Issues Magazine

Progress in Pain Research

By Michael Vagg

Pain research is beginning to mature, with the promise of new treatments for people living with pain.

Imagine being able to change what you eat to reduce long-term back pain, or to have a brain scan to see how your psychology treatment is progressing. Would you have a gene test before surgery so that you receive the painkillers that suit you best? These scenarios are likely to become part of pain treatment regimes in the next few years.

Since the founding of the International Association for the Study of Pain in 1973, the scientific world has seen an explosion in research activity in pain-related areas. Knowledge has expanded so rapidly that a new medical specialty has formed to disseminate and put to use our understanding of the multidimensional nature of pain as a human experience.

Australia’s Faculty of Pain Medicine (part of the Australia and New Zealand College of Anaesthetists) was the first professional body in the world to achieve specialty recognition by the Australian Medical Council in 2005. New Zealand followed in 2012. Sydney University has established pain management as an academic discipline, and remains the only Australian university to do so. Pain research has taken so long to come of age largely because of the complexity of the brain and spinal cord, and the lack of sophistication of research technology.

It is hard to think of another area of medicine where the lab rats are so far ahead of the patients in the clinic. Gene technologies that enable scientists to remove particular genes from breeds of mice have been incredibly productive. Mice, rats and guinea pigs can be bred to be completely unable to generate a pain signal in their nerves, to be unusually sensitive to developing chronic pain, to get arthritis at a young age or have a huge number of other genetic manipulations.

In one US study, copies of an anti-pain gene, carried by modified viruses injected into the spinal cords of rats, cured severe nerve pain. Studying such animals and their nervous systems continues to generate incredibly valuable insights into how pain works, and to identify targets for treatment.

Rats have also shown us that diets low in polyamines can reduce pain following a nerve injury. Polyamines stimulate receptors that regulate pain signals on their way to the brain. The so-called NMDA receptors, found mainly on spinal cord nerves, amplify pain signals less in rats that are starved of dietary polyamines.

Humans share this pathway, and NMDA receptor-blocking drugs exist. Given that their use is restricted to specialised pain units in big hospitals, a simple dietary intervention is very promising but human trials are only just getting underway. Foods high in polyamines include wheat germ, rice, mango, pumpkin, beef, pork and chicken. Soybeans, mushrooms, and green tea leaves also have high levels.

Some of the most eyebrow-raising findings to date have come from the growth in functional magnetic resonance imaging research. Professor Irene Tracey and her colleagues at Oxford University’s Centre for Functional Magnetic Resonance Imaging of the Brain have used this tool to perform studies that have revolutionised our understanding of how brains with chronic pain operate. They can use the scans to show differing responses to drugs between pain patients and control volunteers, predict some of the scores on tests of coping style, and also demonstrate the degree to which a brain exposed to constant pain for months or years undergoes substantial reorganisation.

Tracey’s evidence supports a convincing argument that long-term pain is far more of a degenerative brain disease than anything going on with the body part where the pain is felt.

It appears that some of these changes are reversible: when arthritis patients having knee replacements were scanned again after surgery, their brains had begun reacting to pain more like a normal brain.

Other studies have documented changes in the way that “chronic pain brains” perceive objects and space around them. Quite literally, people with chronic pain see, hear and otherwise experience the world differently.

Opioid (morphine-like) drugs have been a mainstay of pain treatment for centuries. However, effectiveness, severity of side-effects, speed of metabolism and excretion, and effects on mood vary wildly between individuals.

Research into the influence of genetics on these factors is slowly bearing fruit. We may be just a year or two away from a simple blood test that can generate a pharmacological profile of an individual’s response to opioid drugs.

Replacing the current trial-and-error approach would mean that only effective and tolerable drugs will be chosen if postoperative or longer-term pain treatment is required. Technologies like patch delivery and lozenges to deliver powerful analgesics are already here, and the future may include designer drugs whose delivery and metabolism can be tailored to personal genetic profiles.

Disappointingly, Australia has very little by way of an organised research effort into chronic pain. The National Pain Strategy, published in 2010, calls for a nationally coordinated set of research priorities so that long-term research capabilities can be grown, ensuring that Australians will not miss out on a share of the coming wave of smarter, safer and more potent pain treatments. Although the investment costs may be steep, the massive economic and social toll of undertreated pain makes pain research seem cheap by comparison.

Persistent pain roughly doubles a person’s risk of serious mental health problems and is arguably the leading health-related cause of unemployment for young and middle-aged adults. Surely the humanitarian and economic arguments for supporting pain research are overwhelming.