Tylenol has been used to treat common pains and fevers since 1893. Why is it still among the most commonly taken painkillers?Credit: Valerie Macon/AFP via Getty
Tylenol — also known as paracetamol, or acetaminophen — has been a common household medicine for decades, but has rarely received as much attention as this week when Donald Trump linked it to autism.
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The claim was swiftly discredited by several researchers, who pointed out that the most robust and largest studies testing the possible impact of pregnant women taking the drug find no evidence of any connection to autism in children. Outside the United States, paracetamol is still recommended as a first-line treatment for pain and fever in pregnancy, and scientists say there have been no causal associations between the drug and neurodevelopmental disorders. Untreated pain and fever, on the other hand, can harm mothers and fetuses1.
Paracetamol is one of the safest medicines available, with very few possible complications “as long as you stick to the [recommended] doses”, says Tony Dickenson, a neuroscientist at University College London. The drug is far more lethal in animals with different liver enzymes — such as snakes. That’s why in 2013 the United States airdropped thousands of paracetamol-laden dead mice to control invasive populations of brown tree snakes on the Pacific Island of Guam. Here’s what we do and don’t know about the drug.
Mysterious mechanism
Despite decades of clinical use, and the proposal of several molecular mechanisms, researchers still don’t fully know how paracetamol dulls pain.
Most research on paracetamol has been directed to what happens inside the brain, says Dickenson. “Paracetamol, apart from being an analgesic, is pretty good at reducing fevers,” he says. That’s controlled by the brain’s hypothalamus. “So, the drug is clearly getting into the brain.”
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This action on the central nervous system — protected behind the blood–brain barrier — makes paracetamol different to other, anti-inflammatory painkillers such as ibuprofen and aspirin, which tend to work at the peripheral site of tissue damage. Studies also suggest the drug acts on neuronal pathways between the brain and the spinal cord that alter the gain of pain signalling2. “There are multiple systems and all of those are critical for pain processing,” says Dickenson. “So, it is pretty difficult to tease out what’s going on.”
New evidence suggests that the drug can also act on neurons in the body that detect harmful stimuli — called nociceptors — in a similar way to a local anaesthetic3.
“We were very surprised,” says study co-author Avi Priel, a pain pharmacologist at the Hebrew University of Jerusalem. “We showed that it had some peripheral effect directly on the pain system.” Still, the findings cannot explain the drug’s effect on temperature, so it’s possible that pain and fever relief are controlled by different systems, he adds.
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