The future of pain research

Pain is ubiquitous and debilitating, yet how – and why – it persists in some people has scientists stumped.

To help keep humans and animals alike happier and healthier, researchers at the Australian Research Council Centre of Excellence for Nanoscale BioPhotonics (CNBP) are planning studies which they hope will reveal the complex interactions that create and maintain pain.

A primary focus is on chronic or persistent pain, which – despite afflicting millions of Australians – is only recently recognised as a condition, says Prof Mark Hutchinson, CNBP director and head of the University of Adelaide’s Neuroimmunopharmacology lab.

Unlike acute pain, which disappears once an injury heals or threat dissipates, chronic pain lasts months after tissue damage mends. And while pinpointing acute pain’s source can be relatively straightforward – a twisted ankle, perhaps, or a wasp sting – nailing chronic pain’s cause is a much trickier task.

It can be its own condition or part of a disease, and the same illness or injury in two people can have radically different pain outcomes.

Genetics accounts for around half of pain experience and susceptibility to chronic pain. Factors also implicated in variation include age, sex and past and present lived experience.

People with a history of childhood abuse are more likely to develop chronic pain as adults. Life situation at injury, too, can nudge a short-term hurt into long-term agony.

“Clinicians often hear stories like ‘I had financial trouble, I was having an awful day, then I was going to the shops where I slipped and hurt my back and it never got better,’” Prof Hutchinson says.

Definitive diagnostic devices

Today, many clinicians view chronic pain as a real issue, but there is a long way to go – especially for women, Prof Hutchinson says. Researchers have known for decades that women experience more, and more severe, pain than men, yet they usually must see multiple doctors before receiving a diagnosis.

“Ultrasounds and other tests don’t show anything wrong, so a clinician will say ‘sorry, I can’t do much for you,’” he says. “And that’s the cycle.”

Thus, clinicians and patients need a tool that objectively measures chronic pain and identifies the cells responsible for it. This will help not only under-recognised groups, such as women, but also people who can’t communicate how they feel.

Such techniques already exist. Laboratory tests look for biomarkers in blood and functional MRI produces high-resolution scans which show parts of the brain that “light up” with pain.

These methods are – at least for the moment – confined to research. They’re relatively slow – it can be days before biomarker analysis yields results – or, in the case of fMRI, prohibitively expensive for clinics.

“But they’re going to give you a beautiful understanding of changes for defined pathologies, and perhaps for more intensive investigations in drug discovery and trial programmes, where you want to have the gold standard,” Prof Hutchinson says.

With the aim to develop a benchtop device, he and colleagues are trialling technology called hyperspectral imaging.

With a simple finger-prick blood test, it has the potential to quickly and accurately locate chronic pain in the central nervous system, and inform why, on a molecular level, those cells generate that sensation.

Transition to targeted therapies 

With deeper understanding of pain’s nuts and bolts, treatment will also change for the better – something that’s sorely needed. Opioid dependence harms patients and is a burden on the healthcare system.

“We do not treat pain well,” Prof Hutchinson says. “In humans, we fail most of the time. And even the best medicines we give today only work in a fraction of individuals.”

While current best practice treatment is “biopsychosocial” – addressing physical, psychological, social and environmental circumstances – Prof Hutchinson sees an even more highly personalised future for pain management.

Tailored therapies will tackle pain’s root cause – not temporarily hide symptoms.

There are, of course, challenges with personalised medicine. By its very nature, it must take a whole swag of individual factors into account. And as the patient’s pain changes, treatment will need to be amended accordingly.

“If you have thought-based drivers that are enabling the persistence of pain, cognitive-behavioural therapy might be the best option,” Prof Hutchinson says.

“Whereas with neuro-immune pain, you might need a combination therapy which includes medication. Then you need to know: is the pain in the somatosensory cortex? A deeper brain structure? Or at the level of the spinal cord? And how does it change over time?

“We need to change the drugs so we’re getting to the cellular basis of the pain. And that’s the challenge.”

Uncovering sex differences will steer pain treatment too. Most experiments – even today – revolve around male human and rodent subjects. But women experience pain in a fundamentally different way, as Prof Hutchinson’s team showed.

They found glia – cells that act as the brain’s immune system – were crucial to sex differences in pain perception. Drugs that target glia, then, may provide effective pain relief for women.

Commitment to creature comfort

With all this work into pain development, diagnosis and treatment, why not extend it to other animals – especially those we farm for our use? 

Pain in livestock is not an insignificant problem; lameness, for instance, can cause distress and suffering to dairy cows. Farmers, too, take a financial hit. Lame cows produce less milk and need veterinary care.

But as with humans, veterinary medicine has traditionally assumed that an animal administered pain relief will feel better.

“That’s not the case,” Prof Hutchinson says. “A proportion of the animals won’t respond well to pain medicine, but that has not been properly quantified yet.”

Hence, he and colleagues partnered with the farming industry to start biomarker discovery research and explore livestock physiology. How can a veterinarian distinguish chronic from acute pain in a lame dairy cow? And how can they deliver a quick, cheap intervention that ensures the cow lives a pain-free and more productive life?

Only by tackling these and other questions will clinicians and patients – and society as a whole – change how they perceive pain, Prof Hutchinson says.

And while pain will always be a part of our existence, such evidence-based research will lay the groundwork for fast and accurate diagnosis and personalised interventions that will start being translated to clinical practice – perhaps as soon as three to five years, he adds.

“There will be a day when there is going to be such a repertoire of technology, biopsychosocial interventions and a few drugs that individuals will regain quality of life to the extent where pain is in the background, but they’re not affected by it.”