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Newcastle-based research into chronic pain is examining signals between the spinal cord and brain, with the aim of developing better drugs and treatment methods.
Scientists say pain is a massive problem that needs fresh solutions, given the failings of opioids and other drugs and treatments used for pain.
One in five Australians will experience chronic pain in their lifetime.
University of Newcastle Associate Professor Brett Graham will speak at a free HMRI community seminar on Wednesday night titled, "Finding the Pain Switch".
His research involves studying the nerve cells and circuits in the spinal cord and "how they deal with pain signals".
"You can consider that as the gateway to the brain."
These signals are not yet pain because "we only experience it as pain if it gets to the brain".
When people get injured, the spinal cord receives "a barrage of signals" that can "provoke changes and alterations that set up a pain generator, if you like".
"Essentially the spinal cord can maladapt and be one of the culprits in generating chronic pain," he said.
"We all feel normal pain - you can almost think of it as healthy pain.
"You need pain, it's a danger signal that tells you there's something wrong with some part of the body and if you don't respond to that you're in big trouble.
"We're not trying to eliminate that pain."
The problem is acute pain can turn to chronic pain and "become established in the nervous system".
This can occur even though the injury has healed or the stimulus or danger has gone. So the pain pathway from the spinal cord to the brain can become altered.
"Now it's hypersensitised or capable of generating signals without that danger signal," he said.
A/Prof Graham is working on the fine details of how this occurs in an effort to improve treatment.
He works to pinpoint the nerve cells involved in signalling pain, with the aim of developing better treatments.
Doctors have traditionally prescribed pharmaceutical opioid painkillers as a treatment for chronic pain.
But these drugs are addictive and can lead to more problems. People develop tolerance to them.
"So the drugs lose their impact and you have to take more. You have these escalating doses just to get the same amount of relief."
This problem has led to the opioid epidemic in the United States, in which about 500,000 people have died from overdose in the past 20 years.
"It's a massive problem in Australia, too," A/Prof Graham said.
In 2020, there were almost 1100 opioid deaths in Australia.
Medical practice guidelines have now changed and opioids are no longer recommended as a first-line treatment for chronic pain.
"The first-line medications for many pain conditions are actually antidepressants, things that work on mood rather than pain," he said.
"They're not really even pain drugs. But we're left having to use them, which can take the edge off and modify how we experience pain and improve quality of life, but they come with side effects."
This highlights the lack of medical tools available to treat the underlying dysfunction that causes chronic pain.
An example of such dysfunction is a "sensory deficit" in which even touch can cause pain. People can also suffer bouts of spontaneous pain "without any evidence of where it's coming from".
This is why researchers like A/Prof Graham are embracing precision medicine to seek better, more targeted treatments.
"Even the best pain medications can be thought of as like throwing a blanket over the whole region, trying to shut everything down.
"You might have some success, but there are all these off-target unintended consequences and side effects."
A/Prof Graham is working with clinicians in the field, who are treating people with pain conditions.
"That's one of the important elements of what we have at HMRI now, with the Brain Neuromodulation Research Program," he said.
Associate Professor Marc Russo, a pain clinician, will also speak at the forum.
He will provide an overview of various pain therapies, including the use of neuromodulation therapies.
Another side of pain is the people who sometimes don't feel it. There are many cases of people getting a bad injury playing sport or on the battlefield, for example, and not feeling the pain or barely feeling it. Endogenous systems in the brain and body can "shut the gate on the transmission of pain to the brain", A/Prof Graham said.
"And brain circuits can redivert your attention and dial down your pain experience."
These same systems can become dysfunctional. So instead of suppressing pain, they can "stir up the spinal cord" and create an "exaggerated experience".
A/Prof Graham said links between the body and mind are "part of the pain picture".
Chronic pain is linked to "multiple combinations of parts of the nervous system that become dysfunctional".
He said it is a complex problem, but scientific advances are making progress and offering people hope.