Published online 13 November 2006 | Nature | doi:10.1038/news061113-4

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Compound in saliva could be more powerful than morphine.

Doctors may have a new natural weapon to fight pain. Punchstock

A new painkilling substance has been discovered that is up to six times more potent than morphine when tested in rats — and it's produced naturally by the human body. Natural painkillers are very rare, and researchers hope that this recent find might be harnessed as a clinical treatment.

Naturally produced painkillers might help to avoid some of the side effects experienced by patients treated with synthetic compounds such as morphine, including addiction and tolerance with prolonged use. But the new substance will first have to be tested to confirm whether it will be an effective drug, experts warn.

The compound, dubbed opiorphin, seems to work by prolonging the body's own defences against pain, explain Catherine Rougeot of the Pasteur Institute in Paris, France, and her colleagues, who report the discovery in Proceedings of the National Academy of Sciences1. It does so by preventing the breakdown of chemicals called enkephalins, which in turn activate opiate receptors that block pain signals from reaching the brain.

Rougeot's team tracked down the new compound after previously finding a similar natural painkiller in rats, called sialorphin2. They wondered whether humans might produce something similar — and by analysing saliva samples, hit upon opiorphin.

This is the first natural substance to be found in humans that exploits this mechanism to relieve pain. But it's unlikely that opiorphin ordinarily has a painkilling role in the body, says Alistair Corbett, a specialist on opioids at Glasgow Caledonian University, UK. The substance could play a general role in protecting chemicals in the body from being broken down, he says.

Kissing it better

Opiorphin seems to work on pain induced by both chemical and physical means. When it was given to rats that had been given a painful injection, they exhibited diminished pain responses, such as licking the injected paw. It also reduced acute pain when the rats walked across a pin-covered surface, Rougeot and her colleagues report.

Researchers have previously tried to make synthetic compounds to perform the same function of protecting enkephalins, with little success. "Inhibiting this enzyme would be a good target for drugs. But nobody has looked for a natural inhibitor," Rougeot says.

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But Sandy McKnight, formerly associate director of the Parke-Davis Neuroscience Research Centre in Cambridge, UK, sounds a cautionary note: "The area has already been very thoroughly researched. In spite of this effort, no such drug has yet reached clinical trial, and it is unlikely that the description of opiorphin will be seen as much of a stimulus for chemists to redouble their efforts."

A substance like opiorphin is unlikely to be specific enough to protect the breakdown of enkephalins alone, he adds. This means that the compound might have unforeseen side effects.

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