$2.4 Million Grant Funds Collaboration to Study Nerve Cell Receptors Responsible for Chronic Pain

Nigel Bunnett and Brian Schmidt
Dr. Nigel Bunnett (left) and Dr. Brian Schmidt (right)

The Department of Defense (DoD) has awarded Brian Schmidt, DDS, MD, PhD, director of the Bluestone Center for Clinical Research at New York University College of Dentistry (NYU Dentistry) and Nigel Bunnett, PhD, professor in the Departments of Surgery and Pharmacology at Columbia University, a joint $2.4 million, three-year grant to study how receptors inside nerve cells generate chronic (long-lasting) pain. Three painful medical conditions prevalent in military personnel and veterans—headache, nerve injury, and infectious colitis—will be investigated.

Knowledge gleaned from this work has broad implications beyond the military and will be used to develop new treatments for chronic pain. Chronic pain management is an immense problem, with one in five people suffering from chronic pain during their lifetime.  This type of pain is a major cause of human suffering because opioids and other classes of medications are ineffective. Opioid effectiveness wanes with extended use; larger doses are required as opioid tolerance develops. Current treatments for chronic pain also generate debilitating side effects including profound sedation and addiction. The opioid epidemic highlights some of the problems associated with these drugs.

Drs. Schmidt and Bunnett will investigate receptors on and within nerve cells. Pain-sensing nerve cells are covered with receptors that react to painful stimuli. These receptors can detect many substances that are produced by injured tissues and some types of cancer. One pain-relieving strategy involves blocking the activity of the receptors positioned on the surface of pain-sensing nerves. Bunnett discovered that chronic pain can develop when activated receptors on the cell surface are endocytosed (internalized within the cell) or when endocytosed receptors are activated internally by endocytosed pain mediators.

“Conventional drugs do not penetrate nerves and thus cannot effectively inhibit endocytosed receptors,” says Bunnett. “Drugs that inhibit receptors inside nerve cells, rather than on the cell surface, might provide superior and long-lasting pain relief.”

Patients diagnosed with painful forms of cancer or with chronic pain may benefit from Schmidt’s and Bunnett’s findings. “Our nerve receptor research has potentially groundbreaking clinical applications,” says Schmidt. “This work could define a new class of drugs for chronic pain treatment – non-addictive drugs that produce fewer deleterious side effects.”

Bunnett notes that the research also has important implications beyond the treatment of pain. “Hundreds of members of this receptor family are found on all cells; a third of all clinically-used drugs act on these receptors. The knowledge derived from our work might be useful for modification of existing drugs used to treat a wide variety of diseases including heart disease and cancer.”

This work is supported by The Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense under Award Nos. W81XWH1810432 (NYU) and W81XWH1810431 (Columbia). Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

About the Bluestone Center for Clinical Research
The Bluestone Center for Clinical Research, in conjunction with the NYU Oral Cancer Center, is an academic research organization located at the NYU Dentistry. Bluestone's mission is to take a creative scientific approach to transform world health. Investigators at Bluestone Center conduct research on oral cancer, cancer symptomatology, pharmaceuticals, medical devices, emerging biotechnology, periodontics, implants, and oral health products.

About NYU College of Dentistry
Founded in 1865, NYU Dentistry is the third oldest and the largest dental school in the US, educating nearly 10 percent of all dentists. NYU Dentistry has a significant global reach with a highly diverse student body. Visit http://dental.nyu.edu for more.