e’ve been fighting pain almost since the dawn of human existence, with varying degrees of success. Ancient Egyptians fired catfish skulls into ash, boiled the dust in oil, and rubbed what was left on aching heads. In Hippocrates’ time, willow bark tea was advised. Whenever I stubbed my toe as a kid, my grandfather would ask for a hammer so he could bang my thumb. He assured me that would make the toe pain vanish.
Turns out the Hippocratic-era physicians weren’t far off. Salicin, the active ingredient in willow bark, is an organic compound related to synthetic aspirin (acetylsalicylic acid).
In Hippocrates’ time, about 400 BC, no one understood how or why willow bark relieved pain. That hasn’t changed much. We still don’t fully understand how contemporary, over-the-counter pain medicines work. But we’ve come a long way.
Aspirin belongs to the “non-steroidal anti-inflammatory drug” (NSAID) category along with ibuprofen (Advil, Motrin) and naproxen (Aleve). All work in similar ways to limit the body’s inflammatory response, which is what produces pain, swelling, redness, heat, and function loss. When confronted by trauma, bacteria, toxins, heat, or other stimuli, the body’s inflammatory response — a vital part of the immune system — kicks in. Increased blood flow circulates immune cells, and white blood cells called phagocytes are called to the scene to consume dead cells and microbes. Swelling quarantines foreign particles. Pain reminds us something’s wrong and urges us take caution, to rest.
But pain is also uncomfortable. The body’s alarm bells clang. Swelling, redness, and heat get old fast. We want them to stop. NSAIDs help reduce the biochemical reactions that generate the body’s excess inflammatory response and the associated physiological symptoms. NSAIDs block an enzyme called cyclooxygenase (COX). Blocking this enzyme keeps the keeps the body from producing excessive amounts of hormones known as prostaglandins.
Prostaglandins are signaling molecules, which join the inflammatory cascade and make pain receptors more sensitive as well as cause fever. High levels of prostaglandins disturb our temperature regulation system. Prostaglandins and the COX enzymes orchestrating their production are lords of misery.
But COX enzymes also have other functions. Taking an NSAID to reduce the function of COX enzymes has its own set of consequences. The body responds by producing fewer prostaglandins (which protect the lining of the gut) and thromboxanes (which help blood clot properly). That’s why you need to take NSAIDs on a full stomach, and never before or after surgery. They can cause stomach irritation and reduce the body’s clotting abilities.
Acetaminophen (Tylenol, Panadol) is related to the NSAID family. Like aspirin, ibuprofen, and naproxen, acetaminophen blocks the COX enzyme. But it does this only in a limited part of our nervous system rather than throughout the body. Acetaminophen also only blocks one kind of the COX enzyme, while NSAIDs block two. This may explain why acetaminophen works for pain and fever, but not for inflammation, though argument on the subject persists.
Biologically, NSAIDs and acetaminophen work differently. Their clinical applications also vary. Since acetaminophen doesn’t address inflammation while NSAIDs do, the latter are the drug of choice for injuries like sprains. Since NSAIDs cause stomach irritation and affect clotting, acetaminophen is preferred for patients on an empty stomach, ahead of surgery, or for those susceptible to blood clots. Acetaminophen is more toxic in an overdose, but generally less toxic when used long term at recommended dosages, especially for older people. Because of its potential overdose toxicity, people who take acetaminophen in conjunction with other medications must check carefully to avoid doubling up. Many cold medicines contain acetaminophen, for example.
With NSAIDs and acetaminophen available over-the-counter (at least in the United States), people can be lulled into thinking they’re harmless. They’re not. They’re drugs, and as such need to be taken seriously.
Having inexpensive, accessible, and effective medications for pain is a godsend. I’ll take an aspirin over a boiled, ashen catfish skull or my granddad’s hammer any day. Even if I don’t fully understand how the pill works.