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Researchers at the University of Sydney have used human stem cells to make pain-killing neurons that provide lasting relief in mice, without side effects, in a single treatment. The next step is to perform extensive safety tests in rodents and pigs, and then move to human patients suffering chronic pain within the next five years.

If the tests are successful in humans, it could be a major breakthrough in the development of new non-opioid, non-addictive pain management strategies for patients, the researchers said.

鈥淭hanks to funding from the NSW Ministry of Health, we are already moving towards testing in humans,鈥� said , a leader in pain research at the Charles Perkins Centre and the School of Life and Environmental Sciences.

鈥淣erve injury can lead to devastating neuropathic pain and for the majority of patients there are no effective therapies. This breakthrough means for some of these patients, we could make pain-killing transplants from their own cells, and the cells can then reverse the underlying cause of pain.鈥�

New research

Published today in the peer-reviewed journal , the team used human induced pluripotent stem cells (iPSC) derived from bone marrow to make pain-killing cells in the lab, then put them into the spinal cord of mice with serious neuropathic pain. The development of iPSC .

聽鈥淩emarkably, the stem-cell neurons promoted lasting pain relief without side effects,鈥� said. 鈥淚t means transplant therapy could be an effective and long-lasting treatment for neuropathic pain. It is very exciting.鈥�

John Manion, a PhD student and lead author of the paper said: 鈥淏ecause we can pick where we put our pain-killing neurons, we can target only the parts of the body that are in pain. This means our approach can have fewer side effects.鈥�

The stem cells used were derived from adult blood samples.

What is chronic pain?

Chronic pain is defined as persistent pain that continues after the original injury has healed. It comes in two forms: inflammatory pain and neuropathic pain.

This study in mice looked at neuropathic 鈥榩ain鈥�, which occurs after damage to the nervous system and, in humans, is usually described as an electrical or shooting pain.

Neuropathic pain can occur in human conditions such as:

1. sciatica
2. a pinched nerve
3. spinal cord injuries
4. postherpetic neuralgia (shingles)
5. diabetic neuropathy
6. cancer bone pain
7. accidental injuries

Epidemic

Lack of effective treatments for chronic pain has led to an opioid epidemic in the US, where since 2000, around 200,000 Americans have died from prescription opioid overdoses. It is estimated by the that more than two million Americans are currently abusing or dependent on opioids.

鈥淢ost astonishingly, opioids are not even an effective treatment for chronic pain, but clinicians have few other options,鈥� Professor Neely said.

鈥淓xisting treatments for neuropathic pain necessitate long term treatment with repurposed anti-convulsants and anti-depressants. These treatments are not specific for pain and have extensive side effects and importantly, these drugs together seem to really help only around 25 percent of patients.

"Virtually everyone will experience some form of chronic (untreatable) pain at some stage in their lives,鈥� Professor Neely said. 鈥淚n view of this immense and unmet problem, developing new non-opioid, non-addictive, pain management strategies are critical for our ageing society.鈥�

The total financial cost of chronic pain in Australia in 2018

Researching new pain drugs

Professor Neely鈥檚 team work in functional genomics and study chronic pain at the and he heads the Sydney Genome Editing Initiative at the University of Sydney.

The team has completed a whole genome dissection of acute pain, published in Cell, and developed a chronic pain assay in the fruit fly.

The same team found an , published in the prestigious journal Nature Communications, while studying deadly Australian creatures in order to understand what causes pain and what might block pain.

鈥淢ost of our work is directed at developing non-addictive pain killers for humans,鈥� said Professor Neely. 鈥淲e are throwing everything we know at this problem.鈥�

Declaration: This research was funded by the . The next stage of the research is funded by the NSW Ministry of Health