Beyond Opioids: The Promise of Pain Research

Rena D'Souza and Rebecca Baker
NIH leaders Rena D’Souza and Rebecca Baker headlined the inaugural NYU Pain Research Center Symposium.

By Rick Valachovic, DMD, MPH, Clinical Professor and Director of the NYU Dentistry Center for Oral Health Policy and Management

Dentists are all too familiar with the realities of pain. It motivates many patients to walk through our doors, and it results from many of the procedures we do. In short, pain mitigation is essential to our practice.

Most of us were taught to treat dental pain with opioids. These drugs are highly effective, but as we’ve learned, they are also addictive and even deadly. According to the National Institute on Drug Abuse, opioid overdoses killed more than 106,000 people in the United States in 2021 alone.

How did we get here? While dentists are not responsible for the opioid epidemic, we contributed to the problem. Dental pain requires strong medicine, and in the late 1990s, dentists were among the top specialty prescribers of opioids. Especially troubling, research suggests that opioid use and abuse among teenagers may be linked to having their “wisdom teeth” removed. Many teens received their first opioid prescription from the dentist who extracted their third molars.

Dentists prescribe a lot fewer opioids today, thanks in large part to a group of Boston dental educators who developed strategies for preventing and managing prescription drug misuse in dental settings. The Commission on Dental Accreditation has also helped reduce opioid use by revising its standards to emphasize dental students’ competencies in local anesthesia, pain, and anxiety control. (You can learn more about these initiatives and other steps dentists have taken to curb the opioid epidemic in a 2020 issue of Dental Clinics of North America, to which I contributed.)

What hasn’t occurred is the discovery of a treatment for pain that can rival opioid’s effectiveness. “As dentists we should be spearheading the research to understand this problem, especially when it relates to dental pain or any pain in the head and neck,” says my colleague Brian Schmidt, DDS, MD, PhD, senior vice dean for research development and academic affairs at NYU Dentistry. “It’s on us to try to figure out better solutions.”

Seizing the Moment

Brian’s interest in pain is not purely scientific. An oral and maxillofacial surgeon specializing in oral cancer, Brian sees pain up close on a regular basis. Because oral cancers are located in the mouth and throat, they trigger pain in the course of chewing, speaking, and even swallowing – unavoidable activities that occur throughout the day. As a result, oral cancer patients report more pain and more severe pain than other cancer patients.

Brian is now part of an interdisciplinary effort to tackle pain at NYU Dentistry: the NYU Pain Research Center. The brainchild of Nigel Bunnett, BSc, PhD, who chairs our department of molecular pathobiology, the Center was launched in 2022 to spur the development of novel therapies that can replace opioids.

Both Brian and Dean Charles Bertolami saw the proposed Center’s potential to build on the College’s unparalleled expertise in oral cancer pain at a time when federal concern about the opioid crisis has elevated pain research at the National Institutes of Health (NIH). By adding world-class researchers investigating pharmacology, bioengineering, the gut-brain connection, and the neurobiology of pain to the NYU Dentistry faculty, the Center is poised to play a leading role in this national effort.

From the Lab to the Clinic

“Drug discovery is a long, expensive, and complex path, so we can’t count our chickens before they hatch,” says Rajesh Khanna, PhD, MSc, the Center’s director and a professor of molecular pathobiology, “but if something comes out of these investigations to find non-opioid solutions to pain, that could be useful on a global scale.” Rajesh and his colleagues at the Center are exploring how pain signals travel through the body and how those signals might be disrupted by a diverse array of therapies. These include the use of biologics (drugs derived from living organisms), green LED light, and allosteric modulators (drugs that bind with their targets in a way that produces fewer side effects). The Center’s researchers are also working to build on the knowledge of pain signaling derived from rodent models by mapping those pathways in humans.

These efforts are not only fascinating; they also hold promise for improving the lives of millions of people with chronic pain, but only if they are translated into clinical applications. That’s where the Center’s associate director for clinical and translational research, Kara Margolis, MD, comes in. Kara is pursuing yet another avenue of research: the gut-brain connection. As a pediatric gastroenterologist, she studies disorders that affects both the brain and the gastrointestinal (G.I.) tract in children.

“I am looking at which comes first, gastrointestinal problems and pain, or anxiety, depression, and related behavior disorders. If we can figure that out, we may know how to target treatment better,” she says.

Promising Investments

Although an estimated 50 million U.S. adults live with chronic pain, the NIH has never had an institute devoted to its study, but the NIH has created opportunities for pain research. Investigators inside and outside NYU learned about these efforts on March 7, when the Center held a day-long symposium featuring Rena D’Souza, DDS, MS, PhD, director of the National Institute of Dental and Craniofacial Research and Rebecca G. Baker, PhD, director of the NIH HEAL Initiative, a trans-agency effort to speed scientific solutions to stem the opioid crisis.

NIH funding will be critical to supporting the Center’s research. Its investigators currently have $44 million in federal funding, $19 million of which is focused on oral cancer pain research occurring in collaboration with the NYU Dentistry Translational Research Center and the NYU Oral Cancer Center, both of which Brian directs. These investments, coupled with NYU Dentistry’s investment in top research talent and the Center’s focus on interdisciplinary collaboration, hold tremendous promise. On the educational side, the Center should prove influential in how pain mitigation is taught throughout NYU’s health professions’ programs. On the clinical side, it should advance changes in practice.

The Center’s creation has also raised Brian’s hopes that after his 20 years of oral pain research, substantial progress may be in sight. “I now have access to experts who have no idea about oral cancer, but they’re trying to understand all cancer pain. That’s a step that I never thought would happen in my career. If one of their discoveries from our basic science laboratories advances to a clinical trial, that would be a huge success,” Brian says.

We’ve made some progress since the 19th century, when physicians treated Ulysses S. Grant’s oral cancer with regular doses of cocaine, but most of the task of finding non-addictive treatments for oral and other types of pain lies before us. Exposing scientists to patients with pain and clinicians to pain research is one way in which the Center can accelerate this progress. That work is urgently needed to bring promising therapies into routine care.

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