The Effect of Ibuprofen on the Nervous System

Ibuprofen, also known as the drugs Ipren, Ibumetin and Brufen, is a pain-relieving drug (NSAID) used for treating fever, pain and inflammation. But ibuprofen also plays a role in our nervous system, as the drug can also be used to treat pain caused by acid damage and to protect against certain types of brain damage caused by stroke. Previous studies have shown that this is due to ibuprofen’s interaction with a specific receptor – the so-called acid receptor – in the nervous system, but the nature of this interaction has hitherto been unknown.

‘For the first time we are able to give a full picture of how ibuprofen affects the acid receptor in the nervous system. We have examined in more detail the acid receptor that is activated each time we feel pain or in case of cell death, e.g. following a stroke. We have learned that ibuprofen, roughly speaking, affects the form of the receptor, preventing the signal for activating pain from being sent to the brain’, says Associate Professor Stephan Alexander Pless from the Department of Drug Design and Pharmacology, who is behind the new study.

New Technique Helps the Researchers Establish the Effect of Ibuprofen
With a view to establishing the effect of ibuprofen on the nervous system the researchers produced a series of slightly different versions of the acid receptor. Here they examined the activity in the cell before and after adding ibuprofen and minutely detailed the interaction. In the process they had to use a new method involving fluorescent substances, as the receptors are so small that they are invisible to the naked eye. But using the fluorescent technique, which makes the receptors light up, the researchers have gained further insight into the process and the movement of the receptors.

The researchers discovered that the effect of ibuprofen is caused by the receptor taking on a new form. Normally the receptor takes on a special form, which the cell recognises as pain-inducing. Then the cell sends signals to the brain and pain is felt. If ibuprofen is added, however, the receptor takes on a different form. This means that the cell is unable to recognise it as pain-inducing and therefore fails to send signals to the brain.

The Discovery Will Help Target Drugs in the Future
The researchers hope their discovery can help target and refine the development of pain-relieving drugs in the future.

‘As researchers we are constantly trying to learn and gain new knowledge on drugs and their effects. Ibuprofen is a medication used by many people, and we are therefore interested in getting the full picture of how it affects the body. For the first time we now have detailed knowledge of how it works, and naturally we hope others will be able to use this knowledge constructively in the future to develop new and more targeted drugs’, says Stephan Pless.

The study “Molecular basis for allosteric inhibition of acid-sensing ion channel 1a by ibuprofen” has just been published in the Journal of Medicinal Chemistry and is available here.

Contact:
Associate Professor Stephan Pless
E-mail: stephan.pless@sund.ku.dk
Telephone: +45 23 64 90 66