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Blueprint Of Protein Linked To Pain, Heat Perception May Lead To Better Chronic Pain Treatment

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Researchers have found an ion-channel protein structure located in the cell's surface membrane. Apart from the detection of heat, this protein structure could lead to new ways of understanding and treating chronic pain.

For example, when you accidentally touch a hot object, you instantly withdraw because the skin's sensors have interpreted the heat and have sent signals to the brain, prompting you to let go before sustaining serious injuries.

Unfortunately, for people suffering from chronic pain, the pain and signal are continuously felt even in the absence of an actual, clear cause.

The study was published in the journal Nature Structural Biology and Molecular Biology on Monday. The findings could lead to new treatments that can attack pain receptors. Currently, chronic pain is often underdiagnosed, sometimes even poorly managed. Severe or chronic pain affects over 100 million Americans to date.

Senior author of the study, Seok-Yong Lee, Ph.D., said that these pain receptors play critical roles in how people detect and react to environmental elements. Lee is a biochemistry assistant professor from Duke University School of Medicine.

"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," said Lee.

Cell membranes house a number of ion channels that act as information gatekeepers. In the Transient Receptor Potential Vanilloid (TRPV, pronounced trip-vee), the information transforms into calcium ions.

Similar to when a valve is turned on, TRPV receptors open when it detects harmful heat or some other stimuli. When opened, the calcium ions flow and send signals to the brain through the nervous system. Lee and his team created a structural representation of how these receptors open and close, which resulted in a blueprint that can help design better drugs targeting the ion channels.

In the past research, they were able to create the schematic of the first protein TRPV1, which is only present in the nervous system. In the current study, the team worked on the second protein TRPV2, which can be found through the human body.

The team used a technique called cryo-electron microscopy to create the protein's blueprint. This technique requires dispersing and stabilizing the protein in a solution before the "flash frozen" protein can be visualized.

The teams compared the two protein structures, and found that the TRPV2 structure is very far from the open and closed blueprints of TRPV1.

They found that TRPV2 has a third, in-between stage where the channel becomes numb or frozen when presented with a recurrent stimuli. The team believes that studying this desensitized stage could lead to the treatment of chronic pain.

Moreover, the researchers were able to link the protein structure with the maintenance of a strong heart, prompting the death of cells in specific cancers and aiding in the disposal of pathogens, which are somehow dissimilar biological processes.

The team is now developing several biochemical settings to force TRPV2 into other shapes. This will help Lee and his team to map out when the structure is open or closed. The team also hopes to determine the structures of other proteins within the TRPV family.

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