Solution to morphine's side-effect in sight

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Toronto, Jan 7 (IANS) Popular painkiller drug morphine comes with a devastating side-effect, inflicting greater pain on users rather than easing their agony. But this could hopefully be a thing of the past, says a study that found new ways to make the drug more effective.

"Our research identifies a molecular pathway by which morphine can increase pain, and suggests potential new ways to make morphine effective for more patients," says senior author Yves De Koninck, professor at Universite Laval in Quebec City, Canada.

The team included researchers from the Hospital for Sick Children (SickKids) in Toronto, the Institut Universitaire en Sante Mentale de Quebec, the US and Italy, the journal Nature Neuroscience reports.

Pain has been labelled the silent health crisis, afflicting tens of millions of people worldwide. Pain has a profound negative effect on the quality of human life, according to a Laval statement.

"When morphine doesn't reduce pain adequately, the tendency is to increase the dosage. If a higher dosage produces pain relief, this is the classic picture of morphine tolerance, which is very well known," explains study co-author Michael Salter.

"But sometimes increasing the morphine can, paradoxically, make the pain worse," adds Salter, senior scientist and head of neurosciences and mental health, at SickKids and professor of physiology at University of Toronto.

"Pain experts have thought tolerance and hypersensitivity (or hyperalgesia, sensitivity to pain) are simply different reflections of the same response," says De Koninck, "but we discovered that cellular and signalling processes for morphine tolerance are very different from those of morphine-induced pain."

Researchers also identified the molecule behind morphine side-effect as "a protein called KCC2, which regulates the transport of chloride ions and the proper control of sensory signals to the brain," says De Koninck.

"Morphine inhibits the activity of this protein, causing abnormal pain perception. By restoring normal KCC2 activity we could potentially prevent pain hypersensitivity."

De Koninck and researchers at Universite Laval are testing new molecules capable of preserving KCC2 functions and thus preventing hyperalgesia.