Morphine use doubles duration of pain, increases pain severity

Tuesday, 31 May 2016

Instead of helping to overcome chronic pain, morphine can more than double the duration of pain, as well as amplifying its severity, according to new international research involving the University of Adelaide.

The results, published today in the journal Proceedings of the National Academy of Sciences (PNAS), further call into question the use of opioid-based painkillers and treatments such as morphine, oxycodone and methadone.

But there's good news: the research team has also discovered how to switch off this pain-amplifying mechanism, offering some potential hope for millions of pain sufferers world wide.

Studies led by and conducted at the University of Colorado Boulder in the United States found that rats with chronic nerve pain treated with morphine for just five days experienced prolonged pain sensitivity. This lasted for up to two-to-three months – more than double that experienced in 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 study author Dr Peter Grace, Research Assistant Professor with the University of Colorado Boulder, and Research Associate in Pharmacology at the University of Adelaide's School of Medicine.

"This extended period of chronic pain has followed from just five days of treatment with morphine, which in itself is very significant," he says.

Dr Grace says the results are of concern because of the huge number of opioid prescriptions being written for patients 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," he says.

Thanks to the use of a new technology known as DREADD (Designer Receptor Exclusively Activated by Designer Drugs), the researchers were able to isolate the spinal immune cells and prove their involvement in this response to opioid use.

"Importantly, we've also been able to block the two main receptors involved in this immune response, including Toll-Like receptor 4 (TLR4) 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," Dr Grace says.

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

The study, led by Professor Linda Watkins at the University of Colorado Boulder, involved collaborators from the US, China and Australia.

The research has been funded by the National Health and Medical Research Institute (NHMRC) in Australia, the American Pain Society, the National Natural Science Foundation in China, the National Institute on Drug Abuse, National Institute of Dental and Craniofacial Research, and National Institute of Alcohol Abuse and Alcoholism.

The full paper can be viewed online here.

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