Pain discovery may lead to new drug

Drugs that could at last ease the chronic pain in arthritis or after serious injury suffered by millions of people are in prospect as a result of a discovery announced today.

Chilli anaesthetic turns off pain

Despite enormous investments by industry, pain management has changed little during the last decades. Conventional analgesics such as morphine or aspirin do not just alleviate pain but can produce side effects too. And, in cases of chronic pain that lasts for months or even years, conventional drugs can become gradually ineffective.

Today, in the journal Nature, a Swiss team says that it has found a potential target for drugs to block pain transmission without causing typical side-effects of conventional pain killers.
Prof Hanns Ulrich Zeilhofer and colleagues at the University of Zurich identified a target, which is found in a part of the grey matter of the spinal cord, called the dorsal horn, where signals from pain nerves are relayed to the brain.

The protein receives signals from a messenger chemical, called GABA, which is found throughout the nervous system and inhibits signals. In chronic pain sufferers, these signals decline in the dorsal horn and, as a result, the pain continues.

To restore the signals, Prof Zeilhofer and his team used drugs to target one class of the so called GABA-A receptor. They found that by activating this target produces "pronounced analgesia" without unwanted sedation and without paralysis. Nor did mice build up a tolerance to treatment, unlike with many drugs.

The team go on to show that brain activity in rats in areas related to feeling pain is much reduced when they received the same treatment. However, Prof Zeilhofer said that it is still too early to say when this new understanding will produce new treatments.

Chronic pain is sometimes linked with an initial mishap - sprained back, serious infection - or there may be an ongoing cause of pain - arthritis, cancer, and ear infection. However, some people suffer chronic pain in the absence of any past injury or evidence of body damage.

Last year, an American team found a "magic bullet" to train pain without causing numbness. Childbirth, surgery and trips to the dentist might be less traumatic in the future, thanks to a team at Massachusetts General Hospital and Harvard Medical School, Boston, which has achieved the feat in the laboratory by adding spice to an anaesthetic that by itself should not work because it does not get into nerves.

The sense of pain was selectively switched off in rat hindpaws by injecting QX-314, a normally inactive derivative of the commonly used local anaesthetic lignocaine, and capsaicin, the heat generating ingredient in chilli peppers.

In combination, these chemicals targeted only pain-sensing nerve cells, preventing them from sending signals to the brain. But even though the rats could not feel pain in their paws, they continued to move normally and react to touch.

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