Scripps Research scientist are understanding pain from a cellular level to develop new therapies.
Neuroscientists have long questioned how the brain interprets complex sensations like touch or pain. Scripps Research is determined to provide answers. Spearheaded by a team of experts led by professor and Nobel laureate Ardem Patapoutian, the institute is transforming our understanding of how we experience physical sensations—and how those insights can lead to better treatments for chronic pain.
This interdisciplinary effort is made possible in part by Scripps Research’s unique culture of collaboration, which has enabled breakthroughs in ways that other institutions cannot match.
“Scripps Research has allowed me to build a team of scientists that’s not only diverse in expertise but also incredibly collaborative,” says Patapoutian, who’s also a Howard Hughes Medical Institute Investigator and the Presidential Endowed Chair in Neurobiology. “That’s what sets us apart.”
The Marvel of Touch
One remarkable aspect of human physiology is our sense of touch. It’s so finely tuned that we can detect indentations as small as one five-hundredth the diameter of a human hair, a sensitivity at the nanometer scale. Beyond helping to navigate the physical world, our sense of touch plays a profound role in emotional health and is related to the sense of proprioception, which is the sense of where our body parts are in space.
“Proprioception is one of your most important senses,” Patapoutian says. “It’s what allows us to walk, dance and even play musical instruments without having to look at our hands.”
As part of understanding proprioception, Patapoutian’s lab examined a fundamental question: How are physical stimuli like temperature or mechanical force translated—in a process called mechanosensation—into an electrical signal that neurons understand?
The answer lies in ion channels—specialized proteins that act as passages for ions to cross the cellular membrane. The discovery of channels that respond to mechanical pressure, called PIEZO1 and PIEZO2, was a breakthrough in sensory biology and led to Patapoutian being jointly awarded the Nobel Prize in Physiology or Medicine in 2021.
Unlike most other receptors, these channels are activated by physical forces—not chemicals. By identifying and studying these channels, Patapoutian’s team has been able to unlock new insights into the molecular basis of touch.
Implications for Chronic Pain
Pain is often more than just the result of physical damage or injury; it can arise from a complex interplay of biological and psychological factors. Recent advances in neuroscience have begun to reveal the many layers involved in experiencing pain and how this sense is modulated.
Chronic pain—defined as debilitating pain lasting more than three months—is more than a passing medical condition; it is a widespread crisis. In the U.S. alone, 20% of adults will experience chronic pain, according to the Centers for Disease Control and Prevention. Chronic pain is a leading cause of disability and has been linked to depression, higher suicide risk, substance use and misuse as well as Alzheimer’s disease and related dementias.
The standard treatment for severe pain has traditionally been opioid medications. While opioids are effective in the short term, they can lead to addiction: Hundreds of thousands of people die from opioid overdose globally each year, according to the World Health Organization. The sobering toll of this epidemic highlights the urgent need for non-addictive, safer alternatives to pain management.
While physical pain is debilitating enough, the emotional toll can be just as severe. For many people with chronic pain, the psychological impact, called affective pain—which often includes feelings of helplessness, frustration and depression—can further worsen their health. This emotional component of pain significantly impacts patients but is largely unaddressed by existing medications.
“Pain is actually a very complex, combined sensory, emotional and cognitive experience,” says Patapoutian. He envisions a future where pain can be understood, treated and even prevented at the cellular level. Just as immunotherapy transformed cancer treatment in the past two decades, pain management may be on the verge of its own transformative revolution.
Through their work on mechanosensation, Patapoutian and his team are exploring how the ion channels they discovered can be targeted to transform pain care. With a focus on molecular and cellular pathways, they aim to develop solutions that offer a safer, more effective approach to pain management beyond opioids.
For example, various stimuli (think heat, mechanical force or chemical alterations) activate a group of cells within the peripheral nervous system that send a “pain” signal to the brain. By targeting PIEZO2 and related molecules that interrupt this pathway, scientists are seeking to develop new pain treatments, especially for conditions like neuropathic pain where the sensation still exists despite a lack of stimuli.
“What’s exciting is that we now know that PIEZO2 plays a role in specific types of pain, such as tactile allodynia, where even light touch feels painful,” Patapoutian says.
As our understanding of pain deepens, so too does the potential for better treatments. By combining cutting-edge research in sensory and emotional pain, Scripps Research is paving the way for therapies that don’t just treat the problem but also address the suffering that often accompanies pain.
“Scripps Research has allowed me to build a team of scientists that’s not only diverse in expertise but also incredibly collaborative. That’s what sets us apart.”
—Ardem Patapoutian