Morphine makes chronic nerve pain worse, according to a new animal study, but some experts question whether its findings are relevant to humans.
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Researchers writing this week in the Proceedings of the National Academy of Sciences report that rats given morphine took longer to recover from injury and had more severe pain.
This effect lasted for up to two to three months in rats after they were treated for just five days with morphine, co-author Dr Peter Grace, an Australian neuroscientist at the University of Colorado, said.
“The treatment can actually be contributing to the problem,” he said.
Dr Grace said animal studies over the past 30 years had shown that glial cells in the immune system release neurotransmitters that stimulate pain neurones.
Other studies had shown that opioids like morphine also activate those same cells, he said.
Putting two and two together, Dr Grace and his colleagues hypothesised that injured rats would end up having worse pain when treated with morphine.
Experiments test pain sensitivity
In their experiments they pinched the sciatic nerve in the legs of male rats, which caused the animals to develop inflammation and pain. The rats were then treated with morphine for five days.
At various times after the treatment was stopped, the researchers pricked the animals’ hind paws to test their pain sensitivity.
“The rats that had received the injury but no morphine recovered after about four to five weeks like we expected,” Dr Grace said.
“But those rats that were treated with morphine had a doubling of the duration of their chronic pain. It took them 10 or 11 weeks to recover.”
Previous animal research has shown that while morphine works initially, it loses its effectiveness, Dr Grace said.
“It seems morphine works quite well initially, but as the immune system ramps up, this starts to oppose the pain-relieving properties of morphine and morphine starts to induce pain in its own right.”
Dr Grace said the findings could help explain why some individuals develop a tolerance to morphine.
In a second part of the study, Dr Grace and colleagues used a drug to block the glial cells and found this switched off the pain-amplifying effects of morphine.
In future the team hopes to test whether the effect also occurs in female rats, with different types of opioid drugs, and with different types of pain.
Senior author of the paper, Dr Linda Watkins, is on the scientific advisory board of a company developing a drug that could do this in humans.
Human pain is a “complex phenomenon”
University of Sydney’s pain management expert Dr Paul Glare said better understanding how opioids work was important given they were not always effective.
“Opioids aren’t a panacea for all pain management,” he said.
“[The new research] may help identify which patients won’t benefit from them.”
However Dr Glare said there were difficulties transferring the findings in animals to humans.
“This kind of thing looks very promising but it doesn’t always amount to something that makes a difference to people with pain.”
Dr Glare said a patient’s experience of pain was a “complex phenomenon” that included psychological, social, environmental, and biomedical factors.
While acknowledging the limitations of opioids, Dr Mark Connor, a professor of pharmacology at Macquarie University, was not convinced by the idea that morphine can effect humans in the way seen in the rat experiment.
“There is no evidence for this kind of dramatic prolonging of neuropathic pain for a relatively short opioid exposure in humans,” he said.
He said if opioids did work in the way suggested, this could explain symptoms of opioid tolerance.
But the evidence that morphine activates glial cells is unclear, said Dr Connor.
“It’s still an area of some controversy.”
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