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It’s one of our most primal sensations, but despite its many flavours and nuances, ‘pain’ is often used as a broad catch-all term. So how is pain defined, really, and how can we improve pain relief?

There are two main pain categories. You’re probably most familiar with nociceptive pain; discomfort triggered by an injury or inflammation. Then there’s neuropathic pain, which originates from nerves or neural pathways rather than damaged tissues.

These are not mutually exclusive; people commonly live with a mix of the two.

Pain is also characterised by intensity — usually self-reported on a scale from zero to 10 — and duration: acute, or short-term, and chronic, or persistent, pain.

Acute pain serves an evolutionary purpose. It warns us of a real or perceived threat, like an angry wasp or a hot pan handle. Treatment is generally straightforward — pain-relief medication — and once the wound heals or danger disappears, so too does the pain sensation.

Chronic pain is a more insidious beast. It lingers long after an injury has mended — even if the injury isn’t ‘visible’ such as after a stroke or in diabetes, says Prof Mark Hutchinson, ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) director and leader of the University of Adelaide’s Neuroimmunopharmacology lab.

That’s because chronic pain perception arises from cells in the central nervous system, which — for some reason — are modified around the time of injury. But locating these pain patterns in the brain or spinal cord, and targeting therapies to them, is easier said than done.

To further complicate matters, chronic pain isn’t necessarily a symptom of a disease — it can be a standalone condition. And because no two cases are the same, patients — especially women — usually see multiple clinicians before their chronic pain is recognised, let alone treated. In 2018, 1 in 5 of all GP presentations in Australia involved chronic pain.

Fanning the flames

Microscope image of an opioid receptor. Credit: Varun Sreenivasan

How chronic pain is viewed and managed has changed markedly over the past couple of decades. It was largely dismissed as a condition by doctors until the 1990s and early 2000s, Prof Hutchinson says, when opioids became the treatment du jour.

Opioids such as oxycodone and fentanyl interrupt pain signals to the central nervous system. But they require ever larger doses to achieve previously soothing effects and, paradoxically, eventually prolong and amplify pain.

‘Think of opioids as a fire blanket draped over the flames of pain,’ Prof Hutchinson says. ‘The blanket gradually loses its quelling ability and, in this case, the underside of the blanket is an accelerant, so the fire keeps getting bigger.’

Opioids also activate the brain’s reward circuits, making them incredibly addictive. So while they’re a short-term solution for acute pain, they’re not recommended for the long term.

What does work for chronic pain, then?

The current gold standard treatment, Prof Hutchinson says, is a combination of therapies such as talk therapy and a range of drugs originally designed for other purposes.

‘This means you go to a pain clinic that has a pain specialist, physiotherapist and occupational therapist, a psychologist, nursing staff and probably someone who can help the person get up to speed with any aids they need. This team works in an integrated fashion to address the full mind-body-environment experience of someone with chronic pain.’

Multidisciplinary care has better long-term outcomes for people — not to mention far fewer side effects — but only 1 in 100 people with chronic pain goes down that route.

Why? Patients might turn up to their GP expecting scans or tests, a diagnosis and an analgesic remedy — not a referral to a psychologist and perhaps a prescription for anti-depressants, Prof Hutchinson says.

Then there’s the matter of cost. All those treatment avenues add up.

‘It’s super expensive, but the people who have chronic pain are often out of work. They often have comorbidities with depression and anxiety and other issues like social phobias, which can stop them from accessing services,’ Prof Hutchinson says.

Treatment gets personal

Prof Hutchinson sees a future of treatment that includes identifying pain-generating cells in the brain and spinal cord, and targeting them. Crucial to this is filling gaps in pain research and knowledge.

An objective measure of pain, for instance, would be a massive help on diagnostic and treatment fronts. For children and unconscious people — anyone who can’t express themselves verbally, really — it’s all but impossible to ascertain how much pain they’re in and, thus, how to best treat it.

Even those who can speak aren’t usually too good at objectively communicating how they feel, Prof Hutchinson says: ‘We don’t have language that allows us to systematically explain to others the type, magnitude and location of pain we’re having.’

Gender bias, too, leaves a woman-shaped hole in current research. We now know that women are overrepresented in chronic pain and react to pain medications differently to men. But as with many research realms, pain perception and drug development studies have traditionally centred around male rodents and humans.

‘This meant that, even in the 1990s and 2000s, many women with migraine, pelvic pain and low back pain were poorly diagnosed and dismissed by doctors,’ Prof Hutchinson says. ‘Still today, with pelvic pain, a woman needs to see 4 to 6 clinicians before a diagnosis is made.’

So researchers like Prof Hutchinson will continue to probe the molecular biology of pain — such as interactions with the immune system — and its chronicity. Understanding these fundamental aspects will help develop effective therapies that can encompass physiological, psychological, social and environmental factors, depending on the patient and their circumstances.

And an era of personalised pain treatment that provides relief to everyone — old, young, male, female, human and animal — will become reality.