Preventing pain

26 June 2011

Interview with

Professor John Wood, University College London

Katrina -   Pain is a huge problem and one that current drugs often fail to answer.  To find new ways of blocking pain, scientists are investigating the pain pathway from start to finish - from the tips of our fingers to the depths of our brains.  I spoke to John Wood who is Professor of Molecular Neurobiology at University College London.  He's one of the leading scientists involved in looking for new ways to interfere with pain.

John -   So what happens when you treat joint pain or have some acute pain episode is that there are specialised nerves that innervate all parts of the body - the skin, the muscle, the viscera -- and they've all got various receptors on them that respond to chemicals released from damaged tissue.  What will happen is that you'll damage the skin and then some chemicals will activate these sensory nerves and they'll then send an electrical signal into the spinal cord which will activate further neurons up into the forebrain, the cortex, where pain will eventually be perceived.

Katrina -   So scientists are beginning to understand the processes involved in sensing pain, but we're still far from conquering this unpleasant sensation with drugs.

John -   It's true that we're still dependent upon drugs that have been around for many centuries. Opioid drugs and non-steroidal anti-inflammatory drugs. Aspirin-like drugs are the main stays.  We are limited however by the side effect problems of a number of quite potent drugs.  I think the estimate is something like 6% of the population are suffering from some quite severe ongoing chronic pain which isn't adequately treated at the moment.  That translates into 2 or 3 million people in the United Kingdom who are very poorly treated for ongoing pain as we speak.

Katrina -   This may be about to change.  New advances in techniques to analyse people's genetics may hold the key.

AspirinJohn::  Yeah, that's true.  It's been quite wonderful - the payoff that's come from sequencing the human genome. It is now possible to get the complete sequence of all the DNA that encodes proteins in a person for about £1,000.  It's become terribly straightforward to map mutations which may underlie various pathological conditions including unusual pain states.  So, we've been looking around for people with extreme pain syndromes- heritable families which have got either a loss or a gain of pain syndromes.  We can then find genes that are obviously significant in terms of normal pain sensation by identifying the mutations that underlie these kinds of pain conditions.

Katrina -   So in order to block pain with effective drugs, we'll need to understand the proteins needed for pain sensation.

John -   Genetic studies of people who have a loss of pain sensation have highlighted two different sets of proteins. The first are trophic factors, proteins that are involved in the development of the sensory nerves when you are growing up, even in the uterus.  The second set of proteins are the ion channels that are responsible for the electrical signalling that goes on in these cells which are responsible for sending information into the brain that tissue damage has occurred.  The two best examples in this area are firstly the trkA Receptor, which is a trophic factor receptor.  If you have a mutation in that which stops it working, you don't have any sensory nerves. Secondly is the SCN9A ion channel which is responsible for electrical signalling, particularly in those damaged sensory neurons that cause you to feel pain.

Katrina -   Studying people with rare genetic conditions that cause abnormal pain sensation may provide scientists with the information that they need to treat people with any type of pain.

John -   Probably the best example comes from a research group in Cambridge led by Professor Geoffrey Woods. He found a gene called SCN9A which is lost in various families that are pain free.  This SCN9A gene makes a protein which is called a sodium channel.  This is responsible for the electrical signalling in the sensory nerves that we were discussing earlier.  So what you can now do is you can take this protein, you can make it in cells, and you can then screen drugs that block its activity.  This is what the major pharmaceutical companies have been doing over the last 5 years or so and fortunately, there do seem to be some quite potent new drugs coming up that block this gene product which are effective painkilling drugs.  So this is hugely exciting and over the next 5 to 7 years, we hope that some of these compounds will become available in the clinic and will actually be useful additions to the present set of drugs that we can use to treat pain.

Katrina -   So the gene identified by Geoffrey Woods' lab is a great example of a potential drug target.

John -   Well SCN9A is a very interesting gene because it's been linked to both loss of pain sensation and in some unusual syndromes for people that have ongoing pain.  When the gene was sequenced we found out what it actually does and how it's working. It encodes a protein that's involved in electrical signalling.  The people that suffer ongoing pain as a result of mutations in this gene have a hyperactive protein. It sends electrical signals into the brain at a very high frequency in response to fairly low level damaging stimuli, whereas people that have got a loss of function of this protein, so that it doesn't work at all, are unable to feel any pain. Interestingly they can't smell because this protein also has a role to play in the olfactory epithelia.  This of course gives us a wonderful clue into a potential route to developing new painkilling drugs that act on this gene product.

Katrina -   Every day, scientists are stepping closer to conquering pain, but John Wood offers a word of caution.

John -   Pain is both a friend and foe because if you're born with a pain-free condition, you have terrible problems injuring yourself all the time.  Pain does teach us to protect ourselves and we don't really want to abolish acute pain.  What we really want to do is to normalise pain thresholds so that people with things like rheumatoid arthritis or osteoarthritis just have normal levels of pain and are able to sense damaging stimuli, but don't have that ongoing chronic pain which makes their lives a misery.  We're making progress both in immunology and in sensory neurobiology in understanding these kind of mechanisms. I'm really actually very optimistic that new drugs will be coming through the next few years that will treat these conditions relatively effectively.

Katrina -   That was Professor John Wood from University College London.

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