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Friday, 30 August 2013

Magical Sunburn Medicines courtesy of TRPV4

28th August 2013
There was a lot of recent coverage of a paper claiming that a particular protein called "TRPV4" causes the pain of sunburn. It has been floated that this could allow us to magic up some really great sunburn relief creams and hugely increasing Q.O.L ... Quality Of Life!!
What I was hoping to do in the blog is discuss (1) why this is not such a good thing! .... (2) why I say they "claim" rather than "show", (3) what the TRPV4 protein is, and finally da da da da daaaaaaa (4) Exerimental treatments.
Why is this new discovery a bad thing?
OK chronic pain... I.e., pain which goes on for weeks, months and years is a terrible thing, and we think of this as a disease in itself. Acute pain is rather different; in some cases it is awful, but frequently it is a really effective warning that something is awry and needs to be sorted. People who lack pain sensing ability have a dreadful time, they injure themselves left right and centre and just don't know until serious harm has been done. There are animals which lack pain sensing for particular types of pain when it suits their lifestyles, but for the rest of us it's a protective mechanism to stop us injuring ourselves. So in this case, not only does the sun age your skin, but it really does, unambiguously give you cancer. The more you can tolerate being burnt, presumably the more you will allow yourself to be burnt and the more likely you are to get cancer.
As for pain relief; in theory morphine like drugs and local anaesthetics would already stop the pain if that was all you wished to do. Morphine is considered too dangerous, and local anaesthetics, basically inappropriate. Obviously you should speak to your pharmacist of GP about treatment, but generally they'll say moisturising creams will feel nice and some ibuprofen-like drugs or paracetamol (acetaminophen) may help... a bit.

Why did I say "claim", rather than "show"?
I really hate "scientists have shown" on the news. What they should say is Dr Fred blogs and colleagues have shown... Or possibly "a new research a paper shows". Frequently, these days the truth would be "a University Public Relations press release says"..... Anyway in this case it was a research paper that the information was published. The Journal is called the Proceedings if the National Academy of Sciences (PNAS).
Well it is no suprise that TRPV4 would be involved, it is found all over the body and important for all sorts of things, but there is always scope for skepticism with this type of report. It was published in the journal PNAS, which has an excellent reputation although it has an unusual procedure for selection and review of scientific papers. Some people have raised objections to this. Secondly, there is a tendency for people to always find the particular protein they work on to be the lynchpin of whatever system they happen to work on ;-)
In fact my own colleagues and I were looking at a different protein that seemed important. They don't have to be mutually exlusive though. There are probably many proteins which are involved in sunburn pain.
TRPV4 is likely to be involved however, because it is a protein which is important to sensing much of the normal mechanical (touch) stimulation of the skin. In sunburn we have an oversensitivity to touch, therefore, it stands to reason that if you loose the ability to sense touch, you will also loose the sunburn induced oversensitivity!
What is the TRPV4 protein?
This is top dead centre my area of research. I'd like to step back and remind people that we are, as animals, mostly chemicals and electricity. Now I am sure many people know this, but if you don't its going to sound like sci-fi, but it really is known quite well. All nerves that either transmit senses like touch, pain or pleasure are effectively electric wires. Electric current flows through them like wires running between a switch and a light. The voltage is about a thousandth that of a domestic light, or a hundredth of a modern torch. TRPV4 is a type of protein called an "ion channel" which acts to generate this voltage... An ion channel has two parts conceptually, a battery and a switch. In th case of TRPV4, the sunburn throws the switch thus stimulating the nerve cells which conduct the pain to the brain. In fact this "ion channel" can be activated by all sorts of other things too... Including pressure and some drugs/chemicals. The problem with it, a drug target though, is it really is found so widely throughout the body... Side effects could be a real problem.

Some experimente to see if its true?
I think not! There are a number of chemicals known which inhibit the action of TPRV4 already. Therefore they should prevent the pain of sunburn. It would be irresponsible of me to list them here, but they are no doubt, findable with some Googling. Presumably they would reduce the pain of sunburn. Most of these compounds are expensive and pretty deadly. TRPV4 is found all over the body, so you'd not just loose the sunburn, your kidney would not work properly, your joints would be affected, you'd feel numbness and loose control of your blood pressure. So direct application to the skin? Unfortunately, they tend either to not penetrate the skin, or they do absorb nicely, but they give you cancer :-(
Personally, waiting it out or using paracetamol seems a better idea to me.

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