Do Opioid Painkillers Actually Make Users More Sensitive to Pain?

Over the past few years, the number of opioid overdose deaths in the USA has hit epidemic levels. This has thrown prescription painkillers into the spotlight, with a new study heightening concerns surrounding opioid drugs like morphine and oxycodone. According to researchers, studies conducted on mice show that these types of medications can actually increase sensitivity to pain.

For the most part, opioid drugs are considered extremely effective painkillers as they actively bind to receptors in the brain and central nervous system. In turn, this minimises the body’s neural response to painful stimuli. This is a widely accepted neurological fact, yet a new study published by Proceedings of the National Academy of Sciences is now suggesting that while opioids may alleviate acute pain in the short term, they could actually contribute to the long term development of chronic pain.

Mice and morphine

Researchers tested their theory by inflicting a nerve injury upon mice. Some were issued with a five-day course of morphine, while others were left untreated. As they recovered, researchers continually tested the pain thresholds of the mice by repeatedly prodding them with nylon filaments. They found that the mice on morphine took 50% longer to regain their normal pain tolerance levels than their non-treated counterparts.

The ‘two-hit’ hypothesis

Following this finding, the team then issued morphine to a group of mice that hadn’t suffered from any injuries. They found that while pain tolerance levels temporarily dropped, the effect was short-lived. This prompted the authors put forward a ‘two-hit hypothesis’ theory, suggesting that opioids only trigger a long-term increase in pain sensitivity when an initial injury is involved. This supports previous research that a single painful experience activates microglia cells. These release inflammasome messengers which actively increase the sensitivity of pain-receptive nerve cells. Once primed, a second stimulus can send microglia into overdrive, which causes them to churn out excessive inflammasomes. The result, is ongoing chronic pain.

The researchers assert that the administration of morphine acts as a second hit, with study co-author Linda Watkins maintaining that the study reveals “a very ugly side to opioids that had not been recognised before.” While opioids are hugely effective at relieving pain, she warns that prescription narcotic painkillers “can have devastating consequences of making pain worse and longer lasting.”

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