Pain has been the target of medications for centuries, yet it remains difficult to treat.

For centuries, opium was the only powerful painkiller available, and probably the most important drug in a doctor's bag. The ancient Egyptians used opium, extracted from the poppy (Papaver somniferum), to stop children crying, and the ancient Greeks prescribed it enthusiastically as a health tonic though it was known to be addictive even then.

Benedictine monks in 800 CE used it as a painkiller and an anaesthetic. Not surprisingly, opium has been called the 'joy plant' and 'a gift from God'. Florence Nightingale, who was an invalid much of her life, found pain relief by injecting opium.

Morphine, the active ingredient, was extracted in 1806 and later marketed by Merck. Even today, opioids (morphine-like chemicals) are the mainstay of severe pain management in the terminally ill.

Opioids act on receptors on the nerve cells that process painful stimuli. They prevent nerve cells from releasing neurotransmitters, the chemicals that pass a nerve impulse from cell to cell.

From aspirin to Vioxx

Aspirin is today's most popular drug. But this blockbuster medication has been around for thousands of years. In the 5th century BCE, the Greek physician Hippocrates wrote about a bitter powder extracted from willow bark that had the ability to ease aches, pains and fevers. In 1828, pharmacists isolated the active compound from the willow tree - salicin - and it became a popular treatment for rheumatic pain. In 1899 the German pharmaceutical company Bayer modified salicin to produce the less toxic acetylsalicylic acid, coining the trade name Aspirin.

Aspirin is an example of a non-steroidal anti-inflammatory drug (NSAID). As well as being a painkiller, it reduces fever and inflammation. Another common NSAID is ibuprofen. Both are sold over the counter (though aspirin often causes side-effects). Others are available on prescription.

NSAIDs act on a group of enzymes known as cyclooxygenases (COX), which are needed to make a range of signalling molecules. One drawback is their tendency to damage the lining of the gut. When it was discovered that the COX enzyme in the gut lining differed from that responsible for pain and inflammation, researchers rushed to develop inhibitors that did not affect the gut enzyme. These new blockbuster drugs, the COX-2 inhibitors, were widely used until doubts were raised about their safety.

Coal tar and cannabis

In the early 19th century, English industrial chemists produced a novel painkiller - phenacetin - from coal tar. This eventually led to paracetamol, a useful treatment for chronic pain because it can be used with other analgesics, including opioids, in low doses. It must be used with caution as high doses can damage the liver.

Cannabis (an extract from Cannabis sativa) can be a powerful painkiller. The Romans used it to ease pain and it is mentioned in the Jewish Talmud. Even Queen Victoria, in the 19th century, took cannabis to ease period pains.

Cannabis is a prohibited substance in many countries, including the UK, so people who use it medicinally are breaking the law. People with multiple sclerosis say smoking cannabis reduces spasms, pain and tremors. Clinical trials to test the medical effects of cannabis's main active ingredient - delta-9-tetrahydrocannabinol (THC) - are ongoing.

Pharmaceutical companies have produced THC capsules and have started developing THC aerosols and inhalers that don't harm the lungs. The results are encouraging, though some people with multiple sclerosis say that the medicinal form does not provide the same pain relief as smoking cannabis. Growing evidence that cannabis consumption increases the risk of psychosis is likely to limit its use, however.

Despite these substances, pain - particularly chronic pain - is common and difficult to treat. The hunt for compounds that lessen pain continues.