Opioids After Surgery Can Lead To Chronic Pain: Study

BOULDER, CO -- A new study from the University of Colorado at Boulder shows opioids prescribed for pain after surgery may actually do more harm than good. Giving opioids to animals after surgery turns out to prolong pain for more than three weeks, the study showed. Furthermore, opioid use appeared to "prime specialized immune cells in the spinal cord to be more reactive to pain," the study showed.

“This indicates that there is another dark side of opiates that many people don’t suspect,” said senior author Linda Watkins, a professor in the Department of Psychology and Neuroscience in a press release. “It shows that trauma, including surgery, in combination with opiates can lead to chronic pain.”

Researchers in the study performed "exploratory abdominal surgery" on male rats and gave them morphine for pain relief afterwards. The study, reported in Anesthesia and Analgesia, found:

• Rats given a moderate dose of morphine for seven days after surgery experienced post-operative pain for three weeks longer than those not given morphine.
• The longer the rats received morphine, the longer their pain was prolonged.
• Opioids on top of surgery represent a "one-two" hit which creates an enduring state of inflammation and can lead to chronic pain.

“Opiates are really effective for acute pain relief. There is no drug that works better. But very little research has been done to look at what it is doing in the weeks to months after it’s withdrawn,” said the study's co-author, Peter Grace, now an assistant professor at MD Anderson Cancer Center in Houston.

The study was described in a press release:

In one experiment, half the rats were given the equivalent of what would be a “moderate” dose of morphine in people for seven days postsurgery. Half were given a saline solution.

In another experiment, the rats were given morphine for eight days and then tapered off by day 10. In a third, the animals were given morphine until day 10 and then it was abruptly withdrawn.

Before and after the treatments, the researchers measured the animal’s sensitivity to touch as well as activity of genes that express inflammatory proteins in the spinal cord.

They found that rats given morphine experienced postoperative pain for more than three weeks longer. The longer they received morphine, the longer their pain lasted. And gradual tapering made no difference.

“This tells us that this is not a phenomenon related to opioid withdrawal, which we know can cause pain. Something else is going on here,” Grace said.

In a previous study, published in 2016, rats were found to experience swelling and chronic pain for months after just a few days of treatment with opiates to treat peripheral nerve pain, such as sciatica.

Watkins said this new study provides a partial explanation for a few small studies in humans which have associated postsurgical opioid administration with chronic pain as much as one year later. Chronic pain is experienced by more than 50 million people in the U.S., according to the National Institutes of Health.

Research done by the New York Times and ProPublica shows that U.S. doctors and insurance companies also have an economic incentive to prescribe opioids: They are generally cheaper than some less-addictive pain killers.

The studies by CU researchers show the "great irony" of prescribing opioids for postoperative pain that may end up causing chronic pain, Watkins said.

“An unusually high number of people end up with postoperative chronic pain. This new study lends insight into one explanation for that,” Watkins said.

Watkins is also studying new compounds that could be given with opioids to "mute the exaggerated immune response they are believed to trigger." Researchers are also studying alternative painkillers, including cannabinoids, for pain.

“There is surely a dark side in terms of addiction when it comes to opioids, but this is a very different idea—that we think we are treating the pain with these drugs and we may actually be prolonging it.” Watkins said.

Read more about CU's earlier research here.

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