Although we know that the pain signals that move from your skin to your brain prevent your body from taking more damage than it should and let you recoil from painful situations, scientists have been unable to discover why those with chronic pain experience pain signals that keep getting sent for months and years. Now, a team of researchers from Duke University discovered the structure of a protein that is connected to the process of pain and heat perception. The protein is located in an ion channel of TRPV2, a cell surface membrane that is important for many biological processes, and could help in the development of new chronic pain therapies.
"These receptors are gaining particular attention because they are so critical to how we sense and respond to our environment," said Seok-Yong Lee, senior author of the study, in a press release. "Our results give a hint as to how one receptor works, a necessary component for developing new treatments for a variety of conditions involving sensation."
Transient Receptor Potential Vanilloid (TRPV) receptors open in response to heat, allowing calcium ions to enter and transmit a signal to the brain. Recent research unveiled the structure of TRPV1 and the current study set out to discover the structure of TRPV2 which, unlike TRPV1, is only located in the nervous system.
The team used cryo-electron microscopy, which shoots electrons at samples that either pass through it, refract or bounce back, depending on the structural characteristics of the sample, creating 2D images that were then composed into a 3D image using a computer program.
The results showed that TRPV2 represents the stage between TRPV receptor openings and closings, suggesting that it is the "in-between" state when the ion channel is desensitized to constant stimuli, which Lee believes could be used to better understand chronic pain in humans. Currently, he is trying to create the biochemical conditions necessary to push TRPV2 into other structures in order to determine what it looks like when the channel is open and closed.
"If we can obtain these different conformations, we can generate a series of snapshots - perhaps even an entire movie - that will allow us to understand how this machine operates," he said.
The findings were published in the Jan. 18 issue of Nature Structural and Molecular Biology.
