The study led by researchers from University of Colorado Boulder in US showed that just a few days of morphine treatment caused chronic pain that went on for several months by exacerbating the release of pain signals from specific immune cells in the spinal cord.
    
The results suggest that the recent escalation of opioid prescriptions in humans may be a contributor to chronic pain, researchers said.

"We are showing for the first time that even a brief exposure to opioids can have long-term negative effects on pain. We found the treatment was contributing to the problem," CU-Boulder Assistant Research Professor Peter Grace said.

The study showed that a peripheral nerve injury in rats sends a message from damaged nerve cells to spinal cord immune cells known as glial cells, which normally act as "housekeepers" to clear out unwanted debris and microorganisms.

The first signal of pain sends glial cells into an alert mode, priming them for further action.

When the injury was treated with just five days of opioids the glial cells went into overdrive, triggering a cascade of actions, including spinal cord inflammation.

According to Professor Linda Watkins, the initial pain signals to the spinal cord and the subsequent morphine-induced treatment is a two-hit process, which she likened to slapping a person's face.

"You might get away with the first slap, but not the second. This one-two hit causes the glial cells to explode into action, making pain neurons go wild," she said.

The team discovered that the pain signals from a peripheral injury combined with subsequent morphine treatment worked together to cause a glial cell signalling cascade.
    
The cascade produces a cell signal from a protein called interleukin-1beta (IL-1b), which increases the activity of pain-responsive nerve cells in the spinal cord and brain. That can cause increases in pain duration lasting several months.

"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," said Watkins.

"This is a very ugly side to opioids that had not been recognised before," she said.

The researchers have found ways to block specific receptors on glial cells that recognise opioids. This could allow for some pain relief while potentially preventing chronic pain.

The team used a designer drug technology known as DREADD to selectively turn off targeted glial cells, something that has not been done before, Grace added.

The study was published in the journal PNAS.

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