Narcotic painkillers prolong pain in rats, study finds

May 30, 2016, University of Colorado at Boulder
A new University of Colorado Boulder study shows narcotic painkillers can cause chronic pain in rats. Credit: University of Colorado

The dark side of painkillers - their dramatic increase in use and ability to trigger abuse, addiction and thousands of fatal overdoses annually in the United States is in the news virtually every day.

Brace for another shot across the bow: Opioids like morphine have now been shown to paradoxically cause an increase in chronic in lab rats, findings that could have far-reaching implications for humans, says a new study led by the University of Colorado Boulder.

Led by CU-Boulder Assistant Research Professor Peter Grace and Distinguished Professor Linda Watkins, the study showed that just a few days of morphine treatment caused chronic pain that went on for several months by exacerbating the release of from specific immune cells in the . The results suggest that the recent escalation of opioid prescriptions in humans may be a contributor to chronic pain, said Grace.

"We are showing for the first time that even a brief exposure to can have long-term negative effects on pain," said Grace, who is a faculty member along with Watkins in CU-Boulder's Department of Psychology and Neuroscience. "We found the treatment was contributing to the problem."

A paper on the study was published May 30 in the Proceedings of the National Academy of Sciences.

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.

"I look at it like turning up a dimmer switch on the spinal cord," said Grace.

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. Watkins said 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," she said. "This one-two hit causes the glial cells to explode into action, making pain neurons go wild."

The team discovered that the pain signals from a peripheral injury combined with subsequent morphine treatment worked together to cause a glial cell signaling cascade. The cascade produces a cell signal from a protein called interleukin-1beta (IL-1b), which increases the activity of pain-responsive 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 recognized before."

Roughly 20,000 Americans died in 2015 from overdoses of prescription opioid pain relievers, according to the National Institute on Drug Abuse.

On the up side, the researchers have found ways to block specific receptors on glial that recognize opioids. This could allow for some pain relief while potentially preventing . The team used a designer drug technology known as DREADD to selectively turn off targeted , something that has not been done before, said Grace.

Explore further: Using morphine after abdominal surgery may prolong pain, researchers find

More information: Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation, PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1602070113

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3 comments

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24volts
1 / 5 (2) May 30, 2016
Just because that's the way rats respond does not mean that's the way humans respond. That has been proven over and over again. It doesn't affect humans that way and I should know. I've been disabled since 1989 with pain and having pain killers on hand doesn't make it worse. I've never heard of pain killers making pain worse for anyone.
Anonym
3 / 5 (2) May 31, 2016
Well, opiods are "in the news virtually every day" because something is required for the drug warriors to police, since that they no longer have marijuana users to kick around any more. Phony crises are the basis, apparently, of all governance these days, and the opiod "crisis" is about as phony as they come.
Captain Stumpy
5 / 5 (1) Jul 07, 2016
@24volts
I've been disabled since 1989
well THAT sucks...
but i know what you're going thru
I've never heard of pain killers making pain worse for anyone
this depends on if you want to stop the pain killers and the feedback pains of habitual addiction, regardless of manifested addiction issues you may or may not have noticed, especially with long term use of pain killers

case in point: opioid hydrocodone (Vicodin/Hydrocodone/Paracetamol)
this can alleviate pain well enough but once you've taken it for long enough (dependent upon your body, mass, metabolism and other factors) then stopping the drug can cause greater pain than it was prescribed to alleviate

there have been similar cases to long term use of the "so called" non-habit forming Tramadol/ConZip/Ultram

studies indicate there can also be long term effects like liver damage (see: acetaminophen) which can cause pain not related to the initial prescribed treatment reasons

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