How Does a Painkiller Know Where It Hurts?

A painkiller does not know where it hurts. It goes everywhere and interrupts one step in a long chain. That is why each one has a cost somewhere else in the body.

This is an explanation, not advice. Follow the label, and ask a pharmacist or doctor about your own medicines.

Everyday painkillers

Paracetamol

Nobody can tell you exactly how it works. It is not an anti-inflammatory. The best current answer is that it acts in the brain and spinal cord and turns the volume down on the message.

The gap between a normal dose and a dose that damages the liver is small. It is a leading cause of acute liver failure, and there is no pain at first.

Ibuprofen

Damaged tissue releases chemicals called prostaglandins, which cause swelling and make nerve endings more sensitive. Ibuprofen blocks the enzyme that makes them.

The same enzyme maintains the mucus that protects your stomach. That is where stomach bleeding comes from. It also puts strain on the kidneys, especially if you are dehydrated.

Aspirin

People chewed willow bark for fever and aching joints for thousands of years. Aspirin blocks the same enzyme as ibuprofen, but permanently for the life of the cell.

Platelets, the cells that form clots, cannot replace the enzyme. That is the basis of low-dose aspirin. It is also why aspirin is kept away from children with a fever.

Naproxen and diclofenac

Naproxen works like ibuprofen and lasts longer, so it has longer to affect the stomach. Diclofenac is strong against inflammation and harder on the heart. As a gel, most of it stays where you put it.

Capsaicin cream

Capsaicin is what makes chilli hot. On the skin it makes nerve endings fire until they run out of the chemical they need to send signals. Nothing is healed. The messenger is exhausted.

Opioids

Codeine

Codeine does almost nothing by itself. The liver has to convert it into morphine, and that conversion varies from person to person. About one person in ten converts almost none. A smaller group converts it far too fast.

Tramadol

It is a weak opioid that also raises serotonin and noradrenaline, the chemicals antidepressants act on. So it interacts with many medicines and can trigger seizures.

Combination tablets

Tablets with two names on the box are usually paracetamol with an opioid. The logic is sound.

The trap is that people take the combination tablet and then take plain paracetamol as well. That is a double dose. It is one of the most common accidental overdoses, and it happens to careful people.

Morphine, oxycodone and fentanyl

Your body makes its own opioids. Morphine floods the same receptors. It does not so much stop the pain as stop you caring that it is there.

A slow-release form of oxycodone was sold as less addictive. That claim did not hold up, and it played a part in the opioid crisis.

Fentanyl is roughly 100 times stronger than morphine. In hospital that is useful. In street drugs it is lethal, because the difference between a dose and a fatal dose is too small to see.

Tolerance

The nervous system adjusts to opioids, so the same dose does less. In some people, long-term use makes the nervous system more sensitive to pain.

Other approaches

• Ketamine blocks a receptor that winds pain up. At low doses it is useful in emergency medicine.
• Nitrous oxide wears off in minutes, which is why it is used in childbirth and dentistry. Heavy repeated use inactivates vitamin B12 and damages nerves.
• Lidocaine stops the message being sent. It holds shut the tiny gates a nerve needs in order to fire, locally and temporarily.
• Steroid injections shut down inflammation. Relief can last months, but repeated injections weaken the tissue.
• Nerve pain medicines, such as gabapentin, pregabalin and amitriptyline, calm nerves that fire when nothing is wrong. They help with shingles, sciatica and diabetic nerve pain. They do nothing for a sprained ankle.
• Triptans narrow the widened blood vessels of a migraine. They do nothing for an ordinary headache.

The placebo

A tablet with nothing active in it reduces pain in many people. When researchers blocked opioid receptors with naloxone, the relief disappeared.

So the relief was real. The brain made its own opioids. Expectation is a drug delivery system.

The short answer

No painkiller simply removes pain. We have so many because pain is not one thing. A broken bone, a migraine, a burn and a misfiring nerve are four different problems.

Reaching for the same box for all four is why many people decide that painkillers do not work.