Have you ever had a headache? Chances are you have; almost all of us do once in a while. And chances are you took some kind of medicine to ease your headache. That medicine was most likely a relative of aspirin.

You may also have taken aspirin or its relatives for other problems, like inflammation (swelling of joints or other parts of the body) or fever. But did you know that about 80 billion aspirin tablets are taken per year for these problems, as well as many others? For example, millions of people take aspirin to help prevent heart attacks! There are good reasons a doctor might say, "Take two aspirin and call me in the morning"!

In this article, Dr. Luke Hoffman leads an exploration of aspirin. You will learn about the many benefits of aspirin, as well as some good reasons NOT to take this medication! You will also come to understand why Bayer has called aspirin "the wonder drug that works wonders!"

Aspirin is a member of a family of chemicals called salicylates (see below for chemistry and structure). These chemicals have been known to people interested in medicine for centuries.

One of the first and most influential physicians, Hippocrates, wrote about a bitter powder extracted from willow bark that could ease aches and pains and reduce fevers as long ago as the fifth century B.C. In the 1700s, the scientist Reverend Edmund Stone wrote about the success of the bark and the willow in the cure of the "agues," or fevers with aches. With a bit of chemical detective work, scientists found out that the part of willow bark that was (1) bitter and (2) good for fever and pain is a chemical known as salicin.

This chemical can be converted (changed) by the body after it is eaten to another chemical, salicylic acid. It was a pharmacist known as Leroux who showed in 1829 that salicin is this active willow ingredient, and for many years it, salicylic acid (made from salicin for the first time by Italian chemist Piria), and close relatives were used at high doses to treat pain and swelling in diseases like arthritis and to treat fever in illnesses like influenza (flu).

 

Salicylic acid

The problem with these chemicals was that they upset the user's stomach fairly badly. In fact, some people had bleeding in their digestive tracts from the high doses of these chemicals needed to control pain and swelling. One of these people was a German man named Hoffmann. His arthritis was pretty bad, but he just couldn't "stomach" his salicylic acid. Enter this man's son, German chemist Felix Hoffmann, who worked for a chemical company known as Friedrich Bayer & Co. Felix wanted to find a chemical that wouldn't be so hard on his dad's stomach lining; reasoning that salicylic acid may be irritating because it is an acid, he put the compound through a couple of chemical reactions that covered up one of the acidic parts with an acetyl group, converting it to acetylsalicylic acid (ASA). He found that ASA not only could reduce fever and relieve pain and swelling, but he believed it was better for the stomach and worked even better than salicylic acid.

 

Acetylsalicylic acid

Unfortunately, Hoffmann had to wait for fame. He finished his initial studies in 1897, and his employers didn't pay much attention to it because it was new and they were cautious -- they didn't think it had been tested enough. By 1899, though, one of Bayer's top chemists, a scientist named Dreser, had finished demonstrating the usefulness of the potent new medicine and even gave it a new name: aspirin. It is believed that the name comes from a plant relative of a rose that makes salicylic acid (several plants make this compound, not just the willow). The Bayer company could then support the tested medicine; they spread the word and marketed the new pill widely.

Over the next hundred years, this medicine would fall in and out of favor, at least two new families of medicines would be derived from it, and innumerable research articles would be published about aspirin. Thousands have been published in the past five years alone! One of the most important pieces of research about aspirin came in the early 1970s, when a British scientist named John Vane and his colleagues showed how aspirin works (see the following sections). His work was so important that he and his colleagues were awarded the Nobel Prize in Medicine in 1982. Dr. Vane was even made a British knight for his work!

No one completely understands how pain works. Actually, a lot is known about pain, but the more we find out the more questions arise. So let's take a simplified view.

Pain is really something you feel in your brain. For example, let's say you hit your finger with a hammer (please don't try this at home). The part of your finger that is damaged has nerve endings in it -- these are little detectors in your joints and your skin that feel things like heat, vibration, light touch from things like the mouse you're holding, and, of course, big crushing shocks like being hit with a hammer. There are different receptors for each of these types of sensations. The damaged tissue in your finger also releases some chemicals that make those nerve endings register the crushing shock even stronger -- like turning up the volume on your stereo so you can hear it better. Some of these chemicals are prostaglandins, and working cells in the damaged tissues make these chemicals using an enzyme called cyclooxygenase 2 (COX-2).

Because of the prostaglandins, the nerve endings that are involved now send a strong signal through nerves in your hand, then through your arm, up your neck and into your brain, where your mind decides this signal means, "HEY! PAIN!" The prostaglandins seem to contribute just a portion of the total signal that means pain, but this portion is an important one. In addition, prostaglandins not only help you to feel the pain of the damaged finger, but they also cause the finger to swell up (this is called inflammation) to bathe the tissues in fluid from your blood that will protect it and help it to heal. Remember this is a simplified version of the pain story; lots of chemicals seem to be involved in this process, not just prostaglandins.

This pathway works very well as far as telling you your finger is hurt. The pain serves a purpose here: It reminds you that your finger is damaged and that you need to be careful with it and not use it until it's healed. The problem is that, sometimes, things hurt without the hammer or for any other good reason. For example, sometimes you get a headache, probably because your scalp and neck muscles are contracted from stress or because a blood vessel in your brain has a spasm. Many people have arthritis, which is swelling and pain in the joints such as the knuckles or knees, and this problem can not only make people uncomfortable, it can damage the joints permanently. And many women have pain in their abdomens during their periods, usually known as cramps, for no known useful reason. These processes appear to involve prostaglandins as well.