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Study Suggests Morphine could Prolong Pain

It’s well-known in the medical world that the drugs often prescribed to treat pain – morphine, oxycodone and other opioids – can actually make patients more sensitive to pain (a side effect called hyperalgesia). But a study published in May in the Proceedings of the National Academy of Sciences[1] found even more evidence of the serious side effects of opioids – especially when prescribed at the onset of pain. The authors discovered that these drugs, when administered after a nerve injury, actually doubled the duration of the pain.

Overview of the Study

 “Pain after disease/damage of the nervous system is predominantly treated with opioids, but without exploration of the long-term consequences,” the study says. So to delve further into these consequences – particularly to test their hypothesis that morphine may contribute to “persistent sensitization,” as they call it – the study’s authors conducted a study on rats whose sciatic nerves (a nerve running down their hind legs) had been painfully constricted.

Ten days after the constriction, the rats were given either saline or morphine for five days. Over the next three months, the rats’ sensitivity to pain was tested.[2] The researchers found that the rats who received saline returned to normal sensitivity levels within about six weeks, while those who had morphine took 12 weeks to recover (in addition to experiencing increased sensitivity overall).  

The data, the authors concluded, showed that not only can morphine amplify pain (hyperalgesia), but it can also seriously prolong it, even after the treatment is stopped. This seems to be due to an inflammatory response taking place in the spinal cord.


There are several limitations to the study. Since the study was undertaken on rats, there is no guarantee that the process works the same way in humans. In addition, the rats were genetically similar – and all male – meaning that the human reaction to morphine may not be so homogeneous (although there is unpublished data that supports the idea that morphine could extend pain even longer for female rats).[3]


Researchers are already working on drugs and methods to intercept and reverse the inflammatory response caused by morphine. In fact, this study also found that by inhibiting the inflammatory responses, they could permanently reset the amplified pain to normal levels. This could prove useful down the road in making opioids more effective – thus requiring lower doses and lessening the chances of overdose. 

However, for the time being, this study reinforces the already strong indication that opioids should be prescribed with caution. Their large number of serious side effects, paired with the lack of evidence showing any long-term benefit,[4] suggests the need for other treatments to deal with pain. Minimally invasive procedures or complementary treatments – like physical therapy or behavioral health – may help to fill this gap.


[1] Grace, Peter M., Keith A. Strand, Erika L. Galer, Daniel J. Urban, Xiaohui Wang, Michael V. Baratta, Timothy J. Fabisiak, Nathan D. Anderson, Kejun Cheng, Lisa I. Greene, Debra Berkelhammer, Yingning Zhang, Amanda L. Ellis, Hang Hubert Yin, Serge Campeau, Kenner C. Rice, Bryan L. Roth, Steven F. Maier, and Linda R. Watkins. “Morphine Paradoxically Prolongs Neuropathic Pain in Rats by Amplifying Spinal NLRP3 Inflammasome Activation.” Proceedings of the National Academy of Sciences 113, no. 24 (May 2016).

[2] Servick, Kelly. “Why Taking Morphine, Oxycodone Can Sometimes Make Pain Worse.” American Association for the Advancement of Science. May 30, 2016. Accessed July 19, 2016. http://www.sciencemag.org/news/2016/05/why-taking-morphine-oxycodone-can-sometimes-make-pain-worse.

[3] Sanders, Laura. “Morphine May Make Pain Last Longer.” Science News. May 30, 2016. Accessed July 19, 2016. https://www.sciencenews.org/article/morphine-may-make-pain-last-longer.

[4] Dowell, Deborah, Tamara M. Haegerich, and Roger Chou. “CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016.” Morbidity and Mortality Weekly Report (MMWR) 65, no. 1 (March 18, 2016): 1-49.