Scientists have uncovered the secret behind how the common painkiller paracetamol works, potentially paving the way for pain medication with less harmful side effects to be developed.
A team from King's College London (KCL) have found that the drug, discovered in the 1890s and used widely since the 1950s, interacts with a protein found in nerve cells that was previously thought to trigger reactions to irritants like onions, mustard and even tear gas.
Despite being found in almost every medicine cupboard in the country and used commonly to treat the common cold and flu, the secret of how paracetamol works had eluded scientists until now.
They hope it will lead to the development of new drugs that have less of a risk of complications such as overdosing.
Dr David Andersson, from the Wolfson Centre for Age Related Diseases at KCL, said: "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."
The study, carried out with scientists from Lund University in Sweden and published in Nature Communications, identified that a protein called TRPA1, found on the surface of nerve cells, plays a key role in the effectiveness of paracetamol.
They found that mice which did not have the molecule present in nerve cells gained no relief from pain in lab experiments using a hot plate and the time it took the animals to remove their paws from the hot surface.
It was also found that taking paracetamol triggers the creation of harmful "break-down product" NAPQI, responsible for the toxic side effects seen following overdoses, in the spinal cord and the liver. However, they also discovered other compounds can also trigger pain relief in the spine, meaning safer drugs that work in the same way could be developed in future.