Intercepting Pain By Fooling The Human Body | KERA News

Intercepting Pain By Fooling The Human Body

Feb 14, 2018

A team at the University of Texas at Dallas is developing a new method to treat pain by disrupting how the body processes it. 

Zachary Campbell researches pain on the molecular level at UT Dallas. His team's work describes a new method of reducing pain with RNA-based medicine. RNA stands for ribonucleic acid, which carries out genetic information from DNA to proteins.

On what causes the sensation of pain

When you have an injury, the activity of the neurons that's relevant to pain is that they generate signals that are transmitted back via the spinal cord to the brain, which ultimately will process that into some sort of behavioral output. You can imagine this as touching a hot stove and then having a jerk reflex to avoid re-injuring yourself.

DNA vs. RNA 

The blueprint that makes you you and me me is encoded by DNA. And DNA really becomes interesting after it gives birth to a molecule called RNA. Now, a particular class of RNA, called messenger RNA, transmits information to the protein synthesis machinery, which is actually compartmentalized within the cell.

So you can imagine just thinking about that process that the precise execution of that information is meticulously controlled, and you would be correct. We know that in the case of pain, protein synthesis has to occur, but we don't really understand what the targets of that event are, nor really how it's regulated.

Our goal was to just mimic one feature that is present on the vast majority of RNA with a synthetic RNA-like molecule in order to sort of decoy the factors that are involved in that regulation. It's a bit like a game of musical chairs where there are 10 people and 10 chairs. We flood the system with a thousand decoys to occupy those chairs, and so as a result the game is fundamentally different.

Zachary Campbell
Credit University of Texas at Dallas

On how the decoy molecules work

The way that they actually work, and a major challenge we had to overcome, is RNA is quite ephemeral. It's turned over rapidly on the order of hours in our hands. So we actually made molecules with the intention of changing that, that persist for over a week in serum. It's an order of magnitude more resistance to decay. What they actually do, once they binded to these factors that they're decoying, is they lead to a nonproductive sequestration. So you've essentially taken these factors out of the equation.

On addressing inflammation and other pain-associated ailments

The model that we actually use in our pain studies is called a cytokine, and this is something that's produced by the immune system to tell the neurons that there is an injury nearby. We know that we can blunt these effects of that signaling process by affecting protein synthesis within the neuron. So it is difficult to undersell the importance of the neuroimmune interface. My wife is actually a rheumatologist and so I hear about just how difficult it is to live in these conditions with persistent pain states and it's certainly something that is on my radar and that of many of the pain researchers at UT Dallas.

Dr. Zachary Campbell directs the Laboratory of RNA Control and is a professor at the University of Texas at Dallas.