Morphine Can Increase Pain In Some Patients, But Why?
January 7, 2013

Study Reveals Why Morphine Can Increase Pain In Some Patients

redOrbit Staff & Wire Reports - Your Universe Online

While morphine is typically used by doctors to relieve pain, it can inexplicably have the opposite effect on some patients. Now, a team of researchers is close to pinpointing the biological causes of the phenomenon known as morphine-induced pain hypersensitivity.

Researchers from Université Laval in Quebec City, The Hospital for Sick Children (SickKids) in Toronto, and the Institut universitaire en santé mentale de Québec, as well as colleagues from Italy and the US, have identified "a molecular pathway by which morphine can increase pain," senior author Dr. Yves De Koninck, a professor at Université Laval, said Sunday in a statement.

The research, which has been published in the latest online edition of the journal Nature Neuroscience, could also lead to new ways to make the pain-relieving medication effective for a greater number of patients, De Koninck added.

Furthermore, it has also lead to the discovery that resistance to morphine and hypersensitivity to it are not caused by the same biological mechanisms, as had previously been believed.

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

"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," added co-author Dr. Michael Salter, chief of Neurosciences & Mental Health at SickKids and a physiology professor at University of Toronto.

The molecule responsible for the side effect, according to De Koninck, Salter, and their colleagues, is KCC2, a protein which regulates the transportation of chloride ions and oversees sensory signals sent to the brain.

Taking morphine inhibits KCC2's activity, altering a person's perception of pain -- a phenomenon which could be prevented if scientists can devise a way to restore the protein to normal levels of activity. Thus, researchers at Université Laval, are currently testing new molecules that are "capable of preserving KCC2 functions and thus preventing hyperalgesia," the institution said.

"Our discovery could have a major impact on individuals with various types of intractable pain, such as that associated with cancer or nerve damage, who have stopped morphine or other opiate medications because of pain hypersensitivity," Salter added. "Too often, patients with chronic pain feel abandoned and stigmatized. Among the many burdens on individuals and their families, chronic pain is linked to increased risk of suicide."