By Deborah Fields, BSc (Hons), PgDip, MCIPR
Painkillers such as morphine, oxycodone and methadone could actually prolong and increase pain even after only a few days’ use, according to research conducted on rats by scientists at the University of Colorado Boulder in the US.
Published in the Proceedings of the National Academy of Sciences on 30th May, the findings about the narcotics could have an impact on how humans are prescribed the painkillers. Opioid abuse is believed to affect between 26.4 million and 36 million people worldwide. The drugs impact the same areas of the brain as heroin. In the US in 2015, about 20,000 people had overdoses from prescription opioid painkillers.
The research, led by University of Colorado Boulder’s Assistant Research Professor Peter Grace and Distinguished Professor Linda Watkins of the Department of Psychology and Neuroscience, found that only a few days of exposure to the morphine in the rats could result in increased chronic pain for several months. In particular, it led to the rats producing pain signals from immune cells in the spinal cord.
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,”
“This is a very ugly side to opioids that had not been recognized before.”
Professor Linda Watkins, Department of Psychology and Neuroscience, University of Colorado Boulder.
Grace added about the research: “We are showing for the first time that even a brief exposure to opioids can have long-term negative effects on pain,” he said. “We found the treatment was contributing to the problem.”
The scientists observed that damage to the peripheral nerve in a rat results in messages from the injured nerve cells to the supportive glial cells in the spinal cord that protect neurons in the nervous system. The glial cells are sent into panic and are then ready for further impact.
“I look at it like turning up a dimmer switch on the spinal cord,” said Grace.
The scientists then treated the damaged area with opioids for five days with the glial cells still extremely activated and further reactions following such as spinal cord inflammation. The researchers described it as the original pain being the first hit to the system and then the morphine treatment causing a second hit similar to slapping a person’s face which then continues for months.
“You might get away with the first slap, but not the second,” Watkins said. “This one-two hit causes the glial cells to explode into action, making pain neurons go wild.”
The combination of the injury and then the treatment with morphine created a landslide of glial cell signaling from the interleukin-1beta (IL-1b) which elevates activity of the pain-responsive nerve cells in the spinal cord and brain.
In addition, the scientists have identified a way of shielding the receptors on the glial cells that recognize the opioids. This could help to reduce the chronic pain. They used the designer drug technology DREADD, engineered G-protein coupled receptors, to turn off specific glial cells.
Professor Hubert Yin of CU-Boulder’s BioFrontiers Institute as well as researchers from the University of Adelaide in Australia, the University of North Carolina, the Chinese Academy of Sciences, the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and Tsinghua University in Beijing were all involved in the study.
The American Pain Society, Australia’s National Health and Medical Research Council, the National Natural Science Foundation in China, the National Institute on Drug Abuse, the National Institute of Dental and Craniofacial Research and the National Institute of Alcohol Abuse and Alcoholism all part funded the study.
References
- National Institute on Drug Abuse on opioids
- DREADD wiki on the DREADD technology
- EurekAlert! Public release on Narcotic painkillers prolong pain in rats, says CU-Boulder study