Excessive dependence on narcotic painkillers has long been an enemy of public health, but the dark side of opioid use doesn't end there.

New research suggests that drugs that are supposed to offer relief can actually make a person more sensitive to pain overtime — an effect known as hyperalgesia.

Led by scientists from University of Colorado Boulder (CU-Boulder), the new study investigated the long-term effects of opioid treatment, specifically morphine, in lab rats.

How Increase In Opioid Use Affected Lab Rats

Neuroscientist Peter Grace, one of the lead authors of the study, says the link between opioid and pre-existing pain has been poorly studied, but they have been trying to trace hyperalgesia to how opioids affect the immune system.

Grace and his colleagues used a rat model to mimic chronic nerve pain found in humans. This is the kind of condition that many experience from stroke, traumatic nerve injury or nerve damage caused by diabetes.

The researchers sliced into the thighs of the rats and tied a fine thread around a major nerve. The thread swelled as time passed by in order to cause painful constriction in the nerve. The thread dissolved after six weeks.

Ten days after, half of the lab rats received a treatment of morphine for five days. For about three months, Grace and his team periodically measured the rats' threshold of pain by poking their hind paws with nylon threads of different thicknesses.

Researchers say the finer the thread that causes the rat to withdraw shows the more sensitive it is to pain.

After six weeks, injured lab rats that did not receive morphine all withdrew from the same kind of pokes as the uninjured rats.

However, when it came to morphine-treated lab rats, they were more sensitive to pokes with much finer hair. It took at least 12 weeks before these rats returned to the same pain sensitivity threshold as the other rats.

As it turns out, opioids can paradoxically cause an increase in chronic pain that can go on for a long time. In fact, just a few days of morphine treatment already caused higher sensitivity to pain.

This happened because the morphine worsened the release of pain signals from certain immune cells in the spinal cord, researchers say.

Specifically, a protein named interleukin-1beta (IL-1b) boosts the motion of pain-responsive nerve cells in the brain and spinal cord. This can make pain last longer.

What's Next?

Grace says their findings suggest that increasing opioid prescriptions in humans may even be a contributor to chronic pain.

"We found the treatment was contributing to the problem," says Grace, who is also an associate professor at CU-Boulder.

He says short-term decisions to take morphine, oxycodone and other opioids could have very ugly consequences, making pain longer lasting and worse.

On the bright side, Grace and his team are already working on drugs that could block receptors on glial cells that identify opioids. This could result in pain relief while preventing chronic pain. Grace adds that the field needs a human study to systematically test pain thresholds over time.

The findings of the study are published in the journal PNAS.

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