s Helping to End Addiction Long-term, or HEAL, Initiative.

While Khanna and other researchers focus on understanding the biological, mechanical, and psychological components involved in pain at the cellular level in animals, they aim to eventually work with colleagues to investigate viable treatments for people.

According to a 2023 National Institutes of Health study, more than 21% of Americans experience chronic pain, which can be continuous or intermittent and last at least three months.

Depending on the pain’s origin, current medications for treatment can range from nonsteroidal anti-inflammatory drugs, or NSAIDs, to muscle relaxers and opioids. With time, overuse of NSAIDs can lead to gastrointestinal issues and kidney problems. Opioids are highly addictive, and their overuse is a major part of the drug overdose crisis in the United States — contributing to more than 10,000 deaths annually, according to data from the National Institutes of Health’s National Institute on Drug Abuse.

Non-medical pain relief methods include physical therapy, meditation, and relaxation therapy. While these methods have reduced pain for many patients, they do not always provide the needed relief.

“Pain is a constellation of diseases at the whole-body level,” Khanna said. “It involves circuits in the brain and spine, cells throughout the body, neurons, proteins — lots of moving parts … This is not a case of one-size-fits-all, so we need input from a lot of different sources to get to the heart of it.”

One of Khanna’s frequent collaborators can often be found in the stables.

Ludovica Chiavaccini, D.M.V., a clinical associate professor at the UF College of Veterinary Medicine, has been a practicing equine veterinarian for more than two decades, specializing in anesthesia.

She became interested in studying ways to improve chronic pain in horses to avoid the undertreatment or overtreatment that happens because the animals, of course, can’t verbalize what they are feeling.

Chiavaccini partners with Khanna’s lab to investigate headshaking syndrome, a neuropathic condition that — like it sounds — causes a horse’s head to involuntarily shake violently. The syndrome has characteristics in common with some human neuropathic disorders.

“One of the limitations in human studies is that, when lab animals are being studied, they are not experiencing the exact same disease,” Chiavaccini said. “By studying horses with headshaking syndrome rather than trying to replicate similar conditions in something like a mouse model, we’re looking at a more realistic clinical model that might lead to successful treatments for people.”

Chiavaccini’s analysis on animal pain has also inspired her to use innovative technologies that can help veterinarians better care for future patients. Using artificial intelligence, her team has studied the facial expressions of farm animals to detect when they are experiencing pain without being handled, which can worsen their injuries in some cases. She hopes to gather more data on characteristics like sounds and body movements that also can indicate pain.

“It will take time before getting to this point, but I can envision us using this method to take a video and use an app to have supplemental data,” Chiavaccini said.

The goal, she said, is not to replace veterinary examinations, but rather to provide more data that complements expert knowledge in order to bolster diagnosis and treatment options.

To better understand how to treat pain, researchers like Robert Caudle, Ph.D., are hoping to better understand its origins.

Caudle, a professor in the UF College of Dentistry, has studied the differences between acute — or short-term — pain and chronic pain, and the different ways circuits in the body react to them.

He and his colleagues are involved in the National Institutes of Health RE-JOIN Consortium, a collaboration of several institutions studying joint pain from different angles. At Florida, Caudle and colleagues are looking into the specific neurons involved with jaw and knee pain in older animals.

“It’s known that, as you get older, you’re more susceptible to chronic pain, and particularly arthritic pains,” Caudle said.

Nearby at the UF Herbert Wertheim College of Engineering, biomedical engineer Blanka Sharma, Ph.D., is studying ways to preserve or regenerate joints that can alleviate pain for degenerative diseases like osteoarthritis.

Sharma and her team develop biomaterials that work by filling deteriorated cartilage tissue, restoring mobility, and reducing pain — similar to the way a pothole can be paved over to repair a road and make it safe for drivers again.

Studying the impact of osteoarthritis therapies can be difficult, she said, because it takes time for researchers to study the long-term impact of any treatments in animal models. Arthritis is usually a condition that takes time to develop, which is why it is also common among older adults.

“We hope some of the therapies we develop can actually make their way into the clinic,” Sharma said.

Khanna’s lab at the College of Medicine is working on multiple projects to target key proteins involved in pain pathways, with a goal of tweaking the proteins that will “turn down the volume” on pain safely.

His team has identified channels that can serve as “volume knobs” for pain. By targeting or mutating the proteins using gene therapy techniques, pain flare-ups can be halted in animals.

However, researchers are trying to improve this technique because it is actually a bad thing for humans not to experience any pain, as it can signal danger. For example, when someone touches a hot stove, pain prompts them to quickly withdraw their hand, preventing tissue damage. Khanna’s team is making headway on perfecting changes to these protein pain volume knobs, thanks to excellent resources at Florida, which is widely considered a top-ranked institution for gene therapy research.

His lab is also collaborating with a group in Italy to bioengineer proteins in a way that can control the sensation of pain through a novel technique.

The teams are exploring “adaptronics,” smart biomaterials that do not exist in nature, to produce a nontoxic material that people can put on their skin over painful sites. The targeted neurons will calm inflammation without completely turning off the body’s pain receptors.

Khanna is excited about the possibility of patients finding chronic pain relief that may only require one or two doses of an injection or topical medication over the course of a year, rather than a daily pill.

“The adaptronic is a protein that’s been manufactured by your body, and it would only activate when there is inflammation and you need pain relief, so there is no risk of addiction,” Khanna said. “This is the work we’re doing that’s really leading-edge, and we hope to take it much further.”

Caudle added that new tools and technologies will allow pain researchers, and eventually people who are experiencing chronic pain, to reap the benefits.

“Right now, there is probably more funding and interest in pain research than there ever was before in my career,” Caudle said. “Historically, pain has been looked at as a symptom rather than a disease. With the HEAL Initiative, more institutions are investing in it and realizing this is something that needs to be addressed.”