Jan 9 • Sean Overin

A Big Shift in Pain Science?

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In medical education, it is often repeated the old line attributed to Dr. Sydney Burwell:

“Half of what we teach you is wrong and half of it is right — the problem is we don’t know which half is which.”

The 2025 Brain paper, “Adieu to an aphorism: why nociception is necessary for pain,” might be a perfect example of that principle in action. An aphorism is a short, memorable statement treated as a universal truth — and for years, one of the most widespread teaching lines in modern pain science has been:

“Nociception is neither necessary nor sufficient for pain.”

This paper takes direct aim at that claim. The authors agree that the “not sufficient” part still stands, but they make a compelling case that the “not necessary” part doesn’t hold up when you look at the broader neurobiology and the actual evidence.

If they’re right, I think that is an important recalibration, not a rejection of modern pain science, but a refinement. A reminder that even our most trusted teaching lines deserve to be re-examined. 

This hits close to home for me. I’ve had enough personal experience with pain — and with treatments that directly target the biology behind it — to know this conversation matters. I’ll share more on that in a moment… but it’s part of why this paper grabbed my attention. 

And all this to say, we might be nearing one of those moments where we discover which “50%” needs updating — and why that update actually matters in real life. I will share how this paper updates my thinking and approach to pain at the end.
For years, pain educators (including me) have said:
“You can have pain without nociception.”
“Pain is an output of the brain; it doesn’t require a nociceptive signal.”
“Pain is a perception designed to protect you.”

Those ideas come from good intentions: reducing fear, separating pain from tissue damage, and working to truly validate people with persistent pain.

But this paper argues that the pendulum may have swung too far away from the biology. And I agree, in some circles, this is most definitely the case. 

To understand their argument, two definitions matter:

What is nociception?

In classical terms:
Nociception is the neural process of encoding noxious (potentially harmful) stimuli.

But importantly: it is not limited to peripheral nociceptor firing.

For years, pain educators (including me) have said:
“You can have pain without nociception.”
“Pain is an output of the brain; it doesn’t require a nociceptive signal.”
“Pain is a perception designed to protect you.”

Those ideas come from good intentions: reducing fear, separating pain from tissue damage, and working to truly validate people with persistent pain.

But this paper argues that the pendulum may have swung too far away from the biology. And I agree, in some circles, this is most definitely the case. 

To understand their argument, two definitions matter:

What is nociception?

In classical terms:
Nociception is the neural process of encoding noxious (potentially harmful) stimuli.

But importantly: it is not limited to peripheral nociceptor firing.

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What is the nociceptive apparatus?
The authors argue that nociception is best understood as a distributed, multi-level biological system, including:

  • Peripheral nociceptors (Aδ and C fibres)
  • The dorsal root ganglion
  • The dorsal horn
  • Brainstem nuclei
  • Thalamo-cortical networks
  • Limbic circuits
  • Neuroimmune interactions (microglia, astrocytes, immune mediators)

In other words:

Nociception = any activation of the pain-protection system anywhere along this network.

You can have nociception without tissue damage, without injury, and without conscious awareness.

But, as the authors argue, you cannot have pain without some activation somewhere in this system.

That’s the claim these authors are making. 
Let's go a bit deeper ...

Here’s what the authors argue:

a) Nociception is necessary for pain
Not necessarily tissue damage.
Not necessarily a peripheral trigger.
But some activation of the nociceptive apparatus must occur.

b) The classic examples of “pain without nociception” don’t hold up
They review every supposedly canonical case:

  • Phantom limb pain — strong evidence of ongoing peripheral activity after amputation.
  • Congenital limb absence + phantom limb pain — extremely rare, poorly documented, usually interconnected with other nociceptive experiences.
  • Rubber Hand Illusion — heavily confounded; not evidence of true pain without nociception.
  • Thermal Grill Illusion — now thought to activate the nociceptive system at spinal and supraspinal levels.
  • Nocebo & psychologically induced pain — cannot confirm a complete absence of biological nociceptive activity; stress and threat alone can activate the nociceptive apparatus.
  • Allodynia — reflects a sensitized nociceptive system, not an absence of nociception.
  • Brain stimulation / imaging data — shows correlates, not a non-nociceptive route to pain.

Their conclusion:

There is currently no solid empirical evidence of pain occurring in the absence of nociception.

And that challenges a big swath of pain education.

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🧭 A respectful but clear challenge to the roots of pain neuroscience education

This paper directly challenges several long-standing claims from the modern pain education movement, particularly:
  • The idea that pain is a brain-created protective output
  • The repeated teaching that nociception is “neither necessary nor sufficient”
  • The “pain can occur in the complete absence of nociceptive input” storyThe use of illusions (RHI, TGI) as proof of brain-generated pain without biological signaling
  • Some nocebo experiments that were interpreted as “pain from thoughts alone”

Many of these challenges fall onto some of what I have learned through the NOI Group, Lorimer Moseley, and Tasha Stanton. They have and continue to do enormous good in this space by:

  • Reducing fear
  • Popularizing biopsychosocial thinking
  • Helping clinicians move beyond biomedical reductionism
  • Pain advocacy work
  • and so much more...

But some of the teaching narratives built on illusions, analogies, and hypotheses, is not always on solid replicated biological evidence.

This paper argues that:

  • Those examples do not demonstrate pain without nociception
  • They may conflate threat, fear, and expectation with pain
  • “Brain-only pain” is not biologically plausible
  • The nociceptive system can be activated without tissue damage, without obvious peripheral drivers, or without clear conscious sensation — meaning nociception may still be present even when we think it isn’t

So...the field may need to move from “pain, nervous system or brain output” toward

“Pain as an experience that always arises from the nociceptive apparatus — a distributed neuroimmune network — and is shaped by psychological and social context.”

This keeps the biopsychosocial model intact but roots it more deeply in biology.
Why This Matters for Future Pain Treatments

One important implication of this paper is this:

If nociception is always involved in pain — even when tissues look normal — then the entire nociceptive apparatus becomes a legitimate biological treatment target.

This reframes chronic pain research in a way the old aphorism could not.

Under the “pain without nociception” narrative, many biological avenues were seen as potential dead ends because there was supposedly no biological signal to treat.

But if pain always involves:
  • altered ion channels
  • peripheral or DRG excitability
  • dorsal horn sensitization
  • brainstem modulation changes
  • thalamo-cortical dysrhythmias
  • microglial or immune activation

…then the path opens for much more precise biological interventions:
  • glial-targeting meds
  • immunomodulators
  • ion-channel therapies (Nav1.7, TRPV1, ASICs)
  • DRG or peripheral nerve neuromodulation
  • metabolic and mitochondrial support

This model doesn’t make pain “just biology.” It’s simply saying that biology is always part of the picture — even when it’s quiet, subtle, or happening behind the scenes.

And if biology is in the picture, that means we can support it, treat it, or calm it down. I get 3–4 migraines a month, and Sumatriptan wipes them out reliably. It works because migraines have very specific biological pathways: the trigeminal nerve becomes overactive, inflammatory neuropeptides like CGRP get released, and the blood vessels around the brain dilate and irritate pain-sensitive tissues. Sumatriptan directly targets that biology — it activates 5-HT1B/1D serotonin receptors, which shut down trigeminal nerve firing, stop CGRP release, and re-constrict those dilated vessels. 

When the biology causing the pain is targeted, the pain stops. That’s why having clear biological mechanisms could matter more than we think.
📄 Paper: Adieu to an Aphorism: Why Nociception Is Necessary for Pain — published in Brain, 2025. Here. This paper challenges the long-held claim that nociception is “not necessary” for pain, arguing instead that current neurobiological evidence shows nociceptive input plays an essential role in generating pain across contexts.

🎧 Podcast: 227. Questioning Pain Science w/ Asaf Weisman — from E3 Rehab Podcast. Here. Great interview with one of the authors of the paper. 

📄 Paper: A brand-new study (n = 17,200) found that people with a high Systemic Immune-Inflammatory Index (SII) — a simple score calculated from a standard CBC — were 66% more likely to have low back pain. And the effect was strongest in younger adults (ages 20–40), where high inflammation actually doubled the risk of back pain.

Why does this matter?

Because it’s another reminder that back pain isn’t just biomechanics or posture or lifting technique — systemic inflammation is a real biological contributor, and it’s measurable. SII integrates neutrophils, lymphocytes, and platelets to give a snapshot of whole-body inflammatory load.

So if you’re someone with persistent back pain, it might be worth talking with your clinician about whether systemic inflammation could be part of your picture — and whether lifestyle, sleep, diet, stress, movement, or medical strategies that reduce inflammation could make a meaningful difference.

Small changes that lower inflammation can shift pain outcomes more than most people realize.

“Pain may be seen as a sensation that emerged with nociception.”

What the authors are getting at is this:
  • Nociception evolved first. Long before animals had any conscious experience of pain, they had basic neural circuits that detected tissue threat and triggered protective reflexes.
  • Pain evolved later. As nervous systems became more complex, the brain developed a conscious experience — pain — built on top of nociceptive signaling to help guide learning, memory, and longer-term protective behaviour.
  • Chronic pain reflects this same protective system overshooting. The nervous system continues to produce the experience of pain even when tissue threat is low, intermittent, or no longer biologically useful — influenced by everything from inflammation and sleep to stress, beliefs, and social context.
  • This perspective strengthens the biopsychosocial model. It grounds pain in biology (nociception as the foundational input), while fully acknowledging that psychological and social factors can amplify, dampen, or prolong the system’s output.


Take-away:
Pain is not “just in the brain” and it’s not “just in the tissues.” It’s a conscious protective experience that evolved from nociceptive biology, and in chronic states that same system can become dysregulated — shaped by biological, psychological, and social forces. Understanding nociception as foundational doesn't weaken the biopsychosocial model; it actually gives it firmer footing.
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If this paper is right, pain science isn’t being overturned — it’s being clarified. And that refinement matters, because it may point us toward better treatments, more accurate explanations, and a more mature way of thinking about pain. It’s also how we evolve as healthcare practitioners.

Nothing foundational changes:
  • Pain ≠ damage
  • Beliefs, emotions, and context shape pain
  • People with chronic pain suffer enormously
  • Imaging and tissue findings can’t explain persistent pain on their own

But the biology sharpens:
every pain experience involves the nociceptive apparatus — a distributed neural and immune system that can be activated, sensitized, quieted, or stabilized.

Here’s how that changes my practice:

It prompts me to look more closely at biological contributors for some people in pain — inflammation, sleep disruption, immune activity, peripheral generators, migraine pathways, sensitized nerves — not as “old biomechanics,” but as meaningful targets alongside psychological and social factors. It pushes me to refine my assessments, ask better questions, consider updated bloodwork, and explore targeted biological treatments when appropriate, rather than relying on oversimplified narratives that don’t serve patients.

It also invites a more compassionate, precise, and honest approach to care — one that acknowledges the many layers that create pain and the many pathways we have to help. And it nudges me to reflect on my own toolkit: where I’m strong, where I need to grow, and when a patient may be better served through collaboration.

Because the truth is, we won’t be able to help everyone — not fully, not perfectly, not every time. But by updating our understanding, refining our assessments, expanding our toolkit, and working together, we give each person the best chance of meaningful improvement.

Maybe that’s what this refinement in pain science ultimately offers: a clearer map, a humbler stance, and a more effective way forward.

Stay nerdy, 

Sean Overin, PT