Researchers are closer to finding out the reason why certain adults and children’s pain gets worse when they treated with morphine.
“Our research identifies a molecular pathway by which morphine can increase pain, and suggests potential new ways to make morphine effective for more patients,” senior author Dr. Yves De Koninck, Professor at Universite Laval in Quebec City said.
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 research not only identifies a target pathway to suppress morphine-induced pain but teases apart the pain hypersensitivity caused by morphine from tolerance to morphine, two phenomena previously considered to be caused by the same mechanisms.
“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. But sometimes increasing the morphine can, paradoxically, makes the pain worse,” co-author Dr. Michael Salter, Senior Scientist and Head of Neurosciences and Mental Health at SickKids, Professor of Physiology at University of Toronto, and Canada Research Chair in Neuroplasticity and Pain said.
“Pain experts have thought tolerance and hypersensitivity (or hyperalgesia) are simply different reflections of the same response,” Dr. De Koninck said, “but we discovered that cellular and signalling processes for morphine tolerance are very different from those of morphine-induced pain.”
Dr. Salter added, “We identified specialized cells – known as microglia – in the spinal cord as the culprit behind morphine-induced pain hypersensitivity. When morphine acts on certain receptors in microglia, it triggers the cascade of events that ultimately increase, rather than decrease, activity of the pain-transmitting nerve cells.”
The researchers also identified the molecule responsible for this side effect of morphine.
“It``s a protein called KCC2, which regulates the transport of chloride ions and the proper control of sensory signals to the brain,” Dr. De Koninck said.
“Morphine inhibits the activity of this protein, causing abnormal pain perception. By restoring normal KCC2 activity we could potentially prevent pain hypersensitivity.”
The research is published in the on-line edition of Nature Neuroscience.