The Science of Pain

Physical suffering starts at the cellular level; but what can we do to stop it?

 

The processes involved in pain are astonishingly complex. This intricacy means that combatting physical suffering can be a real challenge; but with so much on the line, it’s important that we get it right.
For that reason, a lot of work goes into investigating the science of pain. We’re already quite good at dealing with short term pain; however there is still a very serious problem with chronic pain.Whilst painkillers exist, we don’t yet know precisely how they work; this means that we’re not sure how to make them more effective or how to reduce side effects. It’s become clear that the best way to create next generation drugs is to understand biological systems at the atomic level. So instead of playing a game of trial and error, scientists now do a lot of research before they design pharmaceuticals so that they know exactly what biological element or system the new drug needs to target to be effective.

 

This new approach, known as ‘targeted drug design’, requires us to know as much as possible, right down to the atomic structure of the biological component we’re targeting. When it comes to pain, advances in scientific technology are starting to make this level of knowledge more attainable. Scientists are continuing to scrutinise the process by which pain signals are generated and transferred from the site of injury to the brain. With an in-depth knowledge of how this reaction takes place, it might be possible to design drugs that intervene at certain stages and prevent us from becoming conscious of discomfort.
 
A key element in all of this is the ion channel; this tiny cellular component looks as though it might be just the kind of target that scientists have been looking for. But to understand exactly why the channel is so important, it helps to know a bit about what pain actually is and how it works.
 
Our experience of pain results from electrical signals being sent from our nerves to our brain. When our body meets with a painful sensation, it activates the nerves, which fire off charged particles called ions. These ions then enter into the nerve cells through a hole in their surface, and it’s this microscopic hole that we refer to as the ion channel. Once through, the charged particles pass from one side of the cell membrane to the other, creating a charged current which then flows through the nerve cells. When charged with this current, the nerve cells are equipped to send electrical signals to the brain telling it that the body is in pain.
 
So this is why the ion channel is such a key piece of the puzzle; because it is here that the current is generated to fire electrical signals to the brain. If scientists can find a way to close the channel and block the entry of charged particles into the cell membrane, then they can prevent electrical current being generated and stop those messages being sent on.
 
Until recently though, there was a problem: we didn’t actually know that much about the structure of the ion channel. Prof Liz Carpenter and her team from the University of Oxford have changed all that. The group has been using four of Diamond’s macromolecular crystallography beamlines – I02, I03, I04, and I24 – to study the channels. Although there are lots of channels, all responsible for processing different stimuli, Liz’s group were particularly focussed on a channel called TREK-2 which is one of the channels that is strongly linked to the pain response.


Using X-ray crystallography, Liz and her team were able to get atomic images of the ion channel in both an open and closed position. They were even able to capture an image of the channel with Prozac bound to it. Prozac is an antidepressant and is not designed to interact with this protein, so it binds very weakly. But by chemically modifying the drug, the team could potentially improve binding and blocking of the channel, thus opening up new avenues for the design of next-generation painkillers.

This is an exciting moment for research into pain and pain visualisation. Thanks to Diamond’s bright beams and the bright minds behind them, we now have an atomic picture of how this ion channel is structured. That brings us one giant leap closer towards developing drugs that can hook into the nooks and crannies of the channel and keep it firmly closed.

But Liz and the team aren’t done yet; they now want to move on to decoding other ion channels, some of which are responsible for migraine and a host of genetic diseases. It seems that these tiny cellular elements have a big impact on our lives, helping to determine how we sense the world around us. The work of Liz and her team provides a vital framework that scientists can build on. Because of them, we know what the target looks like; now we just need to take aim and fire.

 

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