The History of Painkillers: How We Learnt to Kill Pain

For most of human history, pain came with a fairly limited menu of responses. You could grit your teeth, pray, drink something alcoholic, chew a plant, or ask somebody with confidence and questionable qualifications to apply something unpleasant to the affected area. Pain relief existed, but precision certainly did not.

Among the oldest serious painkillers sat the opium poppy. Humans have used opium for thousands of years, and ancient societies understood perfectly well that it could dull pain, induce sleep and produce euphoria. What they did not understand was dosage, chemistry or addiction in anything resembling the modern sense. One batch might soothe you. Another might send you into a sleep from which waking became rather negotiable.

Willow offered another route. Various cultures used willow bark and related plants to treat pain and fever. This fact often produces the tidy historical claim that “the ancient Egyptians invented aspirin”. They did not. Willow contains salicylate-related compounds, while aspirin is acetylsalicylic acid, a chemically modified substance created much later. Still, the botanical connection remains real, which makes aspirin one of those modern drugs with roots stretching surprisingly far into traditional medicine.

The real revolution began when chemists stopped treating medicinal plants as mysterious packages and started separating their components. In the early nineteenth century, the young German pharmacist Friedrich Sertürner isolated morphine from opium. He named it after Morpheus, the Greek god of dreams, which sounds poetic until one remembers what morphine can do in excessive doses. His work produced something fundamentally new: a purified plant-derived drug whose amount doctors could measure far more accurately than a spoonful of variable-strength opium.

Morphine transformed medicine, especially after the hypodermic needle and syringe made injections practical during the nineteenth century. Surgeons and doctors could now deliver powerful pain relief rapidly and predictably. Unfortunately, chemistry had solved one problem while sharpening another. Morphine caused dependence and addiction, and easier administration made both therapeutic use and misuse easier. The history of painkillers starts developing a familiar rhythm here: wonderful medicine, enormous enthusiasm, unpleasant surprise.

Then came one of pharmaceutical history’s stranger episodes. Chemists produced diacetylmorphine, better known as heroin. Bayer began marketing it in 1898 as a cough suppressant and promoted it as a supposedly safer, non-addictive alternative to morphine. The name itself apparently drew on the German word heroisch, suggesting something strong or heroic. It soon became clear that the new wonder drug had rather badly failed the “non-addictive” part of the proposition.

At almost exactly the same moment, Bayer helped bring another drug into the world: aspirin. Felix Hoffmann prepared acetylsalicylic acid in 1897, and Bayer marketed Aspirin from 1899. For decades, the charming corporate story claimed Hoffmann developed it because his father suffered from rheumatism and could not tolerate existing salicylate medicines. It has all the ingredients of a perfect pharmaceutical legend: devoted son, suffering father, brilliant experiment, happy ending. History, inconveniently, may have been messier.

Arthur Eichengrün, another Bayer chemist, later claimed that he had directed the work and pushed aspirin towards clinical testing. Historian Walter Sneader subsequently argued that surviving evidence supported much of Eichengrün’s account. Bayer has disputed parts of that interpretation, so the precise allocation of credit remains controversial. What is certain is that aspirin became one of the most influential medicines ever produced, relieving pain and fever while also reducing inflammation.

Aspirin also changed expectations. People increasingly came to believe that ordinary pain should have a chemical answer. Headache? Tablet. Toothache? Tablet. Sore joints? Another tablet. This cultural shift matters almost as much as the chemistry because twentieth-century medicine gradually transformed pain from something people often endured into something they expected doctors and pharmacists to treat.

Paracetamol followed a more meandering route. Chemists first synthesised the compound in the nineteenth century, but medicine largely overlooked it while related drugs such as phenacetin became popular. Researchers later established that paracetamol was responsible for much of phenacetin’s therapeutic effect, and paracetamol emerged commercially as a major painkiller during the 1950s. By the early 1980s, it had overtaken aspirin as the most widely used over-the-counter analgesic in Britain.

Its reputation became almost domestic. Paracetamol sat in bathroom cabinets, handbags and kitchen drawers, apparently the polite member of the painkiller family. Yet familiarity can disguise risk. Excessive doses can cause severe liver damage, and modern reviews have questioned some of the assumptions surrounding its effectiveness for certain chronic pain conditions. The story does not make paracetamol useless; rather, it illustrates how medicines can become culturally “safe” in our minds long before science has finished arguing about them.

Britain contributed another household name when Stewart Adams and John Nicholson, working at Boots in Nottingham, searched for a better treatment for rheumatoid arthritis. Their research eventually produced ibuprofen. They filed a patent in 1961, Boots launched prescription ibuprofen as Brufen in Britain in 1969, and it later became available without prescription. The researchers had searched for an anti-inflammatory drug that patients could tolerate better than many existing alternatives.

One much-loved story says Adams once tested ibuprofen on his own hangover before giving an important speech. He later confirmed that he had taken the drug himself during development, a reminder that pharmaceutical research in the mid-twentieth century sometimes operated with a degree of personal experimentation that would give a modern ethics committee palpitations.

Meanwhile, scientists learnt much more about how pain actually works. Researchers discovered opioid receptors, inflammatory pathways and signalling chemicals such as prostaglandins. Pain stopped looking like one single phenomenon. Inflammatory pain, nerve pain, post-operative pain, cancer pain and chronic pain could behave very differently. Consequently, the search for one universal painkiller increasingly gave way to combinations and specialised treatments.

Yet opioids never disappeared because few alternatives match their effectiveness for severe acute pain and some forms of cancer pain. That effectiveness helped create another crisis. From the 1990s, prescription opioid use expanded sharply in the United States. Overdose deaths involving prescription opioids rose, followed later by waves involving heroin and then illicitly manufactured fentanyl. Between 1999 and 2023, roughly 806,000 people in the United States died from opioid overdoses involving prescription or illegal opioids.

That grim figure creates one of medicine’s central paradoxes. Opioids remain indispensable drugs, yet the same biological mechanism that makes them powerful painkillers also creates serious risks of dependence, respiratory depression and overdose. The lesson cannot simply be “opioids bad”, because someone recovering from major surgery might reasonably disagree. The harder lesson concerns balance, prescribing, monitoring and the temptation to believe that powerful medicines can ever become completely consequence-free.

Today, pain medicine increasingly combines drugs with physiotherapy, surgery, psychological approaches, nerve blocks, exercise and treatments aimed at specific causes. Researchers continue searching for effective analgesics without the disadvantages that accompanied previous generations. The dream sounds familiar: morphine without addiction, aspirin without stomach problems, paracetamol without liver toxicity, strong relief without dependence.

Humanity has therefore spent thousands of years trying to silence one of the body’s oldest alarm systems. We have become remarkably good at doing so, although every generation seems to rediscover the same inconvenient principle. Painkillers rarely remove pain for free. Somewhere between the opium poppy and the modern pharmacy shelf lies a history not simply of medical progress, but of our repeated belief that this time, surely, we have finally invented the perfect tablet.