New York — The New York University College of Dentistry announced Sept. 25 that two of its researchers received a $3.9 million grant to study targeting endosomal receptors for the treatment of chronic pain.
The five-year grant, awarded by the National Institute of Dental and Craniofacial Research through the National Institutes of Health, will support Dr. Brian Schmidt, director of NYU Bluestone Center for Clinical Research, and Nigel Bunnett, Ph.D., in their collaborative research that aims to ultimately yield improved pain management without the need for opioids.
Although opioids are widely used to treat chronic pain, their efficacy is limited and their side effects are notorious; use of these drugs often leads to misuse and addiction, according to the NYU news release. Approximately 500,000 Americans died from opioid overdose over the last two decades. While many of these deaths are caused by opiates, the cycle of addiction and death is often initiated by the use of prescription drugs that were diverted from their intended purpose.
The duo’s research seeks to explore signaling mechanisms related to a family of proteins called G protein-coupled receptors, which control most disordered physiological processes, including pain, and are the target of one third of clinically used drugs. While GPCRs are thought to function at the surface of the cell, they can be subsumed within cellular organelles called endosomes. Once a GCPR enters an endosome, it is called an endosomal GPCR or eGPCR.
eGPCRs may be critical mediators of sustained neuronal excitability in the context of chronic pain. Accordingly, Drs. Bunnett and Schmidt seek to validate eGPCRs as therapeutic targets for chronic inflammatory, neuropathic and cancer pain. As part of this work they will test the hypothesis that eGPCRs generate signals in subcellular compartments of neurons that are responsible for persistent excitation and chronic pain.
“Our hypothesis — that signaling continues after a GCPR enters an endosome — breaks with the currently accepted interpretation that this process squelches signaling,” said Dr. Bunnett, who is currently the chair of the Department of Molecular Pathobiology at NYU College of Dentistry. “Many GPCR-targeted drugs have failed clinical trials, but perhaps this is because drugs should be targeting eGPCRs inside the endosome instead.”
If their hypothesis is correct, eGPCRs may be suitable targets for the treatment of chronic pain, generating a pathway for new therapies without the side effects and addiction potential of opioids.
“Our aim is to lay the foundation for the development of new types of medication beyond opioids that alleviate chronic pain including inflammatory, neuropathic and cancer pain,” said Dr. Schmidt.