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Philanthropy’s Opportunity to Catalyze Pain Research

Chronic pain affects approximately 20% of Americans – private philanthropic support can help scientists not only understanding its origins, but develop more effective interventions to treat it in the future

It’s often called a silent epidemic. Yet the call for greater understanding of what causes chronic pain – with the hope of inspiring new and improved treatments – grows louder by the day.

It’s not a surprise. According to the 2019 National Health Interview Survey, more than 50 million American adults report experiencing pain most or all days of their lives. A large number of these individuals are unemployed or underemployed because of their pain. Persistent pain can lead to negative feelings and isolation, interference with the ability to foster strong relationships, and a significant uptick in suicidal thoughts. When you put the consequences of chronic pain together, the associated costs are staggering. Each year, chronic pain costs society hundreds of billions of dollars in healthcare expenses, disability payments, and lost productivity.

“All you have to do is look around you – someone you care about is likely affected by some type of chronic pain syndrome,” said David Julius, a physiologist at the University of California, San Francisco. Julius was awarded, with Ardem Patapoutian, the 2021 Nobel Prize in Medicine for their work on the molecular mechanisms of pain sensations. “It’s a quality-of-life issue for many people because it’s so disruptive. But it’s also a life and death issue. Chronic pain is something that clearly affects lifespan. Uncontrolled pain has physiological outcomes that make it harder to heal, harder to exercise, and just harder to take care of yourself. It’s become a unique driver of mortality – and one that needs to be addressed.”

Despite the prevalence of persistent pain, not only across the country but across the globe, there is no designated National Institute to drive research in chronic pain as you find with cancer, diabetes, or deafness. And while the National of Institutes of Health does provide funding for scientists studying different aspects of pain, the resulting dollar amounts are woefully inadequate.

“Upwards of 20% of the adult population in this country lives with chronic pain but less than 2-3% of the NIH budget goes toward its research. That’s a great mismatch, given the costs of this condition,” said Kathleen Foley, a neurologist emeritus at Memorial Sloan Kettering and a medical advisor or the Rita Allen Foundation. “Philanthropy can help to fill in that gap and shine a light on new areas in basic science that could help us make a real difference for these patients.”

Bishakha Mona, an associate advisor at the Science Philanthropy Alliance, wholeheartedly agrees. She says it is high time that funding agencies and private philanthropists understand that persistent pain is a disease, not just a symptom – and requires significantly more investment.

“The scientific community needs more funding so we can understand the core level of what’s changing in the nervous system that leads to chronic pain,” she said. “Philanthropies have a long history of funding promising researchers with interesting, and sometimes risky, ideas. In doing so, they often help to establish an new field of study. That’s what we need in chronic pain today.”

That’s why the Science Philanthropy Alliance has highlighted chronic pain as one of several underfunded research areas for philanthropists looking to make informed, effective, and satisfying investments in scientific research.

The State of the Field

Julius said there is great need for more basic science research in the pain field. It provides the “bedrock” for the novel therapies and interventions yet to be developed.

“There are still so many unknowns about what is happening in the brain and nervous system to translate acute pain into chronic pain,” he said. “We’re learning a lot about peripheral aspects of pain sensation – and one might argue that’s the simplest part of the problem. There’s still much left to be discovered, as we really don’t understand a lot about the molecular mechanisms that occur with injury or even what sort of biomarkers might give us a more objective assessment of pain. In terms of understanding pain in the context of what’s happening from a molecular standpoint in the central nervous system and spinal cord, it’s still the wild west.”

Carla Shatz, Neuroscientist at Stanford Neurobiology and Stanford Biology, and external scientific advisor for the Science Philanthropy Alliance, agreed – and added that there are exciting new opportunities to learn more about the fundamental changes in the brain that occur as acute pain transforms into persistent pain.

“There is uniform agreement that controlling pain from the outset is very important, but there is limited understanding of the mechanisms for how the brain’s inherent plasticity leads to long lasting changes in circuits and connections with chronic pain,” she said.

Diana Bautista, a pain researcher at the University of California, Berkeley, said basic science research has provided new clues into how the nervous system detects noxious thermal stimuli – yet how it detects noxious mechanical stimuli remains a mystery. She said it is imperative that we spend more time unveiling the “basic building blocks” of pain processing in order to find more effective options for treatment.

“It’s important to understand that pain is not just one thing,” she said. “There are many types of persistent pain disorders for which we don’t yet understand how the system goes awry. Understanding that at the peripheral level, the spinal cord level, and at the brain level is an area of vital importance for the future. By understanding the different molecular mechanisms by which you go from a normal pain state to a chronic pain state – and how that may happen in different disease contexts – is a challenge. And one that requires committed researchers and resources if we are to gain the insights we need to develop new targets for pain treatments.”

Foley, who is also a clinical researcher, said scientists like her rely on basic science findings to develop new treatments and interventions to help those living with chronic pain disorders.

“I think you only have to take a look at the work in migraine to see the power of basic science research to help patients,” she said. “Researchers in that area were able to understand the different receptors that play a role in triggering pain in headache. Without it, they would not have been able to develop the latest targeted therapies. My long-term view is that when we can look at chronic pain, and the diseases that lead to chronic pain, with a greater understanding of the molecular biology and genetics, we have an opportunity to be much more targeted in how we can block those pain signals. But that basic science work has to be done first.”

An Opportunity for Impact

So many big questions regarding pain are still unanswered. Elizabeth Christopherson, President and Chief Executive Officer of the Rita Allen Foundation, a philanthropic organization that supports early-career biomedical scholars, said there is a transformative opportunity for private philanthropists to have impact in pain research.

“People are astounded when they learn just how many people live with persistent pain,” she said. “Investing in discovery science and especially supporting early career investigators today can make an enormous long-term difference. Pain research scientists are ready to expand and accelerate their research inquiries to help chart the course for a deeper understanding of chronic pain, seeding hope for treatment and relief for millions of chronic pain patients.”

Bautista was named a Rita Allen Pain Scholar in 2010 and said the award provided a strong foundation to help her later establish her own laboratory.

“A lot of the approaches and questions we’ve pursued in my laboratory have been what many might call high-risk/high-payoff – we identified a big question that had not been answered in pain and then designed a series of experiments that may or may not work to discover new things,” Bautista said. “That type of research can have big payoffs, but it’s notoriously difficult to fund. Having private philanthropic funding sources has allowed me to take these kinds of risks – and it’s been incredibly fruitful in opening up new avenues of inquiry for us.”

Julius added that private philanthropy also plays a pivotal role in training the next generation of scientists – the scholars who will build off the work he and his colleagues have done to usher in new discoveries in the field of chronic pain.

“Every post-doctoral fellow who works in my lab has some kind of foundation fellowship,” he said. “It’s a great thing for their careers as it gives them a sense of independence and allows them to be more flexible in the kinds of things they want to study. It also brings people to pain research with new ideas, perspectives, and skill sets – giving our research new dimensions with new tools and approaches that can allow us to ask new and different questions.”

William R. Hearst III, and his wife Margaret, were inspired to provide funding for two Rita Allen Pain Scholars in 2021, with the hope that these enterprising young researchers will help provide new insights into chronic pain. Mrs. Hearst has lived with chronic pain for years – and the Hearsts are hopeful that today’s research findings can one day lead to tomorrow’s treatments.

Hearst said he understands that some private philanthropic organizations may be reticent to invest in basic science research because there’s no guarantee what researchers might find. But he believes it has the power to help scientists better understand pain’s underlying mechanisms and, ultimately, forge the paths to future therapies.

“It isn’t 100% clear what the application of these research studies should be – but that’s how science progresses,” he explained. “There should be some portion of philanthropy that goes to higher risk/higher reward projects. I like to think of it as the venture capital wing of philanthropy.”

Catalyzing the Field 

With more funding from private philanthropic organizations, scientist across the globe can expand and accelerate their research inquiries to help chart the course for a deeper understanding of chronic pain.

More investments in a pipeline of researchers are needed to address a growing global problem, where need and opportunity far exceed current investments. One barrier for funders is knowledge of the field and access to experts who can identify, review, and select scholars for support. To help overcome these barriers, the Rita Allen Foundation launched a program for pain research in 2009 and has provided opportunities for other philanthropic organizations and individual philanthropists, including Open Philanthropy and the Hearsts, to support scholars and learn more about this priority area of research.

“In collaboration with the U.S. Association for the Study of pain, we serve as a resource for other funders looking to consider supporting this research, where partnership is critical,” Christopherson said. “We are building a strong community of not only pain scholars, but scholars in other areas of biomedical research who are interested in pain. When other funders join in supporting early career investigators in this field of study, they will find that even modest investments can make an enormous long-term difference in catalyzing discovery—and resolving persistent pain.”

The Science Philanthropy Alliance also continues to work with like-minded organizations to educate philanthropists about the potential of basic science research. In partnership with the Rita Allen Foundation and Wellcome, they organized a virtual workshop in March of 2021, The Science of Pain, to discuss the latest advances in persistent pain research as well as opportunities for private philanthropists to help scientists better understand pain from the molecular to the behavioral level. The group also continues to advise philanthropists interested in scientific projects to invest in the science of pain.

For philanthropists, funding research to understand the experience of suffering at its most basic molecular and genetic level can empower promising young scientists to explore the vast unknowns of pain—seeding hope for treatment and relief.