Pain Paradox: Opioid Painkillers Prolong Chronic Pain In Rats

A new study conducted by researchers at the University of Colorado Boulder, has found that opioids, like morphine, paradoxically increase the pain response in rats. With the dramatic rise in cases of opioid abuse in the US, these findings could have an impact on how these painkillers are prescribed.

According to the study leaders – University of Colorado Boulder Assistant Research Professor Peter Grace, and Distinguished Professor Linda Watkins – rats that were treated with morphine for less than one week experienced chronic pain that lasted for several months. The researchers say that increased opioid use in humans could be exacerbating chronic pain by enhancing the release of pain signals from immune cells in the spinal cord.

“We are showing for the first time that even a brief exposure to opioids can have long-term negative effects on pain,” said Grace. “We found the treatment was contributing to the problem.”

The study – which was published in the journal, PNAS – looked at peripheral nerve injury in rats, and found that the damaged nerve cells submit a message to the immune cells of the spinal cord, known as glial cells. Once the signal is received, these glial cells become primed to receive further signals and begin to respond to the source of injury.

Grace explains the reaction by saying, “I look at it like turning up a dimmer switch on the spinal cord.” When Grace and his colleagues treated the injury with a 5-day course of opioids, the glial cells initiated a host of cascade reactions, including inflammation of the spinal cord.

Watkins describes the process as a two-hit reaction: the initial pain signal is the first hit, with the subsequent opioid treatment acting as the second. “This one-two hit causes the glial cells to explode into action, making pain neurons go wild.”

The research team discovered that the peripheral nerve damage coupled with the short course of treatment with opioid painkillers, was sufficient to trigger the glial cell signaling cascade response. One of the products of the cell signal cascade – a protein known as interleukin-1beta – acts on nerve cells in the spinal cord and the brain, making them more responsive to pain signals. This interaction is what causes chronic pain, which 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,” said Watkins. “This is a very ugly side to opioids that had not been recognized before.”