NYU Pain Research Center Receives NIH Grant to Study Chemotherapy-Related Pain

10/3/24

The National Institutes of Health has awarded a five-year, $4.63 million grant to NYU College of Dentistry researchers to study chemotherapy-induced painful peripheral neuropathy (CIPPN). The funding is part of the NIH’s Helping to End Addiction Long-term (HEAL) Initiative, which supports the development of safe and effective therapeutics to treat pain in an effort to end the opioid crisis.

CIPPN is a common side effect of cancer treatment that causes significant pain and affects patients' quality of life. This condition often forces doctors to reduce or stop chemotherapy, which can harm the success of cancer treatment. The main issues causing CIPPN include damage to mitochondria (the cell's powerhouses), oxidative stress, and chronic inflammation. These lead to the over-sensitization of nerves, resulting in chronic pain. Unfortunately, there are no effective therapies to prevent or treat this condition.

While most studies have looked at how sensory nerves contribute to this pain, recent research highlights the importance of Schwann cells—a type of glial cell that is capable of sensing external noxious stimulations and supports nerve cell structure and function. Schwann cells are highly sensitive to chemotherapy but their role in CIPPN isn't well understood. The researchers in this study will investigate two key proteins involved in the survival and function of Schwann cells that can be targeted to protect these cells from chemotherapy damage, reduce inflammation, and prevent the nerve over-sensitization that leads to pain.

The study is led by Drs. Yi Ye at NYU Pain Research Center and Wendy Campana at University of California San Diego. The research team also combines collaborative and multidisciplinary efforts from Drs. Brian Schmidt and Bradley Aouizerat at NYU College of Dentistry, Gulchin Pekkurnaz from University of California San Diego, Rajesh Khanna at University of Florida, and Sascha Alles and Reza Ehsanian at University of New Mexico. Collectively, the team will undertake experiments in cell culture systems, mouse models, and tissues from cancer patients and organ donors using a combination of behavior, genetics, pharmacology, electrophysiology, fluorescence and electron microscopic imaging, bioenergetics, and bioinformatics tools.

“Our hope is to not only establish Schwann cells as a major contributor to chemotherapy-induced painful peripheral neuropathy, but to also investigate how the cells can be targeted for treating this painful condition,” said Dr. Ye.

This project (grant number R01DE033674), titled “Targeting Schwann cell dysfunction and repair signaling in chemotherapy induced painful peripheral neuropathy,” will take place over two phases. The first phase began in September 2024 and will conclude in August 2027, with a total funding amount of $2,833,086. The second phase is two years from September 2027-2029 with a total funding amount of $1,795,793.