New research has found why morphine, a pain reliever, increases pain in some patients. Researchers say the study even identified a target pathway that could suppress morphine-induced pain.

"Our research identifies a molecular pathway by which morphine can increase pain, and suggests potential new ways to make morphine effective for more patients," said Dr. Yves De Koninck, Professor at Université Laval in Quebec City and senior author of the study.

Dr. Michael Salter from University of Toronto explained that when morphine doesn't relieve pain, doctors increase the dosage that can cause more pain. Some people actually require more morphine than others because they have a higher tolerance for the drug, but in few others, morphine can increase the pain. The study found mechanisms that explain morphine tolerance as well as the increase in pain.

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

Researchers found that microglia - specialized cells in the spinal cord - are the reason behind the hypersensitivity to pain induced by morphine. Activation of certain receptors in microglia increases pain rather than decrease it.

The study also found the molecule that was responsible for the increase in pain.

"It's a protein called KCC2, which regulates the transport of chloride ions and the proper control of sensory signals to the brain. Morphine inhibits the activity of this protein, causing abnormal pain perception. By restoring normal KCC2 activity we could potentially prevent pain hypersensitivity," said Dr. De Koninck.

Dr. De Koninck added that the KCC2 pathway can help explain pain that is associated with both short-term and long-term morphine use thus opening up new ways to treat both post-operative and chronic pain.

The study can help reduce pain in people who suffer from pain associated with cancer, nerve damage and those who have stopped using morphine to their hypersensitivity, Dr. Salter added.

The study is published in the journal Neuroscience.

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