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Does a stubbed toe leave you swearing, yowling and hopping up and down, or do you stoically grit your teeth and move on with your day?

We all tolerate pain differently, whether it’s short-lived or persistent. But for those living with chronic pain, which lasts beyond an injury’s expected healing time, getting a diagnosis is a significant problem.

Chronic pain is complex and often has non-specific symptoms. Sometimes it’s an indicator of a disease such as fibromyalgia; in others, it materialises in the absence of a clear underlying condition. It’s no surprise, then, that most people with chronic pain must see multiple clinicians before they’re diagnosed.

To help patients access the effective treatments at the right time, researchers at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) have partnered with US collaborators. They’re running trials to hone technology that objectively tells a clinician how much and what type of pain an individual is feeling — using a simple blood test.

‘Peripheral blood is a new way to see what’s happening in the brain and spinal cord without actually looking directly at the brain and spinal cord,’ says Prof Mark Hutchinson, leader of the Neuroimmunopharmacology lab at the University of Adelaide and CNBP director.

Links between body and mind

When a person feels pain, their perception of discomfort isn’t simply a matter of a few brain cells firing. It’s a wide physiological reaction.

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Their immune system springs into gear to protect the body against the perceived threat, even if there is no danger. That response, which includes the production of molecules such as inflammatory cytokines, varies depending on the location and severity of the pain in the central nervous system.

To measure these molecular differences, CNBP researchers and their colleagues abroad enlisted the help of hyperspectral imaging. This technology bathes blood samples in light — hundreds or thousands of different wavelengths — then measures what bounces back.

As different blood components reflect different colours, blood from a person who suffers migraines, which has a unique cocktail of pain-related cells and molecules, will reflect a different hue to blood from, say, a fibromyalgia patient.

A world of pain trials

Prof Hutchinson and colleagues are working through a series of hyperspectral imaging trials, with US collaborators, to characterise the ‘colour’ of chronic pain conditions. Some they’ve finished: in early 2020, they completed a study with a large pharmaceutical company to analyse people with migraine. That manuscript is currently under review.

In progress is a study examining the world’s leading cause of disability — chronic low back pain. University of Colorado and Dartmouth University researchers, interested in how cognitive behavioural therapy affected a patient’s pain experience, also collected blood from their subjects. These samples were sent to Prof Hutchinson and his team for hyperspectral analysis.

The trials are also examining conditions traditionally dismissed or overlooked by pain researchers. Take chronic pelvic pain. It can be a sign of diseases such as endometriosis or irritable bowel syndrome, and affects more women than men — up to 1 in 5 and 1 in 12, respectively.

Yet despite being one of the most common medical problems in women, diagnoses are not forthcoming. ‘A woman with pelvic pain usually has to see 4 to 6 clinicians before they receive a diagnosis,’ Prof Hutchinson says.

But there are biomarkers linked to pelvic pain. Prof Hutchinson co-authored a study, published in the Journal of Pain Research in March 2020, which showed women with painful periods — also called dysmenorrhea — produced more than twice the amount of a cytokine called interleukin 1 beta than healthy counterparts. 

‘The immune response was changing relative to not only the pain state, but also the type of recovery that the women had,’ Prof Hutchinson says. And in as-yet-unpublished work, he and colleagues differentiated women with pelvic pain using hyperspectral imaging.

Also underway is a trial of chronic pain associated with sickle cell disease, a group of inherited blood disorders that leave a patient with rigid, sickle-shaped red blood cells instead of soft spheres.

Patients experience intense pain when their hard, misshapen red blood cells become stuck in small blood vessels and block circulation. While that pain may come and go during a patient’s early years, it becomes chronic with age.

So partnering with the Detroit Medical Centre — which houses the Sickle Cell Center at the Children’s Hospital of Michigan — Prof Hutchinson’s team is analysing blood from around 70 children with sickle cell disease.

With precise pain phenotyping comes better pain management

Along with providing clinicians and patients with a quick and easy measure of pain, Prof Hutchinson says that hyperspectral imaging could also help sort patients into more specific disease subgroups, which can then help direct them to the most effective therapy.

‘This is another program within the group: if we can make a diagnosis, can we make a precision medicine selection to optimise the first treatment of choice?

For instance, when triptans emerged as migraine relief in the 1990s, clinicians soon realised that the drugs worked for some patients but not at all in others. Today, people with migraine are sorted into triptan responders and triptan non-responders, and Prof Hutchinson believes these groups can be broken down into smaller subcategories, based on their blood make-up.

‘There may be a signal that’s in the diagnostic power of the existing test which says, based on your blood test, you’re more likely to respond to drug A than drug B,’ he says.

‘And now we’re really pushing to the direction of precision medicine’ — offering tailored pain treatment regimens on a patient-by-patient basis — ‘and this is where it gets exciting.’