by Michael D. O’Neill
BioQuick News recently had the opportunity to speak with Stephen Waxman, MD, PhD, on the occasion of his receiving the prestigious Sharpey-Schafer Award from the UK-based Physiological Society for his ground-breaking discoveries beginning in the 1980s on “peripheral sodium channels,” that led to the development of the first-in-class non-addictive non-opioid drug (Jounavx) for acute pain relief. The drug works by blocking a pain-transmitting sodium voltage-dependent channel (Nav1.8) in peripheral nerves, so that the pain signal does not reach the brain. It is the first new acute pain treatment in more than 20 years and the first that specifically targets a pain-signaling protein (Nav1.8) found only in the peripheral nervous system, thus avoiding side effects in the central nervous system. Journavx was developed and is marketed by Vertex Pharmaceuticals and was approved by the FDA on January 30, 2025. The Sharpey-Schafer Award recognizes advances in translational studies that move progress from the lab to the bedside of patients in the clinic.
Bestowed every three years by the Physiological Society, the prize honors distinguished contributions to physiology that significantly advance scientific knowledge and public health. Past recipients include Nobel Laureates Torsten Wiesel (1981, visual cortex) and Erwin Neher (1991, single ion channels).
Dr. Waxman’s efforts to develop pain medications and to study ways to regenerate nerve sensation have been supported by decades of financial funding from Paralyzed Veterans of America (PVA) and he expressed profound gratitude for PVA’s long support, which began in 1988 with PVA’s financial assistance in establishing the Yale Center for Neuroscience and Regeneration Research. Dr Waxman is the founder and long-time director of this center. Commenting on the collaboration with PVA, he said “this partnership has been essential in propelling our research team’s progress over many years. The PVA-Yale collaboration serves as an excellent model of a highly productive partnership.”
In addition to Dr. Waxman, BioQuick spoke with PVA National President and Chairman of the Board Robert Thomas on the significance of the pain drug advance that resulted in the award.
“For nearly 80 years, PVA has championed vital research that improves the quality of life for Veterans with spinal cord injuries and diseases (SCI/D), like MS and ALS,” said Thomas. “This achievement is a powerful reminder that investing in research can deliver life-changing results, giving disabled Veterans and all people living with acute pain the chance to lead fuller, more active lives. PVA applauds Dr. Waxman for this important work and is honored to have helped fund the foundational research that made this innovation possible.”
The Sharpey-Schafer Award is the second major award Dr. Waxman has received from the Physiological Society. In 2009, he was honored with the Society’s Annual Prize (the Society’s premier award), an accolade he shares with his “heroes” 1963 Nobel laureates Andrew Huxley, Sir John Eccles, and Alan Hodgkin, who discovered sodium channels and made advances in understanding synapses, all without the use of the sophisticated instrumentation that is available today. Such was the prescient insight of Hodgkin and Huxley that their equations for nerve impulses are still used today. The Nobel was given “for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane.”
Dr. Waxman (born in 1945) is an American neurologist and neuroscientist. He served as Chairman of the Department of Neurology at Yale School of Medicine and Neurologist-in-Chief at Yale-New Haven Hospital from 1986 until 2009. As of 2023, he is the Bridget Flaherty Professor of Neurology, Neuroscience, and Pharmacology at Yale University. He founded the Yale University Neuroscience & Regeneration Research Center in 1988 and is its director. He previously held faculty positions at Harvard Medical School, MIT, and Stanford Medical School. He is the editor-in-chief of The Neuroscientist.
Two types of sodium channels – “molecular batteries” – are present in pain-signaling nerve cells but not in the brain. Waxman’s landmark research showed that both are essential for pain signaling, and established each of them as a target for new medications that could mute pain without the potential for addiction.
In his discussion with BioQuick, Dr. Waxman first recounted the story of “man on fire” disease (inherited erythromelalgia, IEM). In this disease, there is severe burning pain due to overactivity in the small fiber sensory nerves and skin redness periodically from birth. Waxman reasoned that, because this disease is inherited, the genes of patients with IEM could point to the molecules involved in pain-signaling. In 2004, Waxman discovered that mutations in the SCN9A gene, which provides instructions for making Nav1.7 mutant channels, from families with IEM, make dorsal root ganglion (DRG, peripheral and sensory) neurons hyper excitable, thereby demonstrating the mechanistic link between these mutations and pain, and firmly establishing over-activity of Nav1.7 channels as the molecular basis for a severe pain syndrome. These channels, which transport positively charged sodium atoms (sodium ions) into cells, act as a trigger for generation and transmission of electrical signals that produce pain.
In December 2006, a University of Cambridge team reported an SCN9A mutation that resulted in a complete lack of pain sensation in a Pakistani street performer and some of his family members. He felt no pain, walked on hot coals and stabbed himself to entertain crowds. By 2013, nearly a dozen gain-of-function mutations of Nav1.7 had been linked to IEM. The multi-decades search which identified mutated gene SCN9A as the cause of inherited erythromelalgia is documented in a 2018 book by Dr. Waxman, Chasing Men on Fire: The Story of the Search for a Pain Gene.
But Waxman also showed that Nav1.7 does not work alone. Like a domino, it works together with another sodium channel, Nav1.8. Waxman’s lab played a pivotal role here also. Along with his studies on Nav1.7, Waxman discovered the important role of Nav1.8, which acts like a partner with Nav1.7 in pain signaling. As early as the 1980s, Waxman’s work had indicated that a “slow” sodium channel (a channel that remains open for an unusually long time) was essential for pain signaling. In ensuing years, this slow sodium channel was found to be Nav1.8. Waxman’s team showed that, while Nav1.7 acts like a trigger, Nav1.8 channels produce almost all of the electrical current needed for pain signaling. “Nav1.7 and Nav1.8 work together. I think of Nav1.7 as the fuse, and Nav1.8 as a firecracker”, noted Waxman.
Dr. Waxman also hypothesized that there might be “pain resilience” genes, which dispose individuals to pain resistance. In a study of individuals who had high pain thresholds, his group sequenced all 23,000 genes in each of these subjects and did identify a gene whose mutation was associated with pain resistance. That gene codes for potassium voltage-dependent 7 (Kv7) channel protein.
In the second story, Dr. Waxman mentioned work on the study of nerve function within the brain and spinal cord in multiple sclerosis (MS). Some patients with MS experience paralysis from which they can actually recover. This is called a remission. In his studies of remissions in MS, Dr. Waxman examined this and found that sodium channels were normally situated in the periodic narrowed regions of the myelin sheath surrounding the axons. The myelin sheath is reduced or destroyed in MS and the newly demyelinated regions at first do not have sodium channels. Dr. Waxman found though that some patients could generate new sodium channels in the naked myelin regions. These new sodium channels act to boost impulse transmission, and these patients regained sensation and movement. Work continues on advancing these compelling findings beyond MS.
Dr. Waxman mentioned that he was considered for the 2008 Physiological Society Annual Award, but did not win it then. Instead, the award went to Sir Robert Edwards for his work on in vitro fertilization (IVF) that has now helped hundreds of thousands of parents have children. Dr. Edwards’ IVF work was recognized with a Nobel Prize in 2010. Dr. Waxman noted the many thousands of families helped by IVF[SW1] . The Physiological Society Award clearly honors major achievements that have the potential of helping society.
Dr. Waxman drew an analogy between the recent work with ion channels with the early work on statins. He noted that the first results with statins were relatively weak but provided proof of principle, and that the second- and third-generation statins became blockbuster drugs. He thinks that hopefully there might be a similar advance in the expanding world of ion channel-focused drugs. It should be noted that the statin advance was propelled by the genetic underpinnings of the inherited disease hypercholesterolemia. Similarly, the genetic underpinnings of ion channel diseases like IEM is providing guidance to further pain drug development.
In closing, Dr. Waxman had a message for young people, encouraging them to pursue careers in science, noting that he had found his career in biomedical research to be the “best job in the world.” It involves solving puzzles and that is fun, he said and also lays the rewarding foundation of possibly helping society with the solutions.
Robert Thomas, President of Paralyzed Veterans of America (PVA)
Robert Thomas is the current National President of Paralyzed Veterans of America (PVA). PVA is the only nonprofit Veteran Service Organization dedicated solely to helping veterans with spinal cord injuries and diseases (SCI/D), to include multiple sclerosis (MS) and Lou Gehrig’s disease (ALS or amyotrophic lateral sclerosis). The organization has 16,000-17,000 members and will celebrate its 80th anniversary next year.
Thomas was effusive in his praise of Dr. Waxman and his success in identifying the first-in-class non-addictive non-opioid acute pain reliever Journavx, the first new class of acute pain relievers (blockers of Nav1.8 sodium channels in peripheral nerves) developed in over 20 years. While Nav1.8 and other peripheral sodium channel blockers have not yet been shown to prevent chronic pain, Dr. Waxman’s studies continue to investigate this longed-for possibility.
Thomas grew up in Cleveland, Ohio where he played high-school football and basketball. Shortly after graduating high school in 1987, he enlisted in the U.S. Army. Thomas served as a power generation equipment specialist at Fort Sill, Oklahoma; Camp Humphreys, South Korea; and Fort Bragg, North Carolina.
In 1991, at the age of just 21, while on active duty in North Carolina, Thomas severed his fifth and sixth vertebrae in a diving accident incurred while on a swimming excursion. His legs were paralyzed and his arms and hands were weakened. He was introduced to PVA through the Cleveland VA Medical Center. PVA helped him navigate his new life by working to obtain his earned benefits through the VA and reintegrating him back into society through social outings with the recreational therapist.
Thomas joined PVA in 1992 as a member of the Buckeye Chapter in Ohio, and a little while later, began volunteering with the chapter. He took some time off to earn his associate degree in Information Technology and returned to the Buckeye Chapter of PVA board in 2010. He served as the chapter’s vice president from 2012-2015, and as the chapter’s representative on the national Field Advisory Committee and the Resolution Committee.
Thomas was re-elected for his third term as National President of PVA in May 2025 during the organization’s 79th Annual Convention, to begin a new, one-year term on July 1, 2025. He initially joined PVA leadership at the national level in 2015 as the parliamentarian, and was elected to serve on the Executive Committee in 2017. Thomas continues to serve PVA because he wants to help lead the organization well into the future.
“My inspiration to serve stems from PVA’s past and present leadership,” Thomas says. “Being a member for over 30 years (he’s 56 now) and seeing how unselfishly each leader, member, employee, and volunteer gives of themselves makes me want to continue to serve an organization that does so much for veterans and the disabled community.”
In addition to serving as President, Thomas currently serves as the Chair ofPVA’s Research Foundation. This group decides how the PVA allocates funding for research seeking the next big breakthrough to help those with spinal cord injury and disease live better. Since its inception in 1976, the Research Foundation has invested 644 grants for a total of over $54 million. In last year alone, the Foundation funded nearly $800,000 in grants. The grants fund in the following categories:
- Basic Science – Laboratory research in the basic sciences to find a cure for SCI/D.
- Clinical – Clinical and functional studies of the medical, psychosocial, and economic effects of SCI/D, and interventions to alleviate these effects,
- Design and Development – Of new or improved rehabilitative and assistive technology/devices for people with SCI/D to improve function, which also includes improving the identification, selection. and utilization of these devices.
- Fellowships – For postdoctoral scientists, clinicians and engineers to encourage training and specialization in the field of spinal cord research.
Over decades, the Foundation has funded Dr. Waxman’s revolutionary studies at over $9 million and also helped finance the building of the Yale Center for Neuroscience and Regeneration Research in 1988.
Thomas has also recently been appointed to the VA’s Family Caregiver and Survivors Advisory Committee.
Thomas and his wife, LaShon, whom he first met in middle school, live in Macedonia, Ohio. Thomas enjoys reading, watching sports, and playing adaptive sports like power soccer, bowling, air guns, and scuba diving.
“PVA has changed my life by introducing me to things that I believed to be over when I became injured, such as the National Veterans Wheelchair Games, and showing me that you can still live a fulfilling life although you have sustained a catastrophic injury.”
BioQuick News applauds the productive collaboration between Dr. Waxman’s group and PVA and hopes that new research will open a path to relief of chronic pain and perhaps even to the regeneration of lost movement in SCI/D.
