Illustration: Lee Wolf

Ask The Professor

How does acetaminophen relieve pain? I’m always amazed that it can take my headache away—and reduce a fever—so quickly.

This month’s faculty expert, Ewan McNicol, assistant professor of anesthesiology, responds:

The short answer to this question is that we don’t fully understand how acetaminophen works. Commonly known by its brand name of Tylenol, acetaminophen belongs to a class of painkillers known as non-opioid analgesics. This class of drugs also includes aspirin, traditional non-steroidal anti-inflammatories such as ibuprofen and naproxen, and the newer COX-2 inhibitors like celecoxib—popularly known as Celebrex.

Non-opioid analgesics work by inhibiting an enzyme known as cyclooxygenase (COX). COX is a catalyst for the conversion of a fatty acid contained in cell walls—arachidonic acid—to substances known as prostaglandins.

Prostaglandins serve a number of protective functions in the body, but they can also produce pain, inflammation and fever. They cause pain and inflammation after cell injury by a number of mechanisms, primarily at the site of the injury in the peripheral nervous system, that is, nerves outside the brain and spinal cord, but also in the central nervous system. They elevate body temperature by affecting the heat regulating center of a region of the brain known as the hypothalamus.

By blocking COX and, therefore, the subsequent production of prostaglandins in the central and peripheral nervous systems, non-opioid analgesics reduce both fever and inflammation. Acetaminophen, however, differs from the other non-opioids in that it does not block COX in the peripheral nervous system to an appreciable extent. It appears to reduce pain primarily in the central nervous system by more than one mechanism, possibly in part by inhibiting a form of COX known as COX-3, although this is the subject of much debate.

It is, therefore, considered to be a weak analgesic and does not possess anti-inflammatory properties. What this means to you is that acetaminophen is great for headaches, fever and minor aches and pains, but won’t reduce inflammation due to, say, a muscle sprain.

Do you have a question for “Ask the Professor”? Email it to taylor.mcneil@tufts.edu.