Opioids may prolong chronic pain, study suggests

Opioids are prescribed to help prevent chronic pain, but study results released Monday suggest these painkillers may actually do the opposite of their intention. Researchers, who published their findings in the journal Proceedings of the National Academy of Sciences, said that although their findings were drawn from mice, their observations may have implications for humans amid an opioid abuse epidemic in the United States that killed an estimated 20,000 Americans in 2015.

Study authors at the University Colorado Boulder found that only five days of morphine treatment caused chronic pain that persisted for several months by worsening pain signals from certain immune cells in the spinal cord.

"We are showing for the first time that even a brief exposure to opioids can have long-term negative effects on pain," lead study author Peter Grace, an assistant research professor in psychology and neuroscience at CU-Boulder, said in a news release. "We found the treatment was contributing to the problem."

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Researchers observed that a peripheral nerve injury in rats relayed a signal from damaged nerve cells to spinal cord immune cells known as glial cells, which are supposed to help clear unwanted debris. The first signal of pain triggers glial cells for further action, but five days of opioid treatment sends them into overdrive, leading to spinal cord inflammation, among other consequences.

"This one-two hit causes the glial cells to explode into action, making pain neurons go wild,” study author Linda Watkins, a distinguished professor in psychology and neuroscience, said in the release.

This effect, which Watkins likened to slapping a person’s face, set off a cascade of cell signals to produce a cell signal from a protein called inter-leukin-1beta (IL-1b), which activates pain-responsive nerve cells in the spinal cord and brain, prolonging pain duration.

"The implications for people taking opioids like morphine, oxycodone and methadone are great, since we show the short-term decision to take such opioids can have devastating consequences of making pain worse and longer lasting," Watkins said in the release. "This is a very ugly side to opioids that had not been recognized before."

But on the plus-side, researchers have identified ways to block certain receptors on glial cells that recognize opioids, and in turn relieve pain and prevent chronic pain. According to the release, researchers at CU-Boulder did just that using the designer drug technology DREADD to target and turn off glial cells for the first time.