Paracetamol is the active ingredient in many common pain relief drugs. Those who use the drugs correctly are not at risk, but those who overdose or take them with alcohol could suffer liver damage.
Paracetamol poisoning in teenagers is a major problem, according to the Swedish Medical Products Agency. Large overdoses in connection with suicide attempts can cause serious liver damage and death, and a liver transplant is sometimes needed to save the life of the patient following paracetamol poisoning. Whereas other drugs are usually developed into new products that are more effective and have fewer side effects, this has not happened with paracetamol.
“Many attempts have been made, but none has succeeded. When the molecule has been altered to remove its harmful effect on the liver, the pain relieving effect has also been lost”, explains Professor Edward Högestätt.
He and his colleague, Reader Peter Zygmunt from the Division of Clinical Chemistry and Pharmacology, have carried out research on pain using flavours like garlic, chilli and wasabi mustard. These seasonings taste completely different but can all produce unpleasant effects: if you eat too much you get a burning sensation in the mouth and may experience redness and swelling. This is because these substances affect nerves that form part of the pain system.
Edward Högestätt and Peter Zygmunt have studied one of the products to which paracetamol is broken down in the body – the product that is believed to be responsible for the liver damage. They have found that this substance activates the ‘garlic receptor’ in the spinal cord. This receptor has the ability to stop the signals in the pain-sensing nerves, which has a pain-relieving effect.
“It is exactly the same substance that is responsible for both the liver damage and the pain relief. This explains why it has not been possible to separate the two effects”, says Edward Högestätt.
Now that the researchers have understood which receptor is activated, they have been able to tailor-make a harmless molecule that affects this exact receptor. It is a cannabinoid, i.e. a substance from the cannabis plant.
“However, this substance has no narcotic properties”, emphasises Peter Zygmunt. He therefore hopes that this substance, or another harmless substance that affects the garlic receptor, could be developed into a harmless yet effective pain-relieving drug.
The researchers’ findings have been published in the new online journal Nature Communications.