Animals that were given opioids to reduce their pain after surgery ended up prolonging their pain for more than 3 weeks and primed specialized immune cells in their spinal cord to be more reactive to pain, according to researchers.
The researchers, from the University of Colorado Boulder, suggest that, if replicated in humans, these findings could have implications for patient pain management and could lead to chronic pain.
“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 media release from University of Colorado at Boulder. “It shows that trauma, including surgery, in combination with opiates can lead to chronic 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,” she adds.
In the study, published in Anesthesia & Analgesia, Watkins and co-author Peter Grace, then an assistant research professor at CU Boulder, performed exploratory abdominal surgery, or laparotomy, on male rats.
In one experiment, half the rats were given the equivalent of what would be a “moderate” dose of morphine in people for 7 days postsurgery. Half were given a saline solution.
In another experiment, the rats were given morphine for 8 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 In a third, the animals were given morphine until day 10 and then it was abruptly withdrawn.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 3 weeks longer. The longer they received morphine, the longer their pain lasted. And gradual tapering made no difference, according to the release.
“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 states.
Watkins describes that something as a “one-two hit” on specialized immune system cells called glial cells in the central nervous system. The first hit, the surgery, stimulates what she calls the “not me, not right, not OK” receptor, Toll-like receptor 4 on the cells, igniting the release of a cascade of inflammatory proteins and “priming” them to be on guard for a second hit.
Morphine, which also stimulates that receptor, is the second hit.
“With that second hit, the primed glial cells respond faster, stronger and longer than before, creating a much more enduring state of inflammation and sometimes local tissue damage,” she continues, in the release.
The researchers, acknowledging that animal studies cannot directly translate to humans, are now calling for more clinical studies on opioids and chronic pain.
[Source(s): University of Colorado at Boulder, Science Daily]