Opioids Can Extend Pain

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Anyone who's had major surgery has a deep appreciation for opioids, a type of pain killer. The problem is when someone can't stop taking them. Here's the irony though. A new study suggests the more opioids you take, the less it works. The reason is an effect called hyperalgesia. Hyperalgesia may cause us higher sensitivity to pain even after the injury has healed.

To better understand it, a recent study worked with rats by mimicking chronic pain in humans. They tied a fine thread around a major nerve in the thigh that eventually dissolves. After the surgery, half the rats were given the opioid morphine and half went without.

Over the next three months, the rats' sensitivity to pain was measured by sticking their paws with wires of various sharpness. The results showed that the non-medicated rats were sensitive to pain for a limited period of time. But the rats given morphine continued to experience high pain sensitivity for 12 weeks before it returned to normal.

So, why would opioids prolong the recovery from pain? The researchers propose there are two hits on microglia which are immune cells in the central nervous system that respond to injury. The first hit is the injury, for example, to the nerve. That activates the microglia and triggers a whole series of events to deal with the injury.

But if opioids are given, they end up acting as a second hit for unknown reasons. They exaggerate the nerve inflammation by amplifying the signal which for the person ends up feeling like persistent pain.

We need to confirm whether this same process happens in humans. If opioids set off a chain of immune reactions in the spinal cord that actually prolongs and amplifies pain even after drug treatment is stopped, we will need new protocols for pain management.

More Information

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Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation
P.M. Grace, et al. Proceedings of the National Academy of Science of the United States of America. 2016 Jun 14;113(24):E3441-50

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