25 February 2014

Hope for better treatment of chronic pain


An international researcher is on the trail of how to alleviate chronic pain after receiving a fellowship of 10 million DKK from the Lundbeck Foundation.

Associate Professor Stephan Pless, an expert in the study of cell membrane receptors will be moving his research from the University of British Columbia to the University of Copenhagen.  In particular, his research will focus on a receptor called P2X, which in recent years has received increased attention in pain research.

Zooming in on pain receptors

Scientists have shown that the P2X receptor plays a role in many diseases that involve chronic pain. However, many details about the receptor are still scientifically unknown. The goal of the 5 year research project is to provide a detailed account of how P2X receptors work and how they may be manipulated.

The P2X receptor consists of three large molecules, proteins, which change form depending on the state of the receptor. In this way, P2X opens and closes a so-called ion channel, which allows electrically charged particles to flow in and out of the cell.

“I want to find out how the P2X receptor changes its structure between different states. Because, when the receptor keeps its ion channel constantly open, it can lead to chronic pain in patients,” he says.

Stephan Pless

Stephan Pless.

Illuminating the receptor with fluorescent amino acids

The P2X receptor is too small to study directly in a microscope. Therefore, Stephan Pless uses a range of advanced techniques that are well suited to reveal how the receptor changes its state. For instance, he replaces some of the amino acids in the receptor with artificial amino acids that do not exist in nature. The artificial amino acids slightly alter the receptor’s mechanism, revealing how it is built and how it binds to signal molecules or drugs.

In addition, he uses fluorescent amino acids in his research. When irradiated, these amino acids light up with varying intensity, depending on the state of the receptor. In this way, further knowledge about the receptor mechanism can be gained.

Aim: New drugs for pain-afflicted patients

Better insight into the receptor’s structure and function will help researchers design drug compounds that can regulate the P2X receptor. Compounds that could block the receptor are already being tested. However, as it is not yet clear how these compounds bind to the receptor molecule, scientists do not fully understand how they function. Stephan Pless is hoping his research will create greater understanding of how the molecule works which could lead to better types of drugs for patients with chronic pain.


Stephan Pless
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