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04 Jul 2016
By Alannah James, The Lead South Australia
Morphine can more than double the duration of pain and amplify its severity in the long term, according
to new international research on its effects as a painkiller.
But the study team, which included researchers from Colorado, South Australia and China, has also discovered how
to switch off this pain-amplifying mechanism, offering hope for millions of pain sufferers world wide.
Author of the study and University of Adelaide Research Associate Dr Peter Grace said the results, published in the
journal Proceedings of the National Academy of Sciences (PNAS) , further questioned the use of opioid-based
painkillers and treatments.
“Prior studies have looked at the effect morphine has on pain sensitivity short term, but in this study we looked at the
weeks and months after morphine use,” Dr Grace said.
“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.”
The research team found that rats with chronic nerve pain that had been treated with morphine for just five days
experienced prolonged pain sensitivity than their control group counterparts.
“This extended period of chronic pain has followed from just five days of treatment with morphine, which in itself is
very significant,” Dr Grace said.
The study was led by Professor Linda Watkins at the University of Colorado Boulder.
Chronic pain affects 10 per cent of the world’s population, about 60 million people, with estimates of closer to 20-25
per cent in some countries.
Dr Grace, who is also a Research Assistant Professor with the University of Colorado Boulder, said the study had
huge implications for the treatment of pain worldwide.
“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,” Dr Grace said.
“It means we need a more sophisticated approach because what we found is that opioid pain killers such as
morphine activates spinal immune cells, causing further inflammatory response.”
The research team discovered a way of switching off this pain-amplifying mechanism using a new technology known
as Designer Receptor Exclusively Activated by Designer Drugs (DREADD).
By using DREADD, researchers were able to isolate the spinal immune cells and prove their involvement in this
response to opiate 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 indicated in chronic pain
before,” Dr Grace said.
“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 said chronic pain sufferers could take opiate-based medicine as well as the receptor-blocking drug to
reduce likelihood of long-term effects.
“It means they would need to take two drugs instead of one – they would still be able to use morphine or other
opiate-based drugs as well as the additional drug.”
Novel drugs are currently undergoing testing and are not expected to be on the market for 10 years.
Dr Grace said the team would like to further investigate how broad the receptor-blocking drug was and whether it
had similar effects for other opiate-based drugs such as oxycodone and fentanyl, and for other types of chronic pain
including low back pain.

Published: 04 Jul 2016