For millions of people around the world, pain medications offer a chance for comfort and respite. However, these medications don’t always work and can occasionally lead to a dangerous cycle of misuse and addiction. 

The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage.”. When our bodies are exposed to a harmful stimulus, sensory neurons called nociceptors detect the pain and send signals through our spinal cord and to our brains. The human brain receives and recognizes the sensation as pain. 

Pain can be classified as acute—lasting up to one month—or as chronic—lasting more than three months. In 2023, the Centers for Disease Control and Prevention reported that 24.3% of adults have chronic pain and that pain increases with age. Doctors frequently prescribe opioid medications to treat acute-to-chronic pain; however, opioids often lead to forms of addiction. 

Scientists under the NIH Helping to End Addiction Long-Term (HEAL) Initiative have investigated druggable cellular targets that could provide non-addictive alternatives to opioids. In past years, researchers have focused on Nav1.7, one of our bodies’ voltage-gated sodium channels. Nine different types of Nav channels exist across our bodies and function as proteins that open and allow sodium ions to pass through in response to voltage changes. Nav1.7 detects and communicates pain through our nerves. Nav1.7 was first identified as a potential drug target through genetic studies of people with Congenital Pain Insensitivity, a rare condition in which individuals cannot feel pain due to their inoperative Nav1.7. Thus, by blocking Nav1.7 activity, researchers aim to minimize pain transmission in our bodies. However, attempting to block these channels without affecting other bodily functions, like breathing, may prove difficult. 

Led by Dr. John Mulcahy, a team at SiteOne Therapeutics has identified inhibitors that can block the activity of the Nav1.7 protein. The inhibitors are intended to mimic the lack of pain sensation that is present in those with malfunctioning Nav1.7 channels. Throughout animal studies and a collaboration with Vertex Pharmaceuticals, this research group is exploring Nav1.7 as a potential therapeutic target. 

Dr. Joshua Rosenthal and his team at the Marine Biology Laboratory at Woods Hole have taken a different approach: toning down Nav1.7 activity in cells that already produce Nav1.7. Dr. Rosenthal and his colleagues hope to minimize pain signals by editing Nav1.7 mRNA to produce Nav1.7 proteins that are less functional and therefore lead to reduced pain sensation.

Above: Researchers are currently investigating multiple strategies to decrease Nav1.7 activity and mitigate chronic pain. Image courtesy of the NIH.

A third approach led by Dr. Ana Moreno and her team at Navega Therapeutics attempts to switch off Nav1.7 using epigenetic modulation. This method would give the DNA the ability to turn Nav1.7 “on” and “off” when needed. Moreno’s team is testing the use of gene therapy to modify Nav1.7 in animals and is working to find a similar solution to test for human cells. 

Ultimately, Nav1.7 targeting requires further study to provide a non-addictive alternative for pain medication. While teams are still working through a variety of projects to find the best solution and mitigate side effects, the diversity of approaches through the NIH HEAL Initiative demonstrates an encouraging solution to the future of pain treatment.‍

Written by Ella Kotelanski, this article was selected as a winner of our 2025 High School Science Communication Challenge. From Bethesda, Maryland, Kotelanski is a student at Walt Whitman High School.

‍