Where Pain Research Is Headed and Why I’m Hopeful

By Dr. Lynn Webster

If you live with pain, you’ve probably heard promises that “something better is coming.” At this month’s Pain Therapeutics Summit in San Diego, you could see that promise taking shape. For two days, clinicians, scientists, companies and advocates compared notes on what’s working, what’s not, and what’s next.

Threaded through much of it was the National Institutes of Health’s Helping to End Addiction Long-Term (HEAL) Initiative -- an NIH-wide push launched in 2018 to accelerate better pain care and reduce opioid-related harms.

HEAL exists because of the opioid crisis; Congress gave NIH an initial $500 million in fiscal year 2018 to jump-start a coordinated research plan, and the NIH has since invested several billion dollars to keep the effort moving. In other words, HEAL is a rare silver lining: a tragedy spurring a sustained, practical response.

(The HEAL Initiative was not directly hit by any funding cuts in 2025. However, the Trump administration has proposed cutting the NIH budget by 40% next year, which could potentially impact HEAL funding.)

Since its launch, HEAL has grown into a national engine for discovery. NIH reports a cumulative investment approaching $4 billion, supporting more than 2,000 projects across all 50 states, and helping advance 40-plus new drugs and devices to FDA investigational status.

This is a sign that the pipeline is broader and closer to patients than it has been in years. Think of HEAL as scaffolding: trial networks, shared data standards, and coordinated teams that help good ideas climb faster from lab to bedside.

A decade ago, analgesic research often looked like isolated bets. Today, it feels more like a coordinated campaign. That doesn’t guarantee success, but it raises the odds that something useful will reach doctors and patients.

Just as important, what’s coming isn’t a single “miracle drug” but a wider toolkit. You’ll see more non-opioid medicines designed around the biology of different pain types; safer use of existing tools that can lower the need for higher doses when opioids are used; devices and neuromodulation approaches that calm overactive nerves or brain circuits; smarter drug delivery systems that make treatments last longer or act locally at lower doses; and digital health that captures how people actually live -- including their sleep, activity, and pain flares -- so that care decisions track real life, not just clinic visits.

The studies themselves are changing, too. Many people don’t have just one pain condition; they have overlapping problems. Newer trials are beginning to mirror that reality and to focus on outcomes you can actually experience -- walking farther, sleeping better, and participating more in life -- rather than only chasing a number on a pain scale.

Researchers are also building better signposts, such as biomarkers and other objective measures, to predict who will benefit from which therapy and who may be at risk of long-term pain after injury or surgery.

Signposts aren’t a substitute for what people tell us about their pain. In research and development, objective measures help compare treatments and identify who is most likely to benefit. Once a therapy reaches the clinic, those measures become guides, not verdicts, and should be read alongside the patient’s narrative so that care reflects how the person actually lives and feels.

HEAL has made these shifts a priority by funding large, practical datasets and endpoints that regulators and payers can use.

Here’s the clear-eyed part: many of the drugs and devices discussed at meetings like this will not make it past the investigational stage. That’s how science works. But when trials are well designed and data are shared, today’s misses can more quickly lead to tomorrow’s wins -- and the lessons won’t vanish into a file drawer.

Some analgesic candidates will cross the finish line, and even modest gains -- better sleep, fewer flares, less brain fog, or an extra hour of activity -- can change a life. Across millions of people, small wins add up to something transformative.

What does this mean if you’re living with pain right now? Expect more choices and more personalization. Conversations with your clinician may start to include options that didn’t exist a few years ago, and you may hear about clinical studies built around everyday life rather than rigid clinic schedules. If a trial is a good fit, participating in one will help move the field forward.

Most of all, there’s a reason for hope that is grounded in real progress, not hype.

None of this happened by accident. The NIH HEAL Initiative has been the engine behind much of it -- steady funding, coordination, and a focus on solutions that reach the bedside. Keeping that engine running is how promising ideas become practical relief.

Lynn R. Webster, MD, is a pain and addiction medicine specialist and serves as Executive Vice President of Scientific Affairs at Dr. Vince Clinical Research, where he consults with pharmaceutical companies.

Dr. Webster is the author of the forthcoming book, “Deconstructing Toxic Narratives -- Data, Disparities, and a New Path Forward in the Opioid Crisis,” to be published by Springer Nature. Dr. Webster is not a member of any political or religious organization.

Researchers Replicate Human Pain in Lab Dish

By Crystal Lindell

Researchers have replicated part of the human nervous system in a lab dish, a method they hope will allow them to study pain and potential treatments without having to inflict pain on humans. 

The research was shared in a study published in Nature, and led by Sergiu Pasca, MD, a Professor of Psychiatry and Behavioral Sciences at Stanford University.

Pasca and his colleagues used stem cells to recreate the four key neurons involved in the “pain pathway” that processes pain in humans. Specifically, they made sensory neurons, spinal cord neurons, thalamic neurons, and cortical neurons, and put them all together. Then they added capsaicin, which is present in hot chili peppers, to see how the neurons respond to painful stimuli. 

They found that the lab dish neurons will sense the pain through specialized receptors and emit electrical signals throughout the pain pathway, just as they do in humans. 

“That makes us believe that we have actually reconstructed the basic component of this pain circuit,” Pasca explains. 

In a video about the findings, Pasca describes how they did the research and why it matters. 

The findings could allow researchers to study pain in humans in a way that doesn’t cause actual pain to humans or research animals. Human pain has often proven tough to study in laboratory animals.

“Their pain pathways are in some respects different from ours,” Pasca said. “Yet these animals experience pain. Our dish-based construct doesn’t.”

The hope is that being able to reconstruct or to build this pain pathway in the lab will allow researchers to study human genetic disorders and other conditions that cause pain, and then eventually to start testing drugs for alleviating pain. 

“This neural circuit in a dish offers us an exciting way to study disease and to speed up drug discovery and therapeutic applications -- essentially providing us with a working model of a very important part of our human nervous system,” Pasca said. 

It’s All In Your Head: How Brain Circuitry Causes Placebo Effect

By Crystal Lindell

The placebo effect is very real. But how and why it happens has mostly remained a mystery. 

However, new research may shed light on what exactly is happening in our brains when just the expectation of pain relief is sufficient for people to feel better, even when the pill or treatment they’re taking has no therapeutic value.

The discovery may even lead to new treatment options. 

In studies on laboratory mice, researchers at the University of North Carolina School of Medicine discovered a pain control pathway that links the front of the brain, through the middle region of the brainstem, to the cerebellum in the back of the brain.

They then showed that certain parts of this pathway are activided in mice when they anticipate pain relief. 

“Our results do open the possibility of activating this pathway through other therapeutic means, such as drugs or neurostimulation methods to treat pain,” says lead researcher Greg Scherrer, PharmD, associate professor in the UNC Department of Cell Biology and Physiology, who conducted the study along with colleagues at Stanford, the Howard Hughes Medical Institute, and the Allen Institute for Brain Science. 

The research, recently published in the journal Nature, provides a new framework for investigating the brain pathways underlying other mind-body interactions beyond the ones involved in pain.

“We all know we need better ways to treat chronic pain, particularly treatments without harmful side effects and addictive properties,” Scherrer said. “We think our findings open the door to targeting this novel neural pain pathway to treat people in a different but potentially more effective way.”

How Scientists Studied Placebo Effect

The placebo effect is basically the brain’s way of trying to help us feel better. As such, just the expectation of pain relief is often enough to make our brains release hormones and natural chemicals that provide relief. Positive thinking and even prayer have been shown to provide similar benefits to patients, without the use of medication. 

The scientific community’s understanding of the placebo effect primarily came from human brain imaging studies, which showed increased activity in certain brain regions. However, those studies did not have enough precision to show what was actually happening in those brain regions. 

So Scherrer’s team designed a set of complex experiments to learn in more detail what was happening in the brain.

First, they created a method to generate in mice the expectation of pain relief. Then they used a series of experiments to study the anterior cingulate cortex (ACC) of their brains, which had previously been associated with the placebo effect. 

The experiments helped them see the intricate neurobiology of the placebo effect on the receptors, neurons, and synapses of the brain. When mice expected pain relief, it boosted signaling along the pain pathway.

“There is an extraordinary abundance of opioid receptors here, supporting a role in pain modulation,” Scherrer said. “When we inhibited activity in this pathway, we realized we were disrupting placebo analgesia and decreasing pain thresholds. And then, in the absence of placebo conditioning, when we activated this pathway, we caused pain relief.”

In a 2021 study, researchers had a similar breakthrough when studying the placebo effect. Researchers at Dartmouth University conducted an analysis of neuroimaging studies involving over 600 healthy people who participated in placebo studies. Their findings showed that placebo treatments reduced pain-related activity in multiple areas of the human brain.

Researchers Closer to Finding the Gene for Hypermobile EDS

By Crystal Lindell

We may be one step closer to discovering the specific gene mutations behind hypermobile Ehlers-Danlos syndrome (hEDS) — a connective tissue disorder that weakens collagen, muscles, ligaments and organs throughout the body, and makes joints highly flexible.

A research team at the Medical University of South Carolina has released the results of a genetic study of a family with high rates of hEDS. Five out of 11 family members met the clinical diagnostic criteria for hEDS and three were considered “probable.” 

Before we get too far into its conclusions though, it’s important to note that findings were released as a preprint in Research Square, which means they have not yet been peer-reviewed by a journal. As such, it’s in the early stages of release, and further scrutiny may result in changes to the conclusions.

That said, the researchers claim to have found what could be a variant linked to hEDS in the Kallikrein-15 gene, which is primarily expressed in the thyroid gland and other organs.

To check if this gene change actually causes hEDS, researchers used laboratory mice. After modifying the mice to have the same genetic variant, they found that the mice had similar connective tissue problems as seen in people with hEDS.

This supports the idea that the Kallikrein gene changes may play a role in causing hEDS.

But the research does not seem to show an all-encompassing hEDS gene. In a cohort of 197 hEDS patients, they found that less than a third (32.8%) had at least one KLK variant. Which means that over 60% of hEDS patients in the study did not have the variant.

As of now, hEDS is the only type of Ehlers-Danlos syndrome that does not have a known specific genetic marker, so finding one would be monumental. And even if this research doesn’t get us all the way there, it’s a huge step in the right direction.

Previous research has also associated hEDS to a genetic variant that causes a deficiency of folate, the natural form of Vitamin B9.

I should note here that I was diagnosed with hypermobile-EDS in 2018, so I have a lot of interest in the topic on a personal level. Since there is no genetic test currently available for hEDS, I was diagnosed via a physical assessment, along with my family’s medical history.

A lot of hEDS patients worry that if there ever is some sort of confirmed, definitive test like a genetic marker, they may not have the marker and would then “lose” their diagnosis.

Based on my personal experiences with medical professionals, I think that’s a legitimate fear. Doctors already seem unwilling to diagnose clear cases of hEDS for a variety of reasons, and this could just give them another excuse to continue doing that.

All I can really say is that if it happened to me, I would feel confident in knowing that my body is clearly not “normal” — so even if it’s not hEDS, there is something else impacting my health.

Some patients diagnosed with hEDS may actually be suffering from something else -- so a genetic test might help them to get the right diagnosis and treatment. I know that probably sounds naively optimistic to many patients. The more likely result is doctors telling patients nothing is wrong with them, and then sending them on their way to suffer.  

On the other hand, I think hEDS is so under-diagnosed, that having a definitive test for it would result in many, many more people finally getting an hEDS diagnosis.

Discovering the exact gene responsible for hEDS could also result in better treatments going forward. As of now, most doctors tell hEDS patients that there’s no cure, so all they can really do is treat the symptoms as they arise and avoid activities that could make their condition worse.  

This is purely wishful thinking, but perhaps in the future researchers will someday discover a way to actually strengthen our collagen and connective tissue, which could have countless benefits for patients suffering from the pain and other common hEDS symptoms.

Advancements like that still feel a long way off though, so until they happen, helping people get an hEDS diagnosis through a genetic test would be progress for millions of patients.

New Society Launched to Advance Pain Research

By Gregory Carbonetti, Guest Columnist

“I live with layers of chronic pain,” writes Dr. Richard Hovey, a professor of dentistry at McGill University. Diagnosed with psoriatic arthritis and enduring lower back pain from a bicycling accident, Hovey also faces painful chemotherapy for advanced metastasized prostate cancer.

“The combination of these pain-inducing events presented significant life-changing challenges to retaining my sense of personhood,” Hovey wrote in a personal essay in the Journal of Patient Experience.

Many Americans may relate. Chronic pain is more prevalent in the U.S. than diabetes, coronary heart disease, stroke and cancer combined. It costs our economy some $635 billion a year in direct treatments and lost productivity.

These problems are exacerbated by the ongoing opioid epidemic, which claimed approximately 450,000 lives over the last two decades and stigmatized people who take prescription pain medication. The nation, and the world, lacks efficient and safe pharmaceutical treatments for pain.  

Thus, one might think a scientific and professional society comprising scientists, clinicians, healthcare providers and policymakers exists, working to reduce the burden of pain. There was such a group, the American Pain Society, but it filed for bankruptcy in 2019. This absence was rectified only this past December with the inaugural meeting of the United States Association for the Study of Pain (USASP).

The circumstances leading to the formation of this new organization underlie the importance of pain research in the United States, which scientific societies play a fundamental role in. They foster interdisciplinary collaboration among members; attract young investigators through early-career grants; work to increase policy impact and address social issues; and promote members’ personal and research integrity.

Scientific societies bring together diverse perspectives and translate knowledge into directives for action. The death of the old pain society and the birth of a new one illustrates the importance of transparency for societies of every discipline.

The now-defunct American Pain Society did some good work. It provided clinical guidelines for pain treatments, increased funding for research, and advocated for multidisciplinary care. But it became a victim of toxic philanthropy, tarnished by its connection to opioid manufacturers such as Purdue Pharma, which settled criminal and civil charges last year by agreeing to pay $8.3 billion for its role in the opioid crisis.

Purdue and other opioid manufacturers accounted for nearly $1 million of the American Pain Society’s $6.5 million in contributions between 2012 and 2017, according to a U.S. Senate committee report, and covered over 5% of the society’s expenses during those years.  

The American Pain Society wasn’t the only professional society accepting donations from opioid manufacturers. The Academy of Integrative Pain Management, which accepted approximately $1.3 million between 2012 and 2017, also dissolved in 2019 due to financial problems. While its focus was different, both societies shared members, and its loss was another setback.

For many pain researchers, clinicians and advocates, the American Pain Society’s demise meant losing important support for their work. These professionals soon had difficulty meeting with pain management leaders and experts in other sub-specialties and disciplines.

More Transparency Needed

Many members were stunned by what had transpired, unaware of the American Pain Society’s dependence on opioid manufacturers. According to the Pacific Standard, when the society’s contributions from opioid manufacturers began to dwindle, leaders never directly told members that fewer industry donations were contributing to their financial problems. 

The dissolution of the American Pain Society created a vacuum, and strategies to organize the USASP began. Forming the new society included a GoFundMe campaign to purchase the old society’s Journal of Pain through auction.

While membership in the USASP is similar to the American Pain Society, its leaders stress that they have learned valuable lessons, making the new constitution and expectations of leadership more transparent and talking with members about the role industry will hold. The USASP is committed to “values-based” decision-making.  

Creating a new society will not instantly end either the chronic pain crisis or the opioid crisis. Nor will it absolve certain players of their past errors. Nonetheless, this history should push other scientific societies to strive toward full transparency and remain in service to those they seek to help.

Dr. Hovey wrote of the transformation “that occurs as patients become people again and are awakened by the multitude of challenges that [lie] ahead of them.”

The formation of the United States Association for the Study of Pain is a significant moment for chronic pain research and for sufferers like Dr. Hovey. The work of rebuilding vital infrastructure for understanding and managing chronic pain, the invisible epidemic, begins anew.

Gregory Carbonetti, PhD, is a Civic Science Fellow at the Alan Alda Center for Communicating Science, working to more meaningfully connect science and research with diverse communities and our shared civic life.

This column is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.