Chronic pain is one of the most challenging medical conditions for people to live with. “It takes people’s lives away from them, even though it doesn’t kill them,” says William Renthal, M.D., Ph.D., Director of Research at the John R. Graham Headache Center at Brigham and Women’s Hospital in Boston.

Renthal knows firsthand the impact pain can have on people’s lives and how difficult it is to treat, as both his wife and his daughter have chronic migraine. Their experience inspires his research into better ways to understand and treat pain.

Renthal also is Director of the Harvard PRECISION Pain Center, one of five centers in the PRECISION Human Pain Network, which is funded by the National Institute of Neurological Disorders and Stroke through the Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®. The center’s researchers are using cutting-edge technologies for large-scale discovery of human pain-associated genes and to analyze the specialized nerve cells (nociceptors) that detect and transmit pain signals to the brain. The researchers want to understand how transmission of pain signals alters the cells’ activity and, in particular, how these cells and their expression of pain genes may differ between people with and without pain.

Renthal and his team are using a range of advanced technologies that can analyze genes and molecules even in individual cells. With these approaches, they are cataloging all the genes, proteins, and other relevant molecules that are active in these pain-sensing cells and thereby contribute to the unique ability of these cells to detect and transmit painful signals to the brain.

The next step is to compare this molecular inventory between cells from people with and without chronic pain. Which genes are active, which genes are turned off in the specialized nerve cells, and how does that influence pain signal detection and transmission properties of these cells when a person experiences chronic pain? What makes nerve cells that trigger chronic pain unique?

“We’ve only understood these cells and genes in animals, and we don’t actually understand what is going on in people,” Renthal explains. His research hopes to change that.

The benefits of this research could go far beyond knowing more. Pinpointing genes or proteins specific to chronic pain-sensing cells could help identify potential targets for new, highly specific pain therapies. Furthermore, these discoveries could open the path forward to personalized pain therapy.

“We currently don’t have pain medications that are free of side effects,” says Renthal. More specifically targeted medications likely won’t affect, for example, nerve cells that control breathing or increase the risk of addiction the way opioid pain medications do. Such targeted approaches could bring safe and reliable relief to many of the millions of Americans with chronic pain.

Watch Renthal’s full video interview.

Harvard PRECISION Human Pain Center

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