Regular Codeine Use May Cause More Pain

People who take large and frequent doses of codeine to relieve pain may actually increase their sensitivity to pain, according to Australian researchers.

Researchers at the University of Adelaide conducted what is believed to be the first experimental study comparing the pain relieving and pain worsening effects of both codeine and morphine.


Codeine has been widely used for pain relief for over 100 years, but its effectiveness has not been tested in this way before. Codeine is cheaper than triptans, and many patients use it to manage migraines and cluster headaches.

“In the clinical setting, patients have complained that their headaches became worse after using regular codeine, not better,” said Professor Paul Rolan, who is also a headache specialist at Royal Adelaide Hospital.

“Codeine use is not controlled in the same way as morphine, and as it is the most widely used strong pain reliever medication in the world, we thought it was about time we looked into how effective it really is.”

In laboratory studies on mice, researchers found that codeine provided much less pain relief than morphine, but resulted in the same level of hyperglasia (an increased sensitivity to pain) and allodynia (a painful response to a normally innocuous stimulus).

“Pain sensitivity is a major issue for users of opioid drugs because the more you take, the more the drug can increase your sensitivity to pain, so you may never quite get the level of relief you need. In the long term it has the effect of worsening the problem rather than making it better. We think that this is a particular problem in headache patients, who seem more sensitive to this effect,” said Jacinta Johnson, a doctoral candidate at the University of Adelaide, who presented her research at the 2013 International Headache Congress in Boston.

Johnson’s work is featured in this month’s issue of Neurology Reviews.

“Both codeine and morphine are opioids but codeine is a kind of ‘Trojan horse’ drug – 10% of it is converted to morphine, which is how it helps to provide pain relief. However, despite not offering the same level of pain relief, we found that codeine increased pain sensitivity just as much as morphine,” Johnson says.

The findings suggest a potential problem for anyone suffering from chronic pain who uses codeine regularly.

“People who take codeine every now and then should have nothing to worry about, but heavy and ongoing codeine use could be detrimental for those patients who have chronic pain and headache,” says Professor Rolan says.

“This can be a very difficult issue for many people experiencing pain, and it creates difficulties for clinicians who are trying to find strategies to improve people’s pain.”

A clinical trial testing a new approach to treating codeine-related headache is now underway at the University of Adelaide.

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