Where Pain Medicine Comes From

The unusual history of whiskey surgery and cocaine tooth drops

There once was a time without pain killer. We had no aspirin, no ibuprofen, no anesthetic for surgery. How did we manage pain in the past? What led to the first breakthroughs in pain management? Can it help us confront chronic pain today?

It can be difficult to imagine a life without pain medicine. Just this morning, I awoke with a pressure headache due to an incoming storm front. I took a few ibuprofen and went on with my day. Most of us have passing pains like these: a stiff back from garden work, sore muscles from an overzealous romp with kids or grandkids, minor headaches. Then there are more cyclical issues—injury, migraines, PMS, and chronic conditions that can only be managed with some form of pain relief. Now imagine a life without that possibility.

In 1810, novelist Francis (Fanny) Burney was diagnosed with breast cancer. She survived, thanks to the intervention of Napoleon’s surgeon in 1811. He performed a mastectomy without anesthetic (because anesthetic had not yet been invented).

We don’t normally think of anesthetic and bathroom cupboard pain pills as related, but in fact breakthroughs in pain relief were largely driven by the need to perform surgery on patients who were awake and feeling.

Yet — when the dreadful steel was plunged into the breast — cutting through veins — arteries — flesh — nerves — […] I began a scream that lasted unintermittingly during the whole time of the incision […] — letter by Fanny Burney, 1812

Weird remedies

There were various remedies for pain; whether or not they effected a cure was another matter. Leeches, for instance, were popular from Ancient Egypt to 18th-century Europe. Another curious method was tobacco smoke enema… to literally ‘blow smoke’ up your nether region (still in use in England in the 1800s!)

Medieval recipes could be even more curious, with mixtures of “Take equal amounts of radish, bishopwort, garlic, wormwood, helenium, cropleek and hollowleek.” Some of the items infused might have beneficial properties (both garlic and wormwood were good at killing parasites), but the indigenous Americans had better luck with willow bark (it contains salici, from which comes salicylic acid, also in aspirin). And of course, there was whiskey and brandy — strong drink was often administered before the worst of surgery not only to dull pain but to “steel” the nerves.

Despite these concoctions, real pain relief did not come to the West until the arrival of the opium poppy and its resin. Opium had been used in the Middle East and by Ancient Greeks for many thousands of years, but came to Europe largely by way of China and India. From 1637 to the 1700s, opium was, in fact, the main commodity of British trade with China. Expensive to produce and unpredictable (due to ineffective means of measuring dose, among other problems), opium was usually mixed with alcohol to make laudanum. It worked — sort of. It at least kept crying babies quiet — sometimes indefinitely, since overdose meant certain death.

Breakthroughs in pain relief

The first real achievements in pain relief occurred during 1804–1805 in the small, private lab of a man named Freidrich Wilhelm Adam Serturner. A German chemist and pharmacist, he set about testing a variety of plant compounds in an attempt to isolate the element necessary to effect pain relief. That meant trial and error. It also meant Serturner poisoned himself and three assistants, and only survived by forcing everyone to take a vinegar emetic (to make them vomit).

His discovery? A fine white powder, an alkaloid. Alkaloids come from plants and contain at least one nitrogen atom — so “alkaline.” As a result, the -ine was put at the end of all such compounds, including caffeine and nicotine. But the substance Serturner purified (with the power to knock out its unsuspecting victims) was very powerful indeed. He named it after the Greek god Morpheus: morphine.

So, why does it work?

Why do we feel pain?

The fact that we feel pain is related, in part, to how and why we feel anything at all: that is, our sense of touch. It begins as signals in the skin, as sensory receptors send messages via our nerve fibers (a-delta fibers and c fibers) to the spinal cord. From there, it travels to the brainstem, then into the brain where sensation is registered and processed. Pain (stubbing your toe in the dark, let’s say) is a warning. It tells you something has just gone wrong, and “just gone wrong” pain is “acute” pain — immediate, in the now.

The brain has to decide what to do next after an acute pain incident. How bad is it? Once processed, a lot of other things might happen: swelling as the body responds to injury, increased heart rate, rushing blood, even the release of adrenaline. “Chronic” pain, on the other hand, is sustained and continued over long periods of time. Here is often where something has gone wrong with the system; a disease like arthritis keeps the pain signals kicking over, or an autoimmune response might keep pain going after the injury or illness is long gone.

In either case, what we have is a “pain pathway,” input going to the brain, and the brain receiving and perceiving pain in the message, and then re-sending messages the other way. But not everyone feels pain the same way. Two people with the same injury can have very different experiences, because it depends on exactly what the brain decides to do with that pathway of information.

Let’s assume you and a friend both injure your knee. The brain can release endorphins, which act like pain suppression. But perhaps your friend’s brain sends many more endorphins than yours. Or, perhaps the pathway of pain information runs differently for you, because of other internal or external factors. He gets up and moving right away, because he doesn’t “feel” the pain as you do.

Since the brain can naturally shut down or dampen pain (and there have been miracle stories of people who climbed, jumped, or ran with broken bones), that means interrupting pain messages is possible. It’s called the “endogenous analgesic system,” and it prevents excess pain from interfering with the normal body functions. Opioids, like morphine, attach to proteins called opioid receptors and block the signals from getting to the brain in the first place. That’s also how codeine, and even cocaine work (and if you were surprised we once gave babies laudanum, wait till you hear about “soothing coco drops” for teething children).

Pain relief in surgery ultimately comes by way of “sweet oil of vitriol” (a knock-out drug from ethanol and sulfuric acid), but the next steps toward pain relief in general don’t come from medicine at all. It comes from a fashion fad for quick setting, long-lasting dye… and a whole lot of industrial waste in the form of coal tar.

In 1897, German chemist Felix Hoffman began synthesizing salicylic acid, pulling the building block compounds from the sludge of factory waste. You wouldn’t need willow bark anymore, you could build the compounds synthetically. You could also modify them. Hoffman made acetylsalicylic acid at his dye company. They patented it as “aspirin,” and began selling 40 million tablets a year. It did so well, the company — Bayer — stopped making dyes and produced synthetic drugs.

There are, then, three types of primary pain relief strategies: 1) Aspirin: stops pain at the source, locally blocking it in the body. 2) Anti-inflammatories, like ibuprofen, stop the body’s chemical responses. 3) Morphine and other opioids block pain in the brain. Today’s researchers have begun to investigate other alternatives — like very specific targeting of proteins that carry pain messages, or even nanotech to interact with electrical signals in the body and other “technaceuticals.”

The future of pain relief?

Today, quite a lot is being said about the use of Cannabis and CBD to treat a variety of conditions. Additionally, however, scientists have been working toward solutions that don’t require chemicals. High-frequency spine stimulation has been used recently for neuropathic pain; other techniques involve biofeedback, meditation, even gene therapy and hypnosis.

For those of us in a modern, Western context, we are raised to think of pain as something that can be relieved, fixed, healed, altered. If our forefathers and mothers seemed more stoic than we do (Frances Burney described the scrape of the knife on her breast bone to her sister, in peculiar matter-of-fact), it’s only because there were no other options, and our expectations about pain change the way we experience it. It might be a useful indicator of injury, and it’s our body’s means of defending up from worse harm. It would be dangerous not to have any pain at all, no early warning sign of trouble, no indicators that we were unwell. But for all that, I am very thankful for the aspirin in the cabinet.

Author/Editor. Writing about history, science, & medicine for Scientific American, Undark, Globe and Mail, and more. brandyschillace.com. Twitter:@bschillace

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