In recent years, the rising use of painkillers and dangers of addiction and overdose have made their way into the spotlight, causing doctors to curb prescriptions for these drugs. Now, a new study reveals that opioids like morphine actually increase chronic pain in lab rats, which could have huge implications for their use on humans.
The study - led by the University of Colorado (UC) Boulder - shows that a few days of morphine treatment in rats causes chronic pain that lasts for several months, an effect caused by an increase in the release of pain signals from immune cells in the spinal cord.
The findings highlight the possibility that prescription opioids could actually be increasing chronic pain in humans instead of treating it.
"We are showing for the first time that even a brief exposure to opioids can have long-term negative effects on pain," said Peter Grace of UC Boulder and co-lead author of the study. "We found the treatment was contributing to the problem."
During the course of the experiment, the team examined peripheral nerve injuries in rats. These injuries send messages from the damaged cells to spinal cord immune cells called glial cells, which are "cleaning" cells that remove unwanted debris. After receiving the first pain signals, they enter an alert mode in case further action needs to be taken.
"I look at it like turning up a dimmer switch on the spinal cord," Grace said.
However, after just five days of opioid treatment, Grace and his team found that glial cells went into a state of increased excitation, leading to numerous consequences including spinal cord inflammation. The results suggest that just like the initial pain signals to the spinal cord, morphine treatment puts the glial cells into alert mode.
"You might get away with the first slap, but not the second," said Linda Watkins of UC Boulder, also co-lead author of the study. "This one-two hit causes the glial cells to explode into action, making pain neurons go wild."
Further examination revealed that this cascade of glial cell signals creates a protein called interleukin-1beta (IL-1b), which leads to an increase in nerve cells connected to pain responses in the spinal cord and brain. This increase in IL-1b can cause increases in pain duration that can last for 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," Watkins said. "This is a very ugly side to opioids that had not been recognized before."
The findings were published in the Proceedings of the National Academy of Sciences.
