Less harmful pain relief on the way as researchers work out how paracetamol works
A team of researchers has discovered how one of the most common household painkillers works, meaning pain relief medication with less harmful side effects could soon be a reality. Presenting their findings in the journal Nature Communications, the researchers, from France, Sweden and the United Kingdom, explain how paracetamol, one of the most used drugs in the world, actually works. Although paracetamol was first discovered in the 1890s and has been marketed as an over-the-counter painkiller since the 1950s, exactly how it relieves pain has remained unknown - until now. In a groundbreaking finding, the team determined that a protein called TRPA1, found on the surface of nerve cells, is a key molecule needed for paracetamol to be an effective painkiller. One of the study authors, Dr David Andersson from King's College London says: 'This is an extremely exciting finding, which unlocks the secrets of one of the most widely-used medicines, and one which could impact hugely on the development of new pain relief drugs. Paracetamol is the go-to medicine for treating common aches and pains, but if the recommended dose is significantly exceeded it can lead to fatal complications. So now we understand the underlying principal mechanism behind how this drug works, we can start to look for molecules that work in the same way to effectively relieve pain, but are less toxic and will not lead to serious complications following overdose.' Recent studies have shown that taking too much paracetamol on a regular basis puts patients at high risk of an accidental overdose which can have fatal consequences. As well as being a widely used painkiller in its pure form, it is also the main ingredient in everyday medications such as cold and flu remedies. The team of researchers used a 'hot-plate' test to observe the effects of paracetamol in mice. This involved measuring the number of seconds it takes for a mouse to withdraw its paw from a slightly hot surface. They found that paracetamol increased the time it took for mice to withdraw their paw, showing that the drug reduced the heat-induced pain. The scientists then carried out experiments to observe what happened when the TRPA1 protein was not present at all in the mice. They found that when they removed the TRPA1 protein and repeated the hot-plate test, the paracetamol had no pain-reducing effect. This showed them that the protein is a key molecule needed for paracetamol to be an effective painkiller. Professor Bevan, another author on the study and also from King's College London comments: 'These results are surprising because previous studies have shown that TRPA1 can actually produce pain, coughs and hypersensitivities -- it is the receptor for many common irritants like onion, mustard and tear gas. So our discovery shows for the first time that the opposite is in fact true -- this protein is a novel mechanism of action for a painkiller.' The team also discovered that taking paracetamol triggers the creation of the harmful 'break-down product' NAPQI, responsible for the toxic side effects seen following overdoses, in the spinal cord and the liver. Thankfully, their findings also showed that other compounds can also trigger pain relief in the spine, meaning safer drugs that work in the same way could be developed in the future. If the team can now identify other painkilling compounds similar to paracetamol that use the same TRPA1 pathway to prevent pain signals sent by nerve cells to the brain, it is possible that they can find a compound that does not have toxic effects and can reduce the risk of overdose. The publication of this study therefore acts as the green light for TRPA1 to be used as a new target for pain relief drugs as Dr David Andersson explains: 'Many targets have been identified in the past, but as paracetamol is a medicine that we know works well in humans, this gives us a head-start in looking for effective molecules that utilise the same pathways but are less harmful.'For more information, please visit:King's College London:http://www.kcl.ac.uk/index.aspx
Countries
France, Sweden, United Kingdom