Paracetamol pathway revealed
1 Dec 2011 by Evoluted New Media
We all reach for the paracetamol to ease our aches and pains, but exactly how the analgesic relieves our pain was a mystery. Now researchers from King’s College London have now uncovered the drug’s principal mechanism of action. The research, which included researchers from Lund University in Sweden, found that TRPA1 – a protein found on the surface on nerve cells – is needed for paracetamol to be an effective painkiller. However, paracetamol alone does not activate TRPA1, as other compounds can also activate the protein when injected into the spinal cord.
“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,” said Dr David Anderson from the Wolfson Centre for Age Related Diseases at King’s.
Researchers used a hot-plate test to observe the effect of paracetamol in mice, measuring the number of seconds it took for the mouse to withdraw its paw from a slightly hot surface. They found paracetamol increases the time it took for withdrawal.
They then carried out the experiments in mice lacking TRPA1 and found that paracetamol had no effect, suggesting TRPA1 is a key molecule needed for paracetamol to become an effective pain killer.
“These results are surprising because previous studies have shown that TRPA1 can actually produce pain, coughs and hypersensitivities,” said Professor Stuart Bevan, who led the research. “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 study showed that when paracetamol is administered, a breakdown product called NAPQI is formed in the spinal cord, where pain information is processed. This product is also formed in the liver and is responsible for the toxic side effects seen in overdose patients.
Researchers hope that by identifying other analgesic compounds similar to paracetamol that use the same TRPA1 pathway to prevent pain signals being sent by nerve cells to the brain, they may be able to find a compound that has no toxic effects and will reduce the risk of overdose.
