Sometimes pain is a necessary warning signal; for example, if we touch something very hot and it burns, we know to move our hand away. But chronic pain can destroy a person's quality of life, and it can be extremely challenging to get relief. Some researchers have been searching for ways to deactivate pain receptors, so the body no longer feels the neural signals of chronic pain. Using mouse models of acute inflammatory pain, scientists have shown that it is possible to deactivate pain receptors with genetic engineering tools. The work has been reported in Cell.
“What we have developed is potentially a gene therapy approach for chronic pain,” said senior study author Bryan L. Roth, MD, PhD, a distinguished professor at the University of North Carolina (UNC) School of Medicine, among other appointments. “The idea is that we could deliver this chemogenetic tool through a virus to the neurons that sense the pain. Then, you could just take an inert pill and turn those neurons off, and the pain will literally disappear.”
This study took advantage of chemogenetic technology, which was applied to the peripheral nervous system in a major breakthrough. The researchers based this effort on the hydroxycarboxylic acid receptor 2 (HCA2), which has been associated with inflammation. These receptors are only expressed in the peripheral nervous system, and they can typically bind to vitamin B3.
In this work, the scientists made alterations to HCA2 receptors so they would instead bind only to a molecule called FCH-2296413. This compound is meant to have no effect, and act only in the peripheral nervous system. The intent is to disrupt the action of pain receptors and make it more difficult for pain signals to move from sensory neurons in the peripheral nervous system to the spinal cord and brain. The mHCAD system reduces the chemical and electrical signals coming from sensory neurons, and stronger signals are then needed to cause pain to be perceived.
This was achieved using an adeno-associated virus (AAV), which infects cells not to cause harm or disease, but in this case, to deliver the therapeutic mHCAD into the proper neurons.
This study was only a proof-of-concept, and more research will be needed to show that it could be safe and effective in humans. But it is a very important step on the path to treating chronic pain in a totally new way, which aims for the pain receptors themselves.
This research is also a small part of an effort to learn more about all of the different types of neurons in the peripheral nervous system.
Sources: University of North Carolina, Cell