- It had been thought that acetaminophen only worked in the brain and spinal cord.
- This breakthrough sheds new light on how AM404 operates and could lead to safe, targeted painkillers.
- Potential overdose and a variety of side effects, including liver damage, make proper dosing critical.
Acetaminophen works differently than previously thought, not only silencing pain signals in the brain, but at its roots within the body.
That’s a new finding on the old painkiller from researchers at Hebrew University in Jerusalem. They found that the drug impacts nerve endings in the body where a pain originates.
The findings are published in the journal PNAS (Proceedings of the National Academy of Sciences USA).
Acetaminophen is known as paracetamol outside the U.S. and Japan. Common brand names are Tylenol® and Panadol®, among others.
The new discovery
According to the study’s background material, acetaminophen’s active metabolite, AM404, “shuts down specific sodium channels in pain-sensing neurons” so that the pain signals don’t even reach the brain. The release said the discovery “not only reshapes our understanding of how one of the world’s most common painkillers works, but also opens the door to developing safer, more targeted pain treatments.”
Scientists for decades believed the drug stopped pain by working in the brain and spinal cord. But the new study proves the drug also works outside the brain in the nerves that detect pain.
When someone takes acetaminophen, the body makes AM404 in the pain-sensing nerve endings. AM404 then turns off sodium channels that help send out pain signals. So the message isn’t even sent.
“This is the first time we’ve shown that AM404 works directly on the nerves outside the brain,” said one of the key researchers on the project, Prof. Alexander Binshtok, who is on the university’s Faculty of Medicine and Center for Brain Sciences.
The research team believes the breakthrough could lead to new types of painkillers, since the metabolite targets the nerves that carry pain. Such a painkiller might avoid the numbness, muscle weakness and other side effects that are common with traditional anesthetics, they said.
About acetaminophen
Acetaminophen is commonly used for mild to moderate pain and to reduce fever.
Drugs.com reports that it’s the most common over-the-counter and prescription medicine and is a mainstay ingredient in many products, from cold medicines to sleep aids and allergy medication. Some 600 products contain acetaminophen, prompting warnings to read the labels and make sure that the recommended overall dose is not exceeded if someone uses more than one product.
Getting too much can lead to liver damage and Medline Plus warns that is “sometimes serious enough to require liver transplantation or cause death.” Because the medicine is found in so many products, care has to be taken. The drug also has side effects, including nausea, vomiting and constipation. Some people develop a rash or hives.
Warnings include making sure the drug doesn’t interact with other medications, as well.
The drug is considered one of the safer painkiller options for pregnant women, at the proper dose.