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First study to reveal how paracetamol works could lead to less harmful pain relief medicines
Date:11/22/2011

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 a protein called TRPA1 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 analgesic effect. This identifies the protein as a key molecule needed for paracetamol to be an effective painkiller.

However, paracetamol on its own does not activate the TRPA1 protein. The study showed that when paracetamol is administered, a break-down product called NAPQI is formed in the spinal cord (where 'painful' information is processed). This product is also formed in the liver and is responsible for the toxic side effects seen following overdoses.

Furthermore, they demonstrated that other compounds that, unlike NAPQI, are not toxic can activate TPRA1 in the spinal cord when injected into mice. Because these compounds are not reactive, they are less likely to be harmful.

Professor Stuart Bevan, co-author from King's, said: 'What we saw happening in the mice was that the break-down product formed from paracetamol in turn stimulates a protein found on the surface of nerve cells called TRPA1. When this protein was activated, it appeared to interfere with the transmission of information from that nerve cell to other nerve cells, which would normally send a signal up to the brain, signalling pain. So in this case the NAPQI product that was formed from paracetamol acted on the TRPA1 protein to reduce transmission of information from pain-sensing nerves to the brain.

'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 ac
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Contact: Katherine Barnes
katherine.barnes@kcl.ac.uk
44-020-784-83076
King's College London
Source:Eurekalert

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