Curing chronic pain

University of Adelaide researchers unravel mysteries of the pain puzzle.

A unique partnership between two of the University of Adelaide's senior medical researchers is edging closer to finding new treatments for chronic pain, one of the most common yet little understood conditions.

In a radical departure from accepted medical thinking, Professor Paul Rolan and Dr Mark Hutchinson have combined their different specialist skills to prove a link between pain and the brain's immune system.

"It's a novel approach - and that usually means it's either crackpot or groundbreaking," said Professor Rolan.

"But we're being viewed less and less as renegades because our research is strongly indicating that it's the latter. Over the past four years we've had very few blind alleys."

Their work could eventually result in blood tests for the cause of chronic pain and new treatment regimes for thousands of Australians and millions worldwide who suffer from the debilitating condition.

Chronic pain is the fourth most prevalent health issue in Australia and has the single biggest societal impact.

"It is so common that it's embarrassing how little we do actually know about it," Professor Rolan said.

The path to a new approach began in 2008 after Dr Hutchinson, an award-winning pharmacology scientist, returned from the US where he had been exploring the effect of pain-relieving drugs, such as morphine and codeine, on immune cell function.

He had previously held a "vibrant conversation" with an initially sceptical Professor Rolan on his ideas about the connection between chronic pain and glia - immune cells which support the brain's nervous system.

"All existing drug treatments are neuron-related and target the nerves or wiring of the pain system," said Dr Hutchinson. "But in chronic pain the treatment is hit and miss and there are a high range of side effects.

"Our research demonstrates that the immune system may be the cause and that for patients with the right set of circumstances, pain medication actually makes their condition worse."

Their work provides possible answers to some previously baffling yet common medical conditions - pain in limbs which have been amputated and ongoing pain in injured areas of the body which appear to have fully healed. Conversely, soldiers and some accident victims can suffer horrendous injuries yet feel no pain at all until later.

The partnership between Professor Rolan and Dr Hutchinson has been so effective because of their related but quite different skill sets.

Professor Rolan trained in medicine and then clinical pharmacology at the University of Adelaide before embarking on a career in the pharmaceutical industry in the UK, which included developing a new treatment for headache. Since 2005 he has been Professor of Clinical Pharmacology at the University of Adelaide and a Senior Consultant in the Pain Management Unit at Royal Adelaide Hospital.

After graduating at the University of Adelaide Dr Hutchinson undertook postdoctoral training at the world- renowned Centre for Neuroscience at the University of Colorado. He returned to Adelaide and started his own laboratory - the Neuroimmunopharmacology Lab - in the University of Adelaide's School of Medical Sciences physiology discipline.

"Mark tests our ideas on animals in the laboratory but without there being a clinical way of assessing these findings it's not going to work," said Professor Rolan. "The synergies between the two of us are providing a completely new approach."

With valuable support from their PhD students Professor Rolan and Dr Hutchinson have taken giant strides towards proving their theory that chronic pain is immune- related and the result of a genetic predisposition.

Initial proof was demonstrated in the laboratory by transplanting immune cells between rats. The tests showed that the different pain responses of the rats was also transplanted.

But could this be demonstrated in humans?

The 'eureka' moment occurred when capsaicin - the fiery compound in chillies - was placed under the skin of volunteers. A subtle immune stimulant in the form of endotoxin was then given intravenously and it showed that when the immune system was switched it made the volunteers more sensitive to pain.

Several other exciting and related lines of research are now being pursued by the scientists.

They are looking at a diagnostic blood test to identify people with an over-sensitive immune reaction to pain and are assessing existing medications to see if they can be used to calm the system down.

Teams are also testing the exciting possibility of magnetically rewiring the chronic pain-affected brain - safely and drug-free.

Another breakthrough involves the role of codeine and morphine-like medications which, in chronic headache sufferers, have been shown to actually activate the glia immune system to create more pain.

And women who complain of being more sensitive to pain during their monthly cycle might now have an explanation. An increase in the female hormone oestrogen is believed to be turning on the immune pain cells.

The Rolan and Hutchinson team is thinking big.

"Current treatments are not pain modifying - if you stop taking the pills the pain is still there," said Professor Rolan. "What we want to do is not just treat chronic pain but to prevent and cure it."