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How does Tylenol -- or acetaminophen -- make my headache go away?

"Acetaminophen is an analgesic and works, for example, against headaches, muscle pain, knee pain, and toothaches," says Carol T. Walsh, associate professor of pharmacology at the School of Medicine. "When you talk about headache, though, it gets a bit more complicated, because there are different types of headaches. There are cluster headaches, migraines, and others. The therapy there is more complicated. Acetaminophen, for instance, is not the drug of choice for a migraine.

"Acetaminophen is like aspirin in that it inhibits an enzyme known as cyclooxygenase, or cox. Cox inhibition prevents synthesis of certain prostaglandins [physiologically active substances with diverse hormone-like effects], which augment the pain-inducing effects of certain chemicals released on tissue injury or in response to various kinds of stimuli. When these chemicals are released, they stimulate the sensory nerve endings, and that's ultimately translated in the brain as a sensation of pain. Prostaglandins augment the ability of those chemicals to activate peripheral receptors [meaning that the pain sensation is felt keenly]. If you take prostaglandins and inject them into tissue, you can actually induce pain where there was none before.

"Here's the exciting and problematic part of this: acetaminophen is pharmacologically classified with all the drugs that are like aspirin. But it has two major differences: it does not suppress symptoms of inflammation and it does not produce side effects such as ulcers, which are attributed to cox inhibition. So it stands apart from all these other drugs." And it turns out that acetaminophen inhibits prostaglandin synthesis weakly.

So how exactly does it work? "It's the question that any smart medical student asks me when I give my lectures," Walsh says. "And it always kills me because I don't have the answer yet. An experiment published several years ago suggests that there might be a component of the effect of acetaminophen that could be explained by an effect on the central nervous system that's similar in some ways to the way the opioids work as analgesics." Opioids possess some properties or characteristics of opiate narcotics but are not derived from opium.

"Ask the Bridge" welcomes readers' questions. E-mail bridge@bu.edu or write to "Ask the Bridge," 10 Lenox Street, Brookline, MA 02446.

21 September 2001
Boston University
Office of University Relations