Pain Relief - Treatment & Needs

A brief history of pain relief

People have always searched for ways to relieve pain. In 6000 B.C., the ancient Sumerians were cultivating opium poppies and using them as analgesics. Morphine, the active pain-killing agent in poppies, was isolated in the early 1800s. We now know morphine works by tapping into a part of our own pain response system that normally damps down pain, so that we can continue to function. Without our natural versions of opium, called opioids, common painful situations such as childbirth or torn ligaments would be too intense. Through an understanding of how natural opioids work, medicinal chemists have made many opiates that are now widely used for the control of severe and chronic pain.

Another ancient mainstay of pain relief is a substance first discovered in willow trees. Around 400 B.C., the Greek physician Hippocrates prescribed willow leaves and bark for treatment of pain and fever. At the end of the 19th century, a German chemist converted the active agent in willow bark into acetylsalicylic acid and aspirin was born, still the most widely used human analgesic.

At first no-one knew how aspirin reduced pain, inflammation and fever. Then, in the early 1970s, the British scientist Sir John Vane, working in organs and tissues isolated from animals, discovered that aspirin and similar drugs inhibit the production of prostaglandins, chemical messengers produced in inflamed tissues that make us more sensitive to pain. Sir John shared the 1982 Nobel Prize for his discoveries on the mechanism of action of aspirin.

We now know much more about aspirin's targets - the cyclooxygenases or COX enzymes. Many new non-steroidal anti inflammatory drugs (NSAIDs) have been developed, including a class called the COX-2 inhibitors. These "coxibs" are very important in the control of chronic pain such as arthritic pain, but cause less stomach irritation than aspirin and other first-generation NSAIDs such as ibuprofen.

Any medicine powerful enough to help, also has power to harm. Clinical studies generally only involve several hundred patients, so adverse effects are sometimes not seen until thousands and thousands of people have used a new medicine. We now know, for example, that coxibs increase the risk of heart problems in people with a pre-existing condition.

21st century pain relief

Present day pain relief has its limitations. The ideal analgesic should reduce pain levels rapidly and for many hours so that normal life can resume, but not dull pain so much that people unknowingly damage themselves. In addition, it should not cause physical dependency or unacceptable side-effects such as vomiting and drowsiness. Current NSAIDs and opioids fulfil some of these criteria but not all.

Moreover, because pain is not a well-defined physical entity many people are poorly served by the currently available analgesics. Different people feel different amounts of pain depending on their previous experience of pain, their social circumstances, even their gender. Women for example are thought to be more sensitive than men to pain. Luckily, many new pain killers are becoming available.

The most widely used analgesic for treating intense pain is morphine, but one big drawback to opiate drugs is that they are tremendously addictive. Replacements for these drugs have been long awaited and a compound inspired by the natural world may be the answer. Skin secretions from the Ecuadorian tree frog include Epibatidine, which is 200 times as effective as morphine. Epibatidine stops some messages passing between nerve cells, which blocks pain. But it also causes paralysis by blocking message transmission between nerves and muscles, so Epibatidine will never be an analgesic itself. However, chemists have recently made an epibatidine-related molecule called ABT-594 that leaves the muscles alone and does not appear to be addictive. It is currently in clinical trials.

The biggest challenge for physicians is treatment of chronic and neuropathic pain, which is often generated by our body sending out false alarms. Examples of neuropathic pain include: pain that persists after shingles lesions have cleared; pain due to widespread nerve damage, most commonly caused by diabetes or chronic alcohol use; and components of cancer pain. Here, the natural world is once again helping out. The Conus snail produces a cocktail of chemicals to paralyse and kill its prey. Understanding how these predatory sea snails' venom acts at a molecular level led to the identification of a component that specifically blocks the pain process. A synthetic version, ziconotide, is in the late stages of clinical development.

In the early 1990s researchers testing a new anti-epileptic called gabapentin in animals found it reduced pain and so clinical trials in neuropathic pain conditions were started. Gabapentin was approved in March 2000 in the UK for the treatment of neuropathic pain, although it is not known exactly how it accomplishes this action.

In addition to medication, psychological techniques such as relaxation training, stress management and education, can be extremely helpful in helping people deal with pain. Other non pharmaceutical approaches include TENS (transcutaneous electrical nerve stimulation) and acupuncture. Experiments in animals suggest that, at least in part, acupuncture works by stimulating the release of opioids. There is also a version of acupuncture that uses electricity: electro-acupuncture.

The use of electricity for the relief of pain goes back many thousands of years - the ancient Egyptians used electric fish. By the mid-1800s, physicians and dentists were beginning to use electrical stimulation as an analgesic. More recently, TENS has been tested in animal models of acute, inflammatory and neuropathic pain. Some clinical trials have provided evidence for its efficacy in people. However, it is still not clear how the TENS machine, which delivers rapid electrical pulses to the skin, reduces pain.

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