Detailed guides to painful problems, treatments & more

Pain is Weird

Pain science reveals a volatile, misleading sensation that comes entirely from an overprotective brain, not our tissues

Paul Ingraham • 75m read

Pain is not just a message from injured tissues to be accepted at face value, but a complex experience that can be tuned by your brain — and probably more than you think it can, and for weirder reasons. Chronic pain is as volatile and hard to predict as weather, jostled by countless unknowable systemic variables — but especially the potent perceptual filters of the brain. The results are often counter-intuitive.

The science is clear: the brain makes pain. Pain is 100% Brain Made®, like everything else we perceive.1 Threat signals from “insulted” tissues are only one factor of many that the brain considers before creating an experience of pain. The brain often even over-protectively exaggerates pain, sometimes sounding alarms so persistently false that it can become a much bigger problem than whatever caused the alarm in the first place: “sensitization.”

Does all this brain involvement mean can we think pain away? Just how much power does the mind have over pain? Can confidence and education cure? The long answer is on another page, Mind Over Pain. Here’s the short answer: pain is mostly up to our brains, not our minds, and it’s extremely hard to boss our brains around. There are some opportunities to “hack” the pain system a little, but you have to understand the system, and that’s what this article is for.

Many discoveries about the physiology of pain2 have been painfully slow to reach the public, or even health professionals. This is useful stuff, and it needs to be shared.

The main take-home lesson from weird science of pain is that pain is not a reliable sign of what’s really going on, and we need to stop thinking of it as an automatic, proportionate warning about a tissue damage. We tend to latch onto single sources of pain: “it’s all coming from the _____, I know it!” And there’s a long list of usual suspects, of typical scapegoats for common kinds of pain. But it’s rarely that simple, rarely a single source.3 Chronic pain is usually a witch’s brew of factors, complex by nature (not just unusually bad luck). At the least, pain always has a layer of brain-generated complexity. At the worst, the pain system can malfunction in colourful ways, causing pain that is more intense and “interesting” than just a symptom — sometimes the pain is the problem.


The biology of pain is never really straightforward, even when it appears to be.

“Reconceptualising pain according to modern pain science”, Lorimer Moseley


One of the principle qualities of pain is that it demands an explanation.

Plainwater, by Anne Carson


Perception is the brain’s best guess about what is happening in the outside world. Perception is inference.

Scratching an itch through the scalp to the brain, by Atul Gawande


2 good videos on this topic

This well-produced short video neatly summarizes many of the key points of the content of this article. Great explanation of how pain works! (But their advice about what to do with that knowledge is off-key — more about that in Mind Over Pain › Pain Education › How pain education can go awry.)

Another fine video “summary” of a different sort: this hilarious TED talk about a snake bite and pain neurology. No, really, you will actually laugh! It’s like stand-up comedy. Australia’s Lorimer Moseley, Professor of Clinical Neurosciences and tireless pain researcher, is one of the best public speakers I’ve ever seen — a must-watch for anyone with chronic pain, and the professionals who care for them. Does he say “groovy” just a couple times too many? Maybe! But it is groovy … mate.

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“Pain is an opinion”: Ramachandran’s excellent phrase

Ramachandran said that “pain is an opinion” — which sounds like a flaky New Age mind-over-matter theory. But Ramachandran is no mystic or guru: he is a neurologist and scientist. This passage is mainly known for the first few words, a pithy statement of the modern understanding of how pain works:

Pain is an opinion on the organism’s state of health rather than a mere reflexive response to an injury. There is no direct hotline from pain receptors to ‘pain centers’ in the brain. There is so much interaction between different brain centers, like those concerned with vision and touch, that even the mere visual appearance of an opening fist can actually feed all the way back into the patient’s motor and touch pathways, allowing him to feel the fist opening, thereby killing an illusory pain in a nonexistent hand.

Phantoms in the brain, by VS Ramachandran and Sandra Blakeslee

He then tells the story of an extraordinary cure of a man with phantom limb pain, tortured by agony in a clenched fist that was not there. With a clever arrangement of mirrors, Ramachandran created the illusion that the man’s amputated arm was restored — a sort of “virtual” limb. The mere appearance of his phantom hand opening and closing cured his agonizing “spasms.” He felt better because of the illusion that he was better — because he thought he was better. The mirror-cure of phantom limb pain is quite one of the most peculiar results in all of pain science.

Since then, “mirror therapy” has been studied and applied in many ways. A 2007 study showed that mirrors aren’t actually necessary to achieve this effect.4 Mirror therapy is probably just a “fun” way to visualize healthy movement — which may also work fine without mirrors.5

There are many stories of people who suffer extraordinary tissue damage and surprisingly little pain, like the Belarusian pilot who crashed and was impaled by a tree branch as big as a fence post, but cheerfully greeted his rescuers by saying, “I am Groot!”6 He continued to joke throughout his care (“Can you take this sliver out, doc?”) and was repeatedly photographed smiling and behaving normally.

Such anecdotes are fairly common; people can be freakishly pain tolerant. But what about the opposite? If “pain is an opinion,” then surely sometimes the opinion is excessively negative…

Pain with little or no injury

X-ray image of a foot, with a nail embedded in the distal forefoot. Based on its position, it’s ambiguous whether it has passed between the toes.

Can a nail between the toes actually fool someone into thinking they’ve been impaled? Image courtesy of Andrew Dixon, Radiopedia case 36688. Nail Photoshopped into the image for dramatic effect.

Such stories seem to show that a pain experience can be powerfully modified by the mind, if not conjured out of almost nothing. The best known extreme example was reported in the British Medical Journal in 1995, and has been widely cited:

A builder aged 29 came to the accident and emergency department having jumped down on to a 15 cm nail. As the smallest movement of the nail was painful he was sedated with fentanyl and midazolam. The nail was then pulled out from below. When his boot was removed a miraculous cure appeared to have taken place. Despite entering proximal to the steel toecap the nail had penetrated between the toes: the foot was entirely uninjured.

JP Fisher, senior house officer, DT Hassan, senior registrar, N O’Connor, registrar, accident and emergency department, Leicester Royal Infirmary7

If we accept that story at face value,8 then his pain was a classic “nocebo” — the opposite of a placebo.9 But this is the only widely known or cited example of fear-powered pain.

I know of another anecdote from a professional, about a man who was rescued from agony by learning that his bright red poop was caused not by internal bleeding but… beets! (I tell the whole story below.) Where did all the “agony” come from? Certainly not the beets. It may be hard to distinguish between agony and panic, which is partly the point. This is actually a common example of nocebo in medicine: people eat beets, think there’s blood in the toilet, and call 911. Funny if it’s not you! They don’t all have pain, but some do.

If there are other weird tales of great pain with no apparent cause, they are hard to find. It makes sense that they would be both rare and/or under-reported.11 But they may be the tip of an iceberg of more ordinary cases of pain out of proportion to the injury, which would definitely be under-reported: “injury seemed a lot more painful for the patient than I would have expected” is probably so common that it’s barely worth a story at a dinner party, let alone a formal case report.

There is experimental evidence of pain that is amplified by the mind: for instance, fear of pain makes people more sore for longer after a workout,12 and a bogus pain-enhancing ointment actually made people more sensitive to painful pressure.13

And there are many compelling anecdotes about functional neurological disorders (the fancy way to say “psychosomatic illness”), and “the two most common symptoms are fatigue and pain.”14 (On the other hand, virtually all sources tend to just assume that unexplained pain is psychosomatic.15)

Pain is not in lock-step with damage. And yet that is exactly what nearly everyone assumed for a long, long time. And many professionals, even though they may “know” better, often seem to forget how powerfully pain may be influenced — for better or worse — by perception, context, and meaning.

What is surprising is how malleable pain signals are—how readily the intensity of a pain signal is changed by the sensations, feelings, and thoughts that coincide with the pain. … The brain is not a mindless pain-ometer, simply measuring units of ouchness.

Why Zebras Don’t Get Ulcers, by Robert M Sapolsky, 187, 193

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The perception of the perception of pain in olden times (and not so olden times)

For most of the history of medical science, pain was believed to work more or less the way the French philosopher René Descartes described it: a simple signalling system.

  1. The flesh is wounded. (“It’s just a flesh wound!”)
  2. Nerves send an unambiguous message to the brain about the damage. The intensity of the message is directly proportionate to the severity of the injury.
  3. The brain interprets that message at face value — that is, if the message says, “There’s some bad damage here,” we believe it.

Based on this model, almost everyone still — today, in 2024 — assumes that any message sent to the brain by a certain kind of nerve will always cause pain. Health care professionals everywhere still believe that the nerve is “sending pain,” that the signal is pain — and therefore these nerves are habitually called “pain fibers” and their messages are called “pain messages,” an equivalence between signalling and pain baked right into the language.

All of that is badly wrong. And it’s worse than an understandable oversimplification. It’s really very wrong. In fact, it is now known as the “the naïve view” of pain!16

The labeling of nociceptors as pain fibers was not an admirable simplification, but an unfortunate trivialization under the guise of simplification.

The relationship of perceived pain to afferent nerve impulses, by Patrick Wall and SB McMahon, 254–255

The naive view has been replaced by the neuromatrix

The first dent in that old pain paradigm came in 1965 with gate control,17 which showed that other inputs can pre-empt pain (counterstimulation). That was the first strong evidence that pain isn’t a completely predictable response to noxious stimuli.

Ever since, it has become increasingly clear to pain scientists and neurologists that the simplistic pain-fiber model is hopelessly inaccurate. Even microscopic worms with only two trouble-detecting nerves have context-sensitive pain experiences.18 Even their pain is an “opinion,” an interpreted experience. And of course it makes complete evolutionary sense. Pain is clearly a more useful experience when it is “smarter.”

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What goes up, must come down

Pain is usually less intense when we feel safer. This was demonstrated early in the history of pain research by a famous paper about wounded soldiers in WWII: they experienced surprisingly little pain, despite severe injuries, probably because they were just so glad to be off the battlefield.19 Ever since, researchers have been trying to understand how that actually works, and these days we have a pretty good idea.

The brain is not just a passive, gullible receiver for whatever messages the peripheral nerves send upstairs. And, if you think about it, it’s kind of strange that we would ever have thought of it that way, because this is, after all, the brain we’re talking about: seat of consciousness, the generator of your reality. Brains critically evaluate all the danger messages and put them in context before deciding how seriously to take the situation.

Once a danger message arrives at the brain, it has to answer a very important question: “How dangerous is this really?” In order to respond, the brain draws on every piece of credible information — previous exposure, cultural influences, knowledge, other sensory cues — the list is endless.

Pain really is in the mind, but not in the way you think, Moseley (TheConversation.com)

As if that didn’t complicate things enough, once your brain has made up your mind, it also sends messages downwards that actually affect the function of the peripheral nerves.20 Thus everything that hurts involves a conversation, a sort of debate between the central and peripheral nervous systems. It could be dramatized like this:

NERVES Got problems here! Bad problems! Red alert!
BRAIN Yeah? Hmm. Okay, so noted. But you know what? I have access to information — sorry, it’s classified, you’ll just have to take my word for it — that suggests that we don’t have to worry about this much.
NERVES I’m telling you, this is serious!
BRAIN Nope, I don’t buy it.
NERVES Look, I may not have access to this “information” you’re always talking about, but I know tissue damage, and I am not kidding around, this is a credible threat, and I am going to keep telling you about it.
BRAIN Actually, you’re having trouble remembering what the problem is. You’re going to send me fewer messages for a while. Also, these aren’t the droids you’re looking for.
NERVES Uh, right. What was I saying? Gosh, it seems like just a second ago I had something important to say, and it’s just gone. I’ll get back to you later I guess …

The brain can even boss the nerves around, tell them how sensitive to be. When anxious, the brain might request “more information” from the peripheral nerves, ordering them to produce more signals in response to smaller stimuli. Or it might do exactly the opposite. There is extensive recent evidence that the peripheral nerves can even physically, chemically change, perhaps in response to brain requests, tissue conditions, or both. To extend the analogy, this isn’t just twiddling the volume knob, but changing the equipment, changing the signal before it even gets to the “amplifier.”

(Just for fun, have a look at the complex version of that diagram. SHOW)

In short, messages don’t just go up to the brain, they go down. This two-way functionality in the pain system is the main difference between modern pain science and old-school pain science.

But most of the modulation is probably central: we only feel what our brains allow us to feel. Even “loud” sensory messages can be filtered down to almost nothing by the central nervous system … or, conversely, “quiet” sensory messages can be amplified. The quality and intensity of the final experience is clearly the product of an elaborate set of neurological filters.

Perhaps many patients whom doctors treat as having a nerve injury or a disease have, instead, what might be called sensor syndromes. When your car’s dashboard warning light keeps telling you that there is an engine failure, but the mechanics can’t find anything wrong, the sensor itself may be the problem. This is no less true for human beings. Our sensations of pain, itch, nausea, and fatigue are normally protective. Unmoored from physical reality, however, they can become a nightmare … hundreds of thousands of people in the United States alone suffer from conditions like chronic back pain, fibromyalgia, chronic pelvic pain, tinnitus, temporomandibular joint disorder, or repetitive strain injury, where, typically, no amount of imaging, nerve testing, or surgery manages to uncover an anatomical explanation. Doctors have persisted in treating these conditions as nerve or tissue problems—engine failures, as it were. We get under the hood and remove this, replace that, snip some wires. Yet still the sensor keeps going off.

So we get frustrated. “There’s nothing wrong,” we’ll insist. And, the next thing you know, we’re treating the driver instead of the problem.

Scratching an itch through the scalp to the brain, by Atul Gawande

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So what is the opposite of the “naive” view? A little more technically now

If pain isn’t merely a response to signals from the tissues, what is pain actually a response to? Here’s a slightly more formal and technical explanation….

Pain is the output of a dazzlingly complex threat-detection system that generates pain experiences roughly in proportion to perceived threat, based on all kinds of sensory inputs as well as their meaning and context.

All that input produces the neuromatrix: a distinctive, fingerprint-like pattern of neurological activation determined by genetics, experience (especially trauma), and finally by our immediate situation.21 Disturbances in the neuromatrix produce pain, which might not be triggered by anything obvious or familiar.

You can think of the neuromatrix as a virtual model of your body: if the model hurts, then you hurt.

So the way pain really works is much more complicated, interesting, and in some ways useful than the naive view.

Pain is a complex and multidimensional experience produced by multiple influences.

Ronald Melzack and Joel Katz (2013)

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Nociception versus pain

There is technically no such thing as a “pain signal,” and a nerve should never be called a “pain” nerve. It doesn’t detect “pain.” It only detects some kind of stimulus in the tissue … and the brain decides what to make of it, how to feel about it, and what to do about it, if anything.

So what do they detect, if not pain? Noxious stimuli. And what are those nerves? Nociceptors.

Nociception is the conversion of noxious stimuli into nerve impulses — raw data about possible threats that might lead to an experience of bain, if the brain sees a need… which it routinely doesn’t.

In fact, we are constantly exposed to lots of minor noxious stimuli without pain.

On the other hand, major sources of nociception usually do lead to pain — like from a burn, cut, or stepping on a Lego on your way to the bathroom at 2am.

But not always. And pain can sometimes happen without any nociception at all. Or it might just be out of proportion to it! This is the weirdness that this article is all about, and why the definition of nociception matters to a lot of people with serious pain: it’s a key technical detail about how pain works. The difference between pain and nociception is critical to understanding the weirdness of pain.

For everyone else, it’s mostly splitting hairs, a level of precision we don’t need to use in most communication about pain. Your doctor will probably be puzzled if you say, “I have a pain, but I can’t figure out the source of nociception. Or maybe there isn’t one.”

But knowledge is good. I also don’t need to know as much about wiring as an electrician, but I am still happy to learn whatever I can.

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Part 2

Cool 😎 Examples of Pain Weirdness

Pain science oddities and unusual case studies and anecdotes

We cannot trust our eyes, and we cannot trust our pain. Pain is a lot like these amazing illusions — that is, it is warped by our expectations and point of view:

Unlike these clever models, though, we can’t turn it around to see what’s really going on. And trying to see through the illusion, trying to believe that there’s nothing much actually wrong with our tissues (often true), is even more difficult than seeing through these illusions. But that challenge is what recovery is all about: trying to change our expectations and point of view with interesting new sensations and movements.

Examples are helpful. Demonstrations that punch through the illusion.

In the sections ahead, we’ll look at interesting scientific studies and clinical cases all showing different perspectives on how the brain modulates pain. In some cases, they also show how it is influenced by our minds, directly or indirectly. For example, being in love influences pain, and being in love is richly psychological — but also infamously uncontrollable.

Romance as a pain-killer

Thanks to a couple quirky studies in 2010 and 2014 study, science has confirmed that being in love relieves pain — a lovely example of the potential power of the mind over pain.2223 Falling head-over-heels is not exactly a convenient solution. As researcher Dr. Sean Mackey put it, “We can’t give you a prescription for love” — not one that’s easy to fill, anyway.

Falling head-over-heels is not exactly a convenient solution, however. As researcher Dr. Sean Mackey put it, “We can’t give you a prescription for love” — not one that’s easy to fill, anyway.

But we can work to give love more of a chance to grow and thrive. You can’t benefit from the pain-killing effect of love if you aren’t in love, and there are obviously ways to improve your chances of getting there.

Closely related: pain is also muted when romantic partners hold hands.24 Aw.💕

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Weird illusions! Shrinking pain with de-magnification

Cartoonish illustration of a magnifying glass looking at a swollen, red thumb.

If you view a painful hand through a magnifying glass, it will actually get more swollen and inflamed — that is, if you make it look bigger, it will feel like a bigger problem.25 And the reverse is true too! Use optics to make it look smaller, and swelling will go down. Incredible, right? Jedi pain tricks! But … do you have a de-magnifying glass handy? Where do you buy even one of those, let alone a big one? (They really are hard to find. How about looking backwards through binoculars? Not a great solution.26) And what happens if the pain isn’t in a place that’s so easy to de-magnify, like your low back?

The de-magnification trick is dang interesting, but it’s obviously not a practical approach to most pain. The effect is real under the right circumstances, but trying to use it as a treatment is like trying to take a magician’s trick home with you.

Maybe someday virtual reality tech will make “visuotactile illusions” like this a lot more accessible and convenient. A nifty proof-of-concept study demonstrated that a couple of other illusions can reduce osteoarthritis pain by up to 40%, at least temporarily.27 So what visual sorcery can kill more pain than any other known treatment for that condition? Two similar illusions, using virtual reality goggles to make it look like the knee was either shrinking or stretching. 😜 Whoaa, duuuuude …

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Not looking! What you can’t see can’t hurt you (as much)

Getting an injection actually hurts less when you don’t watch.28 Out of sight, out of mind: if the brain can’t see the threat, it is less sensitive to it. That’s interesting, and like the magnification/stretching/shrinking experiments, it clearly demonstrates that the brain modulates pain and, in that circumstance, we can modulate it. It’s easy to look away from a needle, but with most chronic pain, what is there to avoid looking at? We usually can’t see the threat.

Although it is technically the brain’s prerogative to ignore painful signals from your tissues, that doesn’t mean that there’s any way we can convince it to do so — if there is a destructive disease process going on, for instance, the brain will usually not ignore those signals! The pain system evolved to report problems, and you can count on it to do so most of the time.

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The broken cat demonstration

This is a photo of three-legged cat Isaac, trying to scratch himself with his missing leg:

Now a little to the left … Photo by Reddit user ElenTheMellon.

That has got to be super frustrating! The pathetic futility of Isaac’s scratching does not stop his brain from trying. Poor little guy! His brain has a picture of how things should be, and he acts accordingly. The impulse is like a freight train, irresistible even when it’s blatantly ineffective.

So it often is with pain: if the brain believes there’s a threat, you’re going to hurt, no matter how pointless it is or how intensely you focus on trying to have more reasonable and rational sensations. It’s mostly just not up to you.

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Pain is the eye of the beholder (literally in this case)

This one’s from my own medical history, in the aftermath of corrective eye surgery in 2011, and some odd consequences shed good light on how pain works: insight from eyesight. Recovery went well initially; a few weeks later, my optometrist couldn’t even find any sign that anything even happened to my left eye. No laser tracks. No remaining signs of recovery. It was ahead of schedule.

But my right eye was a bit blurry, and it ached. In reality, it was also healing on schedule — but it was lagging behind the ahead-of-schedule left, and it was freaking me out a bit. Get a load of what my science-minded optometrist said (paraphrasing) when I told him about this:

People’s eyes often hurt when they think there’s something wrong with them.

That demonstrates that “pain is an opinion” rather well. My optometrist described the following scenario (paraphrasing):

Someone can “discover” an eye problem they’ve had for twenty years and start hurting. They accidentally cover one eye while watching television, happen to notice that the vision in the free eye is a bit off. It’s been off all along — almost everyone is at least a wee bit astigmatic, but the brain completely takes care of that when both eyes are open. But if they notice it with an eye covered, a week later they’re in my office complaining of blurred vision and an ache.

Fascinating. I was paying close attention to my vision in the aftermath of the surgery — probably too close. I “discovered” that the right wasn’t as good as the left, and started checking it even more obsessively. And so it started to ache. And yet it’s only problem was being less awesome than my left. Good grief.

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Pain asymbolia: sensing without suffering, scary scrubbers, and brave mice

Pain is both a sensory and an emotional experience. In general, the suffering is tightly welded to the sensation, so much so that they seem synonymous. To hurt is to dislike hurting. Mostly.29

But what if you could mute the unpleasantness of pain without actually blocking the pain itself? What if you could be conscious of a burn, but not concerned by it? What if it had no effect on your behaviour?

That’s pain asymbolia — pain without meaning — and it’s actually a thing, caused by physical or pathological damage to specific brain structures.30 It’s considered rare, but it could be a spectrum condition, and how would you know if someone just had a bit of it? How would you even know if you were missing just a little of your pain’s meaning? You don’t know how much a pain is supposed to mean to you! And so “it is possible that pain asymbolia occurs more frequently than is currently assumed.”31

Interestingly, it’s also possible that pain isn’t the only thing that loses its emotional meaning; the casualness about pain might only be the most obvious effect of losing “a general capacity to care about their bodily integrity.”32

People with pain asymbolia know they are in pain, but they aren’t fussed about it. If it represents an obvious danger, they are aware of the danger “intellectually,” but they aren’t highly motivated to avoid it. They are not, for instance, spooked by things that have hurt them in the past. Like dish scrubbers…

The scary scrubber teaches me about the motivational power of pain

I was washing dishes with a copper scrubber, and a loose end of copper wire slid several millimetres into the flesh under a fingernail — a tiny freak accident. It felt like a deep bee sting.

Photo of a copper dish scrubber in the bottom of a sink. It has googly eyes, angry eyebrows, and a snarling mouth full of fangs.

This is a much newer, nicer version of the scary scrubber that bit me. The one that bit me was past its best before date, a tangled mess, the wire fragmenting — which is why it had a sharp end to stab me with.

The next day, I found myself weirdly unable to touch that scrubber! The scary scrubber had stung me, and using it with my bare hands felt as repellent as sticking my hand in a blender. Even though it was super unlikely that it would sting me like that ever again, I was extremely motivated not to touch it with my bare hands. And yet a similar scrubby, a steel one in better condition, didn’t trigger the same motivation — my brain, apparently, only perceived scruffy scrubbers as scary!

That’s the motivational power of pain on display — its significance to us, its implications for behaviour — and that’s what would have been missing if I’d had pain asymbolia. If only! I would have been aware of the sting, but the scrubber would not have intimidated me.

That is what pain asymbolia will do for you.

The brave mouse: the unpleasantness of pain relieved

Pain asymbolia was induced in mice in a 2019 experiment by “muting” a brain region.33 😮 Not only does this result stand out for its potential clinical implications, it’s also an important validation of the existence of the phenomenon of pain asymbolia, which has always been a bit of ghostly phenomenon, case studies as rare as Bigfoot sightings and almost as unclear.34

Photo of a dark grey mouse, sitting up a little and eating something with his cute widdle front paws.

You can’t really see it in this photo, but this mouse is a serious badass. She just does not care about pain! Do not mess with her!

When I first came across this study, it seemed really “neat,” but also irrelevant to real patients — cool brain science that is years from helping real people (at best). Plus it’s a mouse study, and the leap from mice to humans is often a deal-breaker, although perhaps less so in this case.35 But after reading Todd Hargrove’s thoughts on it, I am more impressed and optimistic. It could still takes years, of course, but these BLA neurons may actually be Very Important. I’m with Todd; I think the study is:

“…an encouraging sign that reductionist and brain-centric techniques for understanding and controlling pain may be making progress. It’s a welcome change from the all-too common experience of reading papers where the main takeaway is something like ‘wow pain is so complex!’ or ‘we know even less than we thought we knew.’”

But even if it’s not “practical,” it is a vivid demonstration of the complexity of the experience of pain, and how it can — occasionally — be broken into its constituents like a beam of light passing through a prism. It teaches us something quite substantive about how pain works, what it is made of.

Preventing the trauma of chronic pain?

If one stab under the fingernail can turn me into a person that cannot bring himself pick up a dish scrubber, imagine what serious chronic pain can do to a person’s personality. A continuous bombardment of a strong and extremely unpleasant motivation to avoid something they cannot avoid, or often even identify, sounds a lot like literal torture!

People are traumatized and transformed by pain. But that might not happen if the BLA was inhibited — a wild thought.

Induced pain asymbolia could be the best of both worlds: you can still be aware of critical safety information about the world around you, avoiding the disaster of being completely insensitive to pain. But you also avoid the emotional disaster of being traumatized by it!

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Metal rod embedded in arm painless for fifty years

Sensation and pain are nothing if not mercurial. On the one hand, we can be driven half out of our minds by a bit of beef wedged between a couple teeth. Or, stuck right in the other hand, a large piece of metal can be painless for 50 years. Like a turn signal lever.

Art Lampitt got one of those embedded in his arm in a car accident long ago. What with all the other injuries, no one noticed. It didn’t give him any trouble until recently. His arm began to ache and swell and an x-ray revealed a strange, thin third arm bone.

“I was hoping it might be shiny still,” he said in an interview with CBC Radio One’s “As It Happens,” but it was badly corroded — perhaps the reason it finally caused some symptoms, but who knows.

I love medical marvels that challenge our preconceptions about what will hurt. It’s noteworthy that it didn’t hurt for decades — because if that’s possible, just imagine how unpredictable the symptoms of a little arthritis can be — but it’s also noteworthy that it did start to cause trouble eventually. It’s a great example how pain is weird.

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The power of seeing blood

Photo of a bundle of beets.

Beets are the most common source of “blood” in the stool & urine. Photo by Evan-Amos.

This next example is extracted whole from Marni Jackon’s superb book, Pain: The science and culture of why we hurt. This is an amazing anecdote about the power of perception, and what I want to highlight here is that this wasn’t just a case of medical fear and panic: it was a painful experience.

“There are psychic factors involved in every patient’s complaint of pain,” [Bill Livingston] wrote. He tells a story of one midnight emergency to illustrate his point.

A woman called him to report that her husband had just had a “massive bowl hemorrhage and was in a state of collapse.” Just before bed, he had felt some cramping pains and hurried to the bathroom. Then she heard him calling her name, followed by the thud of him falling to the floor. She found him unconscious, white-faced, and covered in sweat. And in the toilet there was a quantity of bright red blood.

Livingston told her not to flush the toilet and rushed over. He found the man lying on the bed, conscious, but in pain. Where does it hurt the worst, Livingston asked. “All over,” the man whispered. He went on groaning as his wife said that he had been in fine spirits and good health, until he had gone to the bathroom.

Livingston examined him, to no avail. Then he went into the bathroom and inspected the alarming-looking contents of the toilet. Beets. Lots of beet fragments. It turned out that her husband had eaten beets for lunch, and little else. Livingston decided that this accounted for the “hemorrhage” and that the man’s state — the pallor, the sweating, and the “all over” pain — had been entirely caused by fright.

The two of them walked back into the bedroom with smiles on their faces, which annoyed the husband, who was languishing on the bed. But when Livingston gave him his diagnosis, the man’s condition improved rapidly. “Within half an hour he was moving about in his usual energetic fashion and offering to pour me a drink if I would stay and chat.”

It hurt all over. Because his brain absolutely believed he was in terrible danger. And no other reason.

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Fear and pessimism predict poor knee surgery outcomes

In the weird world of pain, fearing the worst is at least partially a self-fulfilling prophecy: the more worried you are, the worse things tend to do. There are many examples of this, but this is a good fresh one, and I also like the fact that it’s about something people don’t usually as associate with psychology: knee replacement.

Dr. Gary J Macfarlane, regarding a paper on knee replacement results:

“We identified 3 distinct response trajectories in patients undergoing knee replacement. Expectations of pain/limited function and poor coping strategies differentiated the trajectories, suggesting a role for preoperative psychosocial support in optimizing the clinical outcome.”

Although this evidence doesn’t show it, it also seems reasonable to assume that the reverse is true: if worry is worse, probably hope helps. So anything at all that increases patient optimism and confidence is a good idea.

It’s also a dilemma for health science reporting and clinicians: truth may be harmful! The discouraging reality of side effects, poor outcomes, and other bad science news — and there’s a bunch of bad news about knee replacement, — will make patients more pessimistic and fearful, and therefore will actually causes worse outcomes. But we cannot lie or conceal the truth, either! Awkward. 🎵 The truth may be problematic, but also unavoidable and essential. There is no easy solution to this dilemma.

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Pain as conditioned behaviour

This example of pain weirdness does not have the charming narrative appeal of some of the stories above, like being in agony from mistaking beet juice for blood. It’s abstract, technical, and hypothetical.

But still very cool.

In the beet juice example, we can see a strong element of behaviour in the pain, a complex response to a perceived threat. And behavioural responses to stimuli can be learned. And it’s possible that this is the nature of some chronic pain. What if your brain just kept believing in a threat? What if there was no doctor to reassure you that it’s just beet juice?

Many perceived threats cannot be easily defused and may continue to produce a complex behavioural response that includes pain. In other words, some chronic pain might be a “learned response” to things that shouldn’t hurt: classical conditioning, like Pavlov’s dogs salivating to the ring of a bell. This is a hypothesis. It is plausible enough to be taken seriously, but unproven and strange enough to be rather exotic.

And it gets weirder!

It’s also possible that learned pain can be un-learned. In the fairly well-established neurology of classic conditioning and memory, responses to stimuli are neurologically re-saved every time the stimulus occurs (“reconsolidation”), and that process can be “disrupted.” The hypothetical part is not whether reconsolidation happens or that is can be disrupted (it does, and it can). The question is whether any of that weird neurology is applicable to pain. It might be, but no one knows yet.

Can pain be a “behaviour” in response to stimuli? If so, it can probably be disrupted. That’s the cool hypothesis. That’s the (hypothetical) weirdness.

If so, it’s as much of a “hack” for pain as I can imagine. I discuss this intriguing idea more thoroughly in Chronic Pain as a Conditioned Behaviour.

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Forgetting chronic pain: amnesia as analgesia?

“Forgetting pain” would be an amazing and profound phenomenon… if it actually happens.

Back in 2007, Choi et al. reported two cases of amnesia (different causes) preceding relief from severe chronic pain and the end of any need for opioid management.36 The bizarre and profound implication is that amnesia relieved the pain. 😮

Unfortunately, these stories may not be what they seem, and I cannot take them too seriously.37

But what if amnesia actually did give those people serious relief?

That would suggest that chronic pain is forgettable, and therefore that it was a function of the mind to begin with, something constructed by our brains and therefore dependent on them … to a shocking degree (in these cases, at least). It could mean that pain as a function of identity, of what we think we know about ourselves, implying that this kind of pain cannot persist without context and meaning. It would support the specific premise the authors’ propose: “Nociceptive pain and its emotional component can result in the development of a ‘chronic pain memory’.”

If so, that would not imply that we “control” pain, of course. It would not mean that we can either create or relieve pain with our thoughts, because our “thoughts” are only a small part of what goes on between our ears. We have no more control over what we remember and what it means to us than we have over a phobia or flinching away from a flame.

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The rhythm of throbbing pain

Is your pain a throbbing pain? Pain often has a pulsating quality, especially when it’s severe and acute. If you’ve ever thought about why it pulses, you probably assumed that it’s pulsating with your pulse. Heck, “pulsatile pain” is actually a clinical term used to describe throbbing pain that is assumed to be surging in time with the arterial pulse.

I have always particularly noticed the throbbing of little infections — like a hangnail that’s gotten out of hand — and I always thought that I was feeling the blood pushing through the ultra-sensitized tissue.

But Mirza et al just checked that assumption… and got a fun science surprise. They checked in a bunch of patients with jack-hammering dental pain, getting them to tap out the rhythm of their throbbing with a button… and discovered that their throbs were actually much slower than their heart rates, almost half the pace, just not in sync. They were clearly different rhythms! Not so pulsatile after all.38

That’s a fascinating upset to conventional wisdom.

The authors cannot, of course, definitively explain what does set the rhythm of the throb, but they did take a crack at it: “an emergent property, or perception, whose “pacemaker” lies within the CNS. (Which is a bit of a hand wave. Perception and the brain can explain anything. Try it sometime!)

Reality is always more complicated than the conventional wisdom or a slam-dunk of a debunk. The safe bet is that there are several kinds of throbbing pain. I doubt anyone will be checking them all anytime soon, so we can just enjoy the uncertainty indefinitely. But I definitely suspect that some of our throbbing pains actually are pulsatile. Like that infected hangnail, maybe. Ow, ow, ow, ow, ow…

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Part 3

The Chronic Zone

The dysfunctionality of some persistent pain

Acute pain usually isn't weird. Horrible tissue damage can be surprisingly painless in the right context… but that’s the exception to the rule. Usually it hurts more or less about like you'd expect.

Most of pain’s weirdness happens when you enter … The Chronic Zone.

As pain drags on, its relationship to actual tissue trouble gets sloppier, and in some cases seems to break down completely. Such patients are effectively hallucinating pain, what we might call “false alarm disease.” This phenomenon is broadly known as “sensitization” (but it gets confusing because sensitization is also involved in acute/traumatic pain). The chronification of pain is dominated by the concept of sensitization. It’s probably a big factor in most of the “pure” chronic pain conditions — that is, nasty chronic pain that seems disconnected from any cause, like fibromyalgia, irritable bowel syndrome, or complex regional pain syndrome.

More commonly, chronification of pain involves relatively mild exaggeration of the intensity of ordinary pain problems. This may actually be the much bigger problem for our species. Imagine the tragedy of billions of cases of low back pain, headaches, plantar fasciitis — and many others — that are all 20–60% louder than they really “should” be. Not “false” alarms… just unnecessarily loud.

Sensitization deserves its own article to itself, and it has one: Sensitization in Chronic Pain: Pain itself can change how pain works, resulting in more pain with less provocation. As big as this article is, you can’t really be done learning about how weird pain is until you’ve read that one too. Sorry about that. It’s a big topic!

But here’s a thumbnail sketch. There are three general ways that pain can be worse than it “should” be:

What if the alarm isn’t false? Not all chronic pain is “weird”!

Pain sensation and perception can be badly distorted in various ways, and that is weird and cool and nasty, but also probably quite rare. We probably can make pain up out of thin air, or almost, but we rarely do. And we can have bizarrely painless trauma — like the soldier who barely feels his wound — but we rarely do. All the famous and fascinating examples are famous because they are a bit exotic (and maybe even too “fascinating” to be true).

For most people, most of the time, pain is not weird. It is usually a consistent, predictable, and sensible warning system about tissue danger — just like the “naive view” always assumed. The boring-but-basic reality is that tissue trouble almost always leads directly to pain. Just because that correlation can get messy and break down does not mean that it always does. Pain must be a mostly reliable signal, that’s why it exists (for the same reason reflexes must be).

And another thing: not all chronic pain is dysfunctional. Just because it seems to be dragging on for no good reason doesn’t mean there isn’t actually still a good reason. Sensitization isn’t the only possible explanation for pain that has no other obvious cause.

Much is made of the difference between acute pain and chronic, generally assuming that acute pain is accurate, while chronic pain is exaggerated or outright bogus. But there’s another important possibility: accurate acute pain that just keeps happening, a renewable resource, an ongoing credible threat to tissues that the brain should take seriously.

Some ongoing causes of pain — a thorn, an old wound, a tumour — are almost too obvious to be worthy of mention. But the cause of persistent pain is often baffling because many “thorns” and “old wounds” are largely invisible, and some tumours are really hard to find.39

GO TO TOPCONTENTSNOTES

Two very important types of chronic pain… that don’t even have names to distinguish them

When there’s no clearly diagnosable cause for chronic pain, there are only two possible explanations in principle (aside from outright hypochondria):

  1. either there is tissue insult (a source of nociception) that just can’t be identified (surprisingly common I think), or
  2. the relationship between tissue insult and pain has broken down (also quite common).

And, of course, it could be a blend.

In other words, the alarm of chronic pain might be false, or it could be true, or somewhere in the middle. Sussing out the difference is a huge clinical challenge and another face of pain’s weirdness and complexity.

In this case, the weirdness is just as much about our lack of clearly labelled concepts as it is about the nature of pain itself. There actually isn’t even a term for an ongoing or recurring cause of chronic pain, so I call it “chronic-acute” pain — but that’s just my informal, descriptive term. A more technical description could be persistent nociceptive pain.

Naming it is valuable. The mere existence of chronic-acute pain is an important source of hope and reassurance for many people, because it means that a “thorn” could still be found, and pulled out.

I’m speaking both professionally and personally here. I once had a persistent pain with no apparent cause, and I was told by a series of professionals that my only problem was pure “false alarm.” But then, better late than never, the %#!!$& source was found and removed … and that was the end of my pain. Ta da! My “thorn” was found and removed.

So I suffered a year of serious chronic pain with no apparent source that absolutely was positively, strongly correlated with a tissue insult. My brain was not lying. The alarm was not false. There was just a sneaky reason for it.

GO TO TOPCONTENTSNOTES

Part 4

Can We Think the Pain Away?

I have good news and bad news…


100% of the time, pain is a construct of the brain.

Lorimer Moseley, from his surprisingly funny TED talk, Why Things Hurt 14:33

If that is true — and it really is technically true40 — does that mean can we think brain-built pain away? Can our minds un-build pain? Yes and no, because, as Dr. Moseley explains, “Pain really is in the mind, but not in the way you think.”41 This is a good news, bad news kind of thing. I will get to the good news, but let’s get the bad news out of the way first:

It’s not really possible to think pain away in general. Many wise, calm, confident optimists still have chronic pain.

Pain is a motivator. It exists to get us to act. We hurt when our brains reckon we should do something differently, for safety … but safety is not always possible. The nature of the danger isn’t always clear, or avoidable.

And the brain worries too much: from hangnails to fibromyalgia, it tends to overstate the danger (for rock solid evolutionary reasons), and it can’t be overruled by wishing, force of will, or a carefully cultivated good attitude. The brain powerfully but imperfectly controls how we experience potentially threatening stimuli, but I’m sorry to report that you do not control your brain.

But we do have considerable control over the context in which our brain lives.

We can change our circumstances. We can improve the odds that our brains will become less concerned about our tissues, and lower the volume of the alarm. It’s not mind over pain in the sense of a neurological “hack” or an impressive act of willpower, but it’s not nothing either.

I explore all the various mind-over-pain possibilities in a separate article: Mind Over Pain: Pain can be profoundly warped by the brain, but does that mean we can think the pain away?

Part 5

Advice for Professionals

What are the clinical implications of all this pain weirdness?

It’s not always clear to healthcare professionals how to integrate the weirdness of pain into their work. Physical therapists, massage therapists, chiropractors, and osteopaths in particular — the freelance, “manual” therapists — have generally been barking up a different tree for several decades: looking for the roots of pain in structure and biomechanics, the paradigm of “structuralism.” And structuralism hasn’t been working out all that well.

So what do you do with the information that “pain is an output of the brain”? Knowing that pain may be partially or mostly a “false alarm” based on persistent sensitization of various types, what you do differently with patients?

First, stop focusing exclusively on “fixing” patient’s tissues, because often the problem is not the tissues, but the pain experience spinning out of control. Even when there is a tissue issue, it’s all too possible that fixing it is simply impossible, that all the “tools” (treatment modalities) are largely useless,42 either entirely ineffective or, at the least, less important than the vagaries of sensation and perception.

This process can be extremely intimidating. Explaining pain is by far the most best-known strategy for dealing with it, and clinicians often feel sidelined by it, like their "toolkit" is suddenly useless. You may feel like it leaves you little to “do” to or for your patients. Professional paralysis!

The main solution to that feeling is to address the patient’s nervous system. Be kind to it. Help patients remember what it’s like to feel safe and good. Be the source of a positive sensory experience. Choose and exploit modalities not for their barely-detectable ability to change/fix tissues, but for their power to comfort and soothe, to reframe sensory experiences.

And also educate to reassure, independently of whether you “explain pain” or not — though you will find that some pain-explaining is vital for achieving that goal, with some patients more than others.

And always avoid giving patients any new cause for alarm or worry!

When the primary complaint is pain, the treatment of pain should be primary.

Barrett Dorko, Physical Therapist, online discussion, 2010

Myths and misconceptions about “Explain Pain”

Many moons ago I started trying to understand and explain pain, gradually producing this article, only dimly aware as I worked that I was re-producing some much more mature ideas.

I knew that modern pain science and treatment has deep roots, insights and research going back to the 1960s and Melzack, gate control theory and cognitive behavioural therapy, but my explaining was eerily similar to a recent and popular “packaging” of pain science known as Explain Pain (EP), from Drs. Lorimer Moseley and David Butler: “a range of educational interventions that aim to change one’s understanding of the biological processes that are thought to underpin pain as a mechanism to reduce pain itself.”43 There’s a book of that name — Explain Pain44 — and many other interpretions and riffs on the key ideas (like this article).

It’s not that I invented my own version of Explain Pain independently, despite how it looks. I was just trying to explain pain, you know? Lowercase!

Explaining Pain, according to Dr. Moseley, is about “wanting people to actually understand how and why they can be in horrible pain yet not in horrible danger.”

Photo of the hardcover version of the book Explain Pain.

Butler & Moseley’s extremely influential book, Explain Pain. The elevator pitch & the central claim of the book, from the publisher’s description: “It is now known that the more we understand pain, the less we will hurt.”

There have been a lot of misunderstandings about EP. Because explaining pain is tricky. (There are still plenty of unanswered scientific questions, too.) And because EP as a “brand” might be a bit of an over-hyped upstart, maybe given too much credit by too many people too soon — especially the idea that it actually reduces pain, which remains highly speculative. Nevertheless, for the record, here are some key misconceptions about EP …

Are clinicians becoming paralyzed by “Pain Science”?

That question was asked in a popular Facebook discussion group in early 2020. To be clear, it was not a reference to this website, but to ideas that are explored here (especially in this article), which are regularly mistaken for a treatment method (Explain Pain, either specifically or more generically).

That question attracted a lot of comments, but mine was rather popular, so I thought I’d transplant it to here, slightly edited and embellished for dramatic effect:

And what is “Pain Science” as opposed to the science of pain, exactly? Why capitalize it like a brand? What exactly are we talking about, if not “the science of pain”?

The owner of the domain PainScience.com (hint: it’s me) would really love to know what’s up with this capitalization bollocks. 😉 Because I know for damn sure that my brand is all about “the science of pain,” no capitalization, no modality or methology, no dogma or canon… just good information derived from the systematic investigation of the human experience of pain. That’s it.

If we are talking about the science of pain, then the question is effectively asking if clinicians are paralyzed by… knowing things. Are clinicians becoming paralyzed by the application of science to their work? By a modern and nuanced understanding of how pain works? Maybe they are!

But I’m sure that’s not a bad thing.

It’s true, knowledge can be paralyzing, and this has always been a challenge with evidence-based medicine: it’s hard! It’s the higher road. EBM is indeed harder than what came before. It is easier to just go with whatever witch’s brew of fact and fiction you’ve acquired from experience and mentors. Experience is especially seductive and misleading. But we do EBM not because it is easy, but because it is hard… and because it is better.

GO TO TOPCONTENTSNOTES

Pain may be a brain thing, but that doesn’t mean the body doesn’t matter

There is no zealot like a convert, and some people get so entranced by the idea that pain is an output of the brain that they seem to deny that tissue state matters at all. If you’ve been frustrated by the advocates of Explain Pain and “pain science” on social media, this section is for you. Yes, sometimes they do go too far!

All pain is indeed completely generated by your brain, technically … but that is the nature of consciousness and perception. Most sensory experiences have strong roots in the world. Which includes the flesh.

Everything is in the brain, but when we want to learn about the universe, we look through telescopes, not brain scanners.

Dr. Rob Tarzwell of One-Minute Medical School. (Ironically, when Dr. Rob wants to learn about people, he looks at them with a brain scanner.)

If you want to know about nectarines, you mostly study nectarines, not the brains that perceive them. If you want to know about that nebula, you use a telescope, not a brain scanner. And if you want to know how back pain works, you are going to have to study back injuries and pathologies as well as the creative, colourful, and dysfunctional ways that brains play with perception of backs. But brains are still usually playing with the perception of something that is actually going on in the “world” of your back — in your tissues.

Is a nebula out there? Or is it just a mirage between your ears? Trick question!

GO TO TOPCONTENTSNOTES

Sensation vs perception vs who cares

So, is pain a “sensation” and/or a “perception”? There’s a long-running debate/argument about this among pain science dorks and wonks on social media. The argument isn’t just about sensation versus perception, but also about whether it matters. Todd Hargrove tried to end the debate because he’s sick to death of it:

I tried for years not to write this post and ultimately failed. I’m sorry.

I don’t know what I like better: that he wrote it, or that he apologized for writing it. The whole thing has has gotten really tedious, and many people will groan when they see this zombie topic shambling their way yet again. Todd’s summary (which I entirely agree with):

  1. The debate is not substantive or of practical import. It does not involve disagreements about pain physiology, what causes pain, or how pain should be treated. Instead, the debate is semantic.
  2. The debate is easily resolved by simply looking at textbooks that describe how the terms sensation and perception are conventionally defined and used.
  3. These textbooks make clear that it is completely appropriate to refer to pain as a perception, and it doesn’t make much sense to say that pain is a sensation but not a perception.
  4. In any event, it doesn’t matter that much how we use these words in practice, because they are inherently fuzzy and often used interchangeably.

Good food for thought? More like food for not thinking about it ever again. But if you want to know about sensation and perception… he covers that too. Briefly. Which is all it ever needed.

GO TO TOPCONTENTSNOTES

About Paul Ingraham

Headshot of Paul Ingraham, short hair, neat beard, suit jacket.

I am a science writer in Vancouver, Canada. I was a Registered Massage Therapist for a decade and the assistant editor of ScienceBasedMedicine.org for several years. I’ve had many injuries as a runner and ultimate player, and I’ve been a chronic pain patient myself since 2015. Full bio. See you on Facebook or Twitter., or subscribe:

Part 6

Appendices

Related Reading

What’s new in this article?

2022 — New section: No notes. Just a new chapter. [Updated section: The rhythm of throbbing pain.]

2022 — Science update: Added a sidebar about the failure of phantom limb pain as a major example of pain without injury, citing Ilfeld. [Updated section: “Pain is an opinion”: Ramachandran’s excellent phrase.]

2022 — Editing: And still more minor improvements and clarifications in several sections.

2022 — Revision: Many changes to acknowledge uncertainties and controversies about the hypothesis that pain can be out of proportion to sensation, or that it can exist without any tissue damage at all. Some new citations. [Updated section: “Pain is an opinion”: Ramachandran’s excellent phrase.]

2022 — Editing: Many minor improvements and clarifications in several sections.

2022 — New section: No notes. Just a new chapter. [Updated section: Pain asymbolia: sensing without suffering, scary scrubbers, and brave mice.]

2022 — New section : No notes. Just a new chapter. [Updated section: Forgetting chronic pain: amnesia as analgesia?]

2022 — Science update: Replaced a citation to Beecher (on pain in wounded soldiers) with the correct original citation and a better summary. See Beecher. [Updated section: What goes up, must come down.]

2021 — New section: At last! This article has long needed a definition and explanation of nociception. It finally has one. [Updated section: Nociception versus pain.]

2021 — Editing: Some cleanup and clarification. [Updated section: Two very important types of chronic pain… that don’t even have names to distinguish them.]

Archived updates — All updates, including 20 older updates, are listed on another page.

This document has a complex editorial history, and the update log is a bit spotty and confused in places. Originally there was only one article, this one, which was originally and mainly about the whole “pain is an opinion” paradigm, but it also tackled the many related and thorny mind-over-pain implications. In mid 2021, the latter was moved to its own page: Mind Over Pain.

GO TO TOPCONTENTSNOTES

Notes

  1. Melzack R, Katz J. Pain. Wiley Interdisciplinary Reviews: Cognitive Science. 2013;4(1):1–15. PainSci Bibliography 54582 ❐

    This is the first of many generally relevant citations in this article. The authors, fellow Canadians Drs. Ronald Melzack and Joel Katz, have a long history of interesting research and clear writing on this topic. This is their short, technical version of the Big Idea of this article, namely that “pain is weird” and strongly “tuned”:

    Pain is a personal, subjective experience influenced by cultural learning, the meaning of the situation, attention, and other psychological variables. Pain processes do not begin with the stimulation of receptors. Rather, injury or disease produces neural signals that enter an active nervous system that (in the adult organism) is the substrate of past experience, culture, and a host of other environmental and personal factors. These brain processes actively participate in the selection, abstraction, and synthesis of information from the total sensory input. Pain is not simply the end product of a linear sensory transmission system; it is a dynamic process that involves continuous interactions among complex ascending and descending systems.

  2. The modern era of pain research was kicked off in the late sixties by the work of Dr. Ronald Melzack and Dr. Patrick Wall. All the dumbed-down pain science in this article is presented in a more scholarly form by the erudite Lorimer Moseley, an Australian pain scientist, in his excellent article “Reconceptualising pain according to modern pain science”. Dr. Moseley’s article is a great companion to this one: more science, but still far more accessible than a neurology textbook.
  3. The most common kind of presumed cause of musculoskeletal pain — a “structural” or biomechanical problem, like a slipped disc, or a short leg — is one of the least likely actual explanations. The failure of such explanations for pain to pan out over the last 20-30 years is also evidence that there’s more to pain than just screwed up tissue. See Your Back Is Not Out of Alignment.
  4. Brodie EE, Whyte A, Niven CA. Analgesia through the looking-glass? A randomized controlled trial investigating the effect of viewing a 'virtual' limb upon phantom limb pain, sensation and movement. Eur J Pain. 2007 May;11(4):428–36. PubMed 16857400 ❐
  5. Moseley L, Gallace A, Spence C. Is mirror therapy all it is cracked up to be? Current evidence and future directions. Pain. 2008 Aug;138(1):7–10. PubMed 18621484 ❐

    ABSTRACT


    Despite widespread support of mirror therapy for pain relief in the peer-reviewed, clinical and popular literature, the overwhelming majority of positive data comes from anecdotal reports, which constitute weak evidence at best. Only two well described and robust trials of mirror therapy in isolation exist, on the basis of which we conclude that mirror therapy per se, is probably no better than motor imagery for immediate pain relief, although it is arguably more interesting and might be helpful if used regularly over an extended period. Three high quality trials indicate positive results for a motor imagery program that incorporates mirror therapy, but the role of mirror therapy in the overall effects is not known. Obviously, more robust clinical trials and experimental investigations are still required. In the meantime, the relative dominance of visual input over somatosensory input suggests that mirrors might have utility in pain management and rehabilitation via multisensory interactions. Indeed, mirrors may still have their place in pain practice, but we should be open-minded as to exactly how.

  6. If you don’t get the joke, Groot is a tree-like character in the extremely successful movie Guardians of the Galaxy.
  7. Fisher JP, Hassan DT, O’Connor N. Minerva. BMJ. 1995 Jan 7;310(70). PainSci Bibliography 55248 ❐
  8. Is it for real? There is a somewhat credible source: The British Journal of Medicine. If you are determined, you can verify the citation with a free trial membership for BMJ.com. But there is not much there to verify: barely more than a photo with a caption, an anecdote included in the “Minerva” column (a compilation of snippets of interest). It is not even a formal case study.

    There is not much reason to doubt the overall veracity of the story, but there are certainly reasons to doubt that it is exactly what it seems to be, or that it actually constitutes compelling evidence of pain without damage or nociception (nerve impulses generated by potential tissue threats).

    Boot Nail Guy probably did have an unpleasant trip to the hospital despite not being seriously injured. But it is also possible that the incident did not quite play out exactly as described. Did Boot Nail Guy really need sedation? Was he actually in terrible pain, or was he just extremely anxious? Was he actually “entirely” uninjured, or could he have been just slightly injured, damage so minor that the story ignored it? It matters because a “seed” of nociception from minor injury is very different than none at all. We’ve all experienced how shockingly painful a paper cut can be, despite being a nearly invisible injury. It seems plausible to me that the whole thing was not so much perfectly uninjured person experiences terrible pain and more like slightly injured person is really freaked out until proven safe.

    Obviously this slightly formal anecdote is not compelling “evidence” of pain without any injury/nociception at all, but it can support that idea to some degree, and it can be a credible example of a sensory experience that was probably exaggerated by the mind — though I think we must still remain open to the possibility that it was more an experience of panic rather than pain. Indeed, it raises the interesting question of how to even tell the difference! If someone says they are in pain, contradicting them is not really possible (or compassionate), any more so than telling someone they are not really in love.

  9. “Nocebo” is roughly the opposite of placebo: instead of relief from belief, it’s grief from belief. The word is Latin for “I shall harm” (great supervillain slogan). It refers to the harmful effect of … nothing but the belief in or fear of a harmful effect. Give someone a sugar pill and then convince them you actually just fed them a deadly poison, and you will probably witness a robust nocebo effect. Nocebo is one of the chief hazards of excessive X-raying and MRI scanning: showing people hard evidence of problems that often aren’t actually a problem is a great way to make them suffer.

    And that is one of the main reasons it can be valuable to learn about all this.
  10. Ilfeld BM, Khatibi B, Maheshwari K, et al. Ambulatory continuous peripheral nerve blocks to treat postamputation phantom limb pain: a multicenter, randomized, quadruple-masked, placebo-controlled clinical trial. Pain. 2021 03;162(3):938–955. PubMed 33021563 ❐ PainSci Bibliography 51431 ❐
  11. It probably takes a bit of a perfect storm for a person to truly believe that they are badly injured… and yet turn out to be uninjured. And fewer still would be clear enough to justify a formal case report. Such incidents would be more of a medical novelty with no significance — interesting to pain science wonks, but probably not most doctors.
  12. Parr JJ, Borsa PA, Fillingim RB, et al. Pain-related fear and catastrophizing predict pain intensity and disability independently using an induced muscle injury model. J Pain. 2012 Apr;13(4):370–8. PubMed 22424914 ❐ PainSci Bibliography 54315 ❐

    The fear of pain was assessed in 126 brave volunteers with a questionnaire before — yikes — “inducing muscle injury to the shoulder.” (Don’t worry, nothing too awful for the subjects: they just did a workout with a lot of eccentric contraction that made them super sore.) The results were not what the researchers expected. This study is interesting because it found evidence that fear of pain before injury can predict recovery time. In other words: how well you respond to injury and recover is affected enough by fear that it can actually be predicted by measuring fear beforehand. That’s profound!

  13. Vögtle E, Barke A, Kröner-Herwig B. Nocebo hyperalgesia induced by social observational learning. Pain. 2013 Aug;154(8):1427–33. PubMed 23707275 ❐
  14. O’Sullivan S. It's All in Your Head: True Stories of Imaginary Illness. Chatto & Windus; 2015. This is one of the best single sources of detailed case studies of cases where major symptoms are clearly not what they seem, such as seizures without any of the ECG signatures of real seizures. The overwhelming takeaway of the book is that surprisingly severe symptoms surely can be created out of nothing by the power of the mind — but it also falls well short of actually proving that, and particularly with regards to pain. Most of the cases O’Sullivan describes involve some pain, but pain is never the only symptom or even the main one — and in every case it’s plausible that there is an underlying pathology driving the pain, and the "meltdown" of other symptoms caused by stress and fear are just impressive psychogenic complications.
  15. Consider the very poor example of Cozzi: “How to recognize and manage psychosomatic pain in the pediatric emergency department.” Disturbingly, the authors just assume that pain is probably psychosomatic if cannot be adequately diagnosed — by an ER physician, a relatively brief clinical relationship! — with increasing odds for teens, women, and patients with “mild intellectual disability.” Presumably these doctors would be rather unlikely to conclude that a middle-aged professional man had psychosomatic pain… or to ever spare a thought for the possibility that the a link between, say, women and pain, might be due to misdiagnosis powered by systemic sexism. This has all the same thorny social problems as profiling in law enforcement. They provide no other evidence-based basis for a diagnosis of psychosomatic pain, but claim that it “should be a positive diagnosis and not an exclusion one.” Basically the whole paper is a formal version of writing off anyone with pain who seems like one of those melodramatic chronic illness types.

    And my point here is that this is typical of the entire field of psychosomatic medicine … making it very hard to find meaningful evidence that pain can actually be psychosomatic.

  16. See Gawande: “New scientific understanding of perception has emerged in the past few decades, and it has overturned classical, centuries-long beliefs about how our brains work—though it has apparently not penetrated the medical world yet. The old understanding of perception is what neuroscientists call “the naïve view,” and it is the view that most people, in or out of medicine, still have. We’re inclined to think that people normally perceive things in the world directly. We believe that the hardness of a rock, the coldness of an ice cube, the itchiness of a sweater are picked up by our nerve endings, transmitted through the spinal cord like a message through a wire, and decoded by the brain.”
  17. Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965 Nov;150(3699):971–9. PubMed 5320816 ❐

    This is Melzack and Wall’s seminal paper arguing that (emphasis mine) “pain perception and response is triggered after the cutaneous sensory input has been modulated by both sensory feedback mechanisms and the influences of the central nervous system. We propose that the abstraction of information at the first synapse may mark only the beginning of a continuing selection and filtering of the input.” Among other things, this is the paper that described the mechanism of gate control and ultimately gave rise to the highly influential concept of the neuromatrix (Melzack).

  18. See Sensation on a Small Scale.
  19. Beecher HK. Pain in Men Wounded in Battle. Ann Surg. 1946 Jan;123(1):96–105. PubMed 17858731 ❐ PainSci Bibliography 51997 ❐

    Dr. Henry Beecher is most famous for an anecdote about treating wounded soldiers with a placebo when he ran out of morphine… which probably never happened (see Jarry). He is also famous for this classic paper, published immediately after WW II, in which he reports that most soldiers wounded in combat had so little pain that they didn’t want morphine. He hypothesized that trauma in the civilian is highly disruptive to their livelihood and causes them to focus on and feel the pain more acutely. In contrast, for the soldier, a serious injury represents deliverance from a terrifying situation — and the euphoria of this blunts the pain.

    That idea remains well-supported in broad strokes by modern pain science, but it would be quite interesting to ask if it has ever been more rigorously validated.

  20. Jackson M. Pain: The science and culture of why we hurt. Trade paperback ed. Random House; 2003.

    See also: every paper written about pain neurology in the last 20 years.

  21. Melzack R. Pain and the neuromatrix in the brain. J Dent Educ. 2001 Dec;65(12):1378–82. PubMed 11780656 ❐
  22. Younger J, Aron A, Parke S, Chatterjee N, Mackey S. Viewing pictures of a romantic partner reduces experimental pain: involvement of neural reward systems. PLoS One. 2010 Oct;5(10):e13309. PubMed 20967200 ❐ PainSci Bibliography 51708 ❐
  23. Nilakantan A, Younger J, Aron A, Mackey S. Preoccupation in an early-romantic relationship predicts experimental pain relief. Pain Med. 2014 Jun;15(6):947–53. PubMed 24716721 ❐ PainSci Bibliography 52835 ❐
  24. Goldstein P, Weissman-Fogel I, Shamay-Tsoory SG. The role of touch in regulating inter-partner physiological coupling during empathy for pain. Sci Rep. 2017 Jun;7(1):3252. PubMed 28607375 ❐ PainSci Bibliography 53159 ❐
  25. Moseley GL, Parsons TJ, Spence C. Visual distortion of a limb modulates the pain and swelling evoked by movement. Curr Biol. 2008 Nov;18(22):R1047–8. PubMed 19036329 ❐

    ABSTRACT


    The feeling that our body is ours, and is constantly there, is a fundamental aspect of self-awareness. Although it is often taken for granted, our physical self-awareness, or body image, is disrupted in many clinical conditions. One common disturbance of body image, in which one limb feels bigger than it really is, can also be induced in healthy volunteers by using local anaesthesia or cutaneous stimulation. Here we report that, in patients with chronic hand pain, magnifying their view of their own limb during movement significantly increases the pain and swelling evoked by movement. By contrast, minifying their view of the limb significantly decreases the pain and swelling evoked by movement. These results show a top-down effect of body image on body tissues, thus demonstrating that the link between body image and the tissues is bi-directional.

  26. That’s creative problem solving, but I think it only makes the impracticality point stronger: the very narrow field of view of binocs probably undermines the illusion significantly. Seeing an exaggeratedly remote looking arm through a peephole may not have the same effect. Not that it isn’t worth trying, but for this to work the brain must actually be fooled.
  27. Stanton TR, Gilpin HR, Edwards L, Moseley GL, Newport R. Illusory resizing of the painful knee is analgesic in symptomatic knee osteoarthritis. PeerJ. 2018;6:e5206. PubMed 30038863 ❐ PainSci Bibliography 53038 ❐
  28. Höfle M, Hauck M, Engel AK, Senkowski D. Viewing a needle pricking a hand that you perceive as yours enhances unpleasantness of pain. Pain. 2012 May;153(5):1074–81. PubMed 22520059 ❐
  29. Disclaimer: “To hurt is to dislike hurting” presumes a threatening context. Yet another weird thing about pain is that it is actually possible to be happy about it, which is also about the “emotional experience” of pain. If the emotional experience is positive, for whatever reason, then we can like the sensation. I can’t think of a reason. Nope. Drawing a blank here.

    But note the obvious: there are definitely limits to how much and what sort of pain can be enjoyed. Kidney stones are never sexy — no matter how much you like to be dominated.

  30. Grahek N. Feeling pain and being in pain. Cambridge, Massachusetts: MIT Press; 2007. p213

    Pain asymbolia is a condition where pain doesn’t feel bad. When people with this condition sustain an injury, they accurately sense it, and will describe the associated feeling as “pain.” But the pain is not unpleasant, and they are not motivated to avoid it. In other words, they have pain that doesn’t hurt. How can that be? The answer seems to involve damage to certain parts of the brain associated with emotion.

  31. Jahn M, Steinberg H. [Pain asymbolia-discovered around 1930 by Paul F. Schilder, almost forgotten today?]. Schmerz. 2020 Apr;34(2):172–180. PubMed 32100096 ❐ PainSci Bibliography 51369 ❐ Translated from German:

    The experience that people react very variably to comparable pain triggers — we have all done it before — is perhaps too carelessly attributed to individual physical, gender-related, psychological or cultural-religious factors. In principle, this is of course correct and important, since ancient times pain concepts and explanation models have been subject to constant change and the central nervous pain modulation, also in connection with the above-mentioned factors, has been researched for decades. But couldn’t there be a "pain symbolist" behind one or the other patient with noticeably reduced pain sensitivity?

  32. Klein C. What Pain Asymbolia Really Shows. Mind. 2015;124(494):493––516.
  33. Corder G, Ahanonu B, Grewe BF, et al. An amygdalar neural ensemble that encodes the unpleasantness of pain. Science. 2019 01;363(6424):276–281. PubMed 30655440 ❐ PainSci Bibliography 51987 ❐
  34. Pain asymbolia is not such a “blobsquatch” that there’s been serious doubt about its existence. But there are reasonable questions about how to explain the case reports we have. Jahn et al again:

    The detailed, internet-based literature research in PubMed provides relatively few articles from the last few decades, which are often individual case reports, or are of a more philosophical nature. In fact, we dare say most readers of this article have never heard of pain asymbolia before. So was Schilder wrong and perhaps presented a heterogeneous patient clientele with very different causes of pain perception disorders? After all, there are many.

    Indeed there are. But when you can demonstrate pain asymbolia by disabling neurons in the BLC, that’s a game changer.

  35. Mice can be excellent models for human physiology, but they are also infamously misleading. Hence the charming research expression: “mice lie and monkeys exaggerate.”

    But mice are better models for brain research than metabolic stuff, and in this case the BLC was targeted because we already knew something about its role in human pain, and pain system traits are generally “highly conserved” in the animal kingdom (that is, quite similar in many animals over very long periods of evolution, because they are hard to change without compromising fitness).

    But yeah… we still have to that mouse-human chasm before we break out the champagne.

  36. Choi DS, Choi DY, Whittington RA, Nedeljković SS. Sudden amnesia resulting in pain relief: the relationship between memory and pain. Pain. 2007 Nov;132(1-2):206–10. PubMed 17764843 ❐
  37. The disappearance of pain after amnesia could definitely be correlation, not causation. Both of these cases were extremely complex, humans in severe distress, with *many* potential confounding factors. They are also the only case reports of their kind that I can find. And two messy, lonely data points just aren’t enough to blow my mind.
  38. Mirza AF, Mo J, Holt JL, et al. Is there a relationship between throbbing pain and arterial pulsations? J Neurosci. 2012 May;32(22):7572–6. PubMed 22649235 ❐ PainSci Bibliography 51402 ❐
  39. For instance: my friend who had an almost literally invisible cyst pressing on a nerve root, a pathology that could only be seen if you looked in just the right way, with just the right kind of imaging. Until diagnosed, he was treated by more than one healthcare professional as a dysfunctional chronic pain case — but it was actually a clear cut case of chronic-acute pain, not dysfunctional at all, not a false alarm at all.

    It was just hard to diagnose.

  40. It’s not academic hair-splitting. It doesn’t mean that pain isn’t real, or that tissues can’t genuinely be in trouble. What it means is that all pain — always, no matter what — is an unreliable interpretation of information coming to your brain from your body. Just like your brain “constructs” the reality that you see and hear and touch, it also constructs the experience of pain.
  41. TheConversation.com [Internet]. Moseley L. Pain really is in the mind, but not in the way you think; 2013 Jul 20 [cited 14 Jan 6]. PainSci Bibliography 54649 ❐
  42. I’m understating that, because I don’t want to blow too many minds. The idea that there might be little or nothing that anyone can do to “repair” tissue in any meaningful sense is a radical concept for a lot of professionals. I suspect there are a handful of possible examples, but the point is that almost all forms of manual and physical therapy, most of the time (whether we know it or not) are almost exclusively inputs to the nervous system. And “results” are the CNS responding with a new story. The tissue state remains the same, or only trivially changed. Flesh is remarkably good at staying just the way it is. (With a gradual, inexorable drift back towards homeostasis after injury.)
  43. Moseley GL, Butler DS. Fifteen Years of Explaining Pain: The Past, Present, and Future. J Pain. 2015 Jun. PubMed 26051220 ❐

    A cogent formal summary and update on how this “explain pain” thing is going so far (pretty well). Moseley and Butler are always quite readable, even when writing for journals (imagine), but see also their blogging about the same thing.

  44. Butler D, Moseley L. Explain Pain. 2nd ed ed. Noigroup Publications; 2013.
  45. This misconception comes straight from some overzealous advocates of Explain Pain, who often vigorously promote the idea that pain is actually “unrelated” to tissue damage, or does not “correlate” with it “at all” — perhaps too vigorously. I have often seen claims that exaggerated. It’s true and important that the correlation between tissue damage and pain is often poor, but it is still clearly quite strong for most people most of the time.
  46. The central message of explaining pain is that pain often exaggerates the danger that tissue is in. In the phenomenon of “central sensitization,” the exaggeration is pathological and entrenched: danger signalling is consistently and severely exaggerated. But that’s an extraordinary situation. Pain is also routinely out of proportion to the danger even when there is absolutely no pathological sensitization going on at all, thanks solely to the brain’s power to modulate pain.

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