How do over the counter pain-relievers work?

“…How are they are effective for so many different types of pain coming from different parts of the body to the brain?”

Pills by Grumpy-Puddin, on FlickrThe three most popular types of over-the-counter pain relievers are aspirin, ibuprofen and paracetamol (acetaminophen). They work in different ways and to understand how they work, we need to first take a quick look at why we feel pain in the first place.

Pain is felt whenever something activates our pain receptors – nerves that are designed to detect damage or the threat of damage. A pain-causing stimulus could be something directly touching us or it could be a chemical (chilli-peppers, anyone?). Whichever it is, the pain fibre transmits an impulse, which travels to the spinal cord and then onwards to the brain (equalling ‘ouch!’). It’s not just electrical signals though; damage – such as a cut to the skin – also releases substances to the surrounding area. These include, among others, substances called prostaglandins. Prostaglandins act on the pain receptors, making them more sensitive. (Ever noticed how it hurts whenever you touch near an injury? Well, now you know why.) Evolutionarily, this is important as it means we protect injured areas, due to the increased tenderness, until they are properly healed.

Aspirin and ibuprofen work in a similar way: they stop the tenderness-causing prostaglandins from being produced. (They actually stop a protein called cyclooxygenase-2 (COX-2) from working. COX-2 is needed to produce prostaglandins so by inhibiting it, the area will stop being as sensitive.)

Paracetamol works on the brain and spinal cord… possibly. To be honest, no one really knows how it works although we’ve got some good ideas*.

Another type of painkiller that is more powerful than these three is codeine. It works in a slightly different way again. Codeine blocks the transmission of pain signals from passing through the brain and spinal cord. It is a type of drug called an ‘opioid’ and works by mimicking the body’s natural pain-relieving endorphins.

In a practical sense, the main difference is that aspirin and ibuprofen work to stop the chemicals (prostaglandins) that cause inflammation – redness, swelling and tenderness. Paracetamol and codeine, on the other hand, are mainly pain-reliever and don’t reduce inflammation.

Of course, if you have any medical concerns then please consult a doctor but For any scientific questions or intriguing queries, please send them in to Ask a Guru, every Friday!

Answer by James Crewdson

Question from Julie via Facebook

*There are some theories that say paracetamol works on a COX-3 protein, which may be a variant of this protein only found in your brain and spine. However, the current most accepted theory is that paracetamol does act on COX-2 and it’s the high levels of peroxide at sites of injury that mean that paracetamol doesn’t work at the site of the injury.

Article by Stuart Farrimond

March 11, 2014

Doctor Stu is editor of Guru Magazine. He originally trained as a medical doctor before deciding to branch out into lecturing, writing, editing and science communication. He drinks far too much coffee, eats lots of ice cream and has a bizarre love of keeping fit.
You can check out Doctor Stu’s blog at or his poncy personal website Here's his .

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