Researchers have questioned the pain-relieving effects of opioids.
Study co-leader Prof. Peter Grace, of the University of Colorado at Boulder (CU-Boulder), and colleagues recently published their findings in the Proceedings of the National Academy of Sciences.
Opioids are among the most commonly used painkillers in the United States; almost 250 million opioid prescriptions were written in 2013 - the equivalent to one bottle of pills for every American adult.
Previous studies have suggested opioids - such as codeine, oxycodone, morphine, and fentanyl - are effective pain relievers. They bind to proteins in the brain, spinal cord, and gastrointestinal tract called opioid receptors, reducing pain perception.
Increasing use and abuse of opioids, however, has become a major public health concern in the U.S.; opioid overdoses are responsible for 78 deaths in the country every day.
Now, Prof. Grace and colleagues have questioned whether opioids really work for pain relief, after finding the opioid morphine worsened chronic pain in rats.
Just 5 days of morphine treatment increased chronic pain in rats
According to Prof. Grace, previous studies assessing morphine use have focused on how the drug affects pain in the short term.
With this in mind, the researchers set out to investigate the longer-term effects of morphine use for chronic pain.
For their study, the team assessed two groups of rats with chronic nerve pain. One group was treated with morphine, while the other was not.
Compared with the non-treatment group, the team found that the chronic pain of the morphine group worsened with just 5 days of treatment. What is more, this effect persisted for several months.
"We are showing for the first time that even a brief exposure to opioids can have long-term negative effects on pain," says Prof. Grace. "We found the treatment was contributing to the problem."
Another 'ugly side' to opioids
According to the authors, the combination of morphine and nerve injury triggered a "cascade" of glial cell signaling, which increased chronic pain.
They found that this cascade activated signaling from a protein called interleukin-1beta (IL-1b), which led to overactivity of nerve cells in the brain and spinal cord that respond to pain. This process can increase and prolong pain.
The researchers say their findings have important implications for individuals with chronic pain - a condition that is estimated to affect around 100 million Americans.
"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."
Study co-leader Prof. Linda Watkins, CU-Boulder
It is not all bad news, however. The researchers found they were able to reverse morphine's pain-increasing effect using a technique called "designer receptor exclusively activated by designer drugs" (DREADD), which involves the use of a targeted drug that stops glial cell receptors from recognizing opioids.
"Importantly, we've also been able to block the two main receptors involved in this immune response, including Toll-Like receptor 4 (TLR4) and another one called P2X7R, which have both been separately implicated in chronic pain before," notes Prof. Grace.
"By blocking these receptors, we're preventing the immune response from kicking in, enabling the painkilling benefits of morphine to be delivered without resulting in further chronic pain."
He adds that drugs that can block such receptors are currently in development, but it is likely to be at least another 5 years before they are available for clinical use.