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Morphine Doubles Duration and Severity of Pain

Instead of helping to overcome chronic pain, opioid-based painkillers such as morphine, oxycodone and methadone can more than double the duration of pain and amplify its severity, according to a study published in Proceedings of the National Academy of Sciences ( The study has also discovered how to switch off this pain-amplifying mechanism.

The researchers found that rats with chronic nerve pain treated with morphine for just 5 days experienced pain sensitivity that lasted for up to 2–3 months, more than double the control group.

“What we found is that the opioid painkiller activates spinal immune cells, causing a further inflammatory response. The pain is effectively transitioned to a chronic state, making the pain itself both more severe and longer lasting,” says Dr Peter Grace of The University of Adelaide. “This extended period of chronic pain has followed from just 5 days of treatment with morphine,” he says.

The results are concerning because of the huge number of opioid prescriptions written each year. “Our results add weight to the growing body of science suggesting that treatment with opioids such as morphine may in fact be a contributor to people’s chronic pain,” Grace says.

“Importantly, we’ve also been able to block the two main receptors involved in this immune response, including Toll-like receptor 4 and another one called P2X7R, which have both been separately implicated in chronic pain before. By blocking these receptors, we’re preventing the immune response from kicking in, enabling the painkilling benefits of morphine to be delivered without resulting in further chronic pain,” Grace says.

“Novel drugs are currently in the pipeline. If clinical trials of those drugs are successful it could be another 5 years or so before patients are able to benefit from them.”