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How paracetamol really works

18.6.2025

Translation: machine translated

Paracetamol has been used to treat pain for decades. Until now, it was thought to act primarily in the brain and spinal cord, but the decisive pain relief takes place much earlier.

Paracetamol is one of the best-known painkillers, but exactly how it relieves pain is not yet fully understood. Until now, it was assumed that the drug only worked in the central nervous system, i.e. in the brain and spinal cord. However, according to a study by the Hebrew University of Jerusalem it also specifically blocks pain where it arises.

The researchers were able to show that after taking paracetamol, the intermediate product 4-aminophenol is initially produced in the liver. This enters the brain and the peripheral nervous system via the bloodstream. There, the body's own enzyme FAAH converts the substance into the degradation product AM404.

Although it is known that AM404 mediates the effect of paracetamol, it was unclear exactly how it contributes to pain relief. It was assumed that the substance acts on cannabinoid receptors in neurons of the central nervous system. The new study shows that AM404 is also produced directly in the peripheral nerve endings that perceive pain stimuli. It blocks two specific sodium channels in the pain-sensitive neurones that normally transmit the corresponding signals to the spinal cord. The pain is therefore combated at its source.

In animal experiments, the researchers were able to demonstrate this mechanism in both acute and inflammation-induced pain. The effect is mechanically similar to that of local anaesthetics, but is more selective. The authors write that the findings on AM404 therefore open up new approaches for more precise painkillers with fewer side effects.

Spectrum of science

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Originalartikel auf Spektrum.de

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