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 says the results, published in the journal Proceedings of the National Academy of Sciences (PNAS), further question 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,” Grace says.
“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,” Grace says.
The study was led by Professor Linda Watkins at the University of Colorado Boulder.
Chronic pain affects 10% of the world’s population, about 60 million people, with estimates of closer to 20–25% in some countries.
Grace, who is also a research assistant professor with the University of Colorado Boulder, says the study has 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,” Grace says.
“It means we need a more sophisticated approach.”
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,” Grace says.
“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 chronic pain sufferers could take opiate-based medicine as well as the receptor-blocking drugs 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.
Grace says the team would like to further investigate how broad the receptor-blocking drug is and whether it has similar effects for other opiate-based drugs such as oxycodone and fentanyl, and for other types of chronic pain including low back pain.
– Alannah James