Chronic Pain as a Conditioned Behaviour

Can chronic pain be a “learned response” to things that shouldn’t hurt? It’s an interesting idea, with obviously optimistic implications. What is learned might also be un-learned! Unfortunately, we do not know if pain actually ever works this way, and it’s controversial — like practically everything about the science of pain. But it’s an interesting idea that it’s worth discussing and exploring regardless of whether it is true.

Conditioned behaviour refers to a physiological or emotional response to an arbitrary stimulus via the well-studied psychological phenomenon of classical conditioning. It’s a business-as-usual response to something that wouldn’t normally call for it. For instance, if we hear a bell every time we eat a cookie, soon our brains think bell equals cookie, and darned if we don’t start to reacting to that bell as if a cookie is imminent: happiness, salivation! It’s cookie time! New signal, same old behaviour.

We can be conditioned to link any stimulus with many kinds of responses. There are many fascinating examples in the history of psychology. It’s a potent and cool phenomenon, a cousin to placebo weirdness.

A particularly relevant example is that anxiety can be a conditioned response, and it seems like it might be a short hop from anxiety to psychosomatic symptoms, which may include pain. Or it might not! Whether anxiety is painful is a related controversy. But if anxiety can be painful, then this is a key point in the case for the chronic pain as a conditioned response.

Can pain be conditioned? The plausibility

It’s amazing how many professionals believe that pain can be conditioned — most of them, at least 80%.1 It’s quite an implausible idea, with little science to back it up. Not that a lack of evidence ever stopped anyone from believing anything!

The plausibility is low because we do know that conditioned responses are generally behavioural, physiological, and emotional — hunger, fear and anxiety, or excitement — not sensations. We can’t be conditioned to sense things that do not exist, cannot learn to hallucinate on cue: smell a pie baking, see a walrus, hear a fart. So why would it be possible to learn to feel pain?

There might be some answers to that question — pain is quite complex, and there is plenty of controversy about how it works.2 The point is that all such answers are still just speculative for now. Conditioned pain is a somewhat extraordinary claim about how humans work … and most such ideas turn out to be wrong.3 And there’s still no compelling, direct evidence that can settle it.

The evidence for pain conditioning … such as it is

A 2023 trial by Kang et al. is one of the few direct tests of pain conditioning to date, repoting that “conditioned pain may exist, albeit most likely in rare cases or under specific situations.”4 That “may exist” conclusion — damning with faint praise? — is at least consistent with a 2016 review of what little other direct evidence exists.5

But it’s really not enough to go on, and Kang et al. has been strongly criticized by some experts, arguing that the results are meaningless because the test was “rigged.”6 This is a strong disagreement between experts; non-scientists can’t pick a winner.

The most clearly negative direct test of conditioning pain was from Madden et al. in 2017. In the experiment, subjects did not “learn” pain from a combination of vibration with painful heat.7 Their pain thresholds actually got higher! But the conditions were very specific, and the researchers correctly point out that “allodynia might be induced under different conditions—perhaps with different stimuli, different anatomical sites, or different conditions of implicit threats.” And so, more tests like these are going to be needed to get to the bottom of this.

It might be futile, though. Pain conditioning may be hard to cook up in the lab — and that might be an understatement. Every trial that tries to demonstrate classic conditioning of pain is in vitro, an experiment “outside a living organism,” because the real world conditions that might lead to conditioning are just too complex and volatile to mimic. This casts unresolvable doubts on the conclusions of any trial that fails to detect conditioning. Studying the conditioning of pain might be like trying to study the ecology of a jungle by trying to reproduce and standardize a few key aspects of it — just too many unknown variables. But that also makes the idea unfalsifiable in practice, a hypothesis that will haunt us forever, a bogeyman that cannot be confirmed or banished; those who believe can always protest, “The real thing exists, but it’s too exotic and elusive to catch on film,” like Sasquatch. But weird and elusive things do exist in nature!8 Many psychological and neurological phenomenon are practically impossible to induce experimentally: déjà vu, false memories, giggling fits, frisson, synesthesia, and so on. There is no solution to this puzzle except to continue gathering as much relevant data as possible. Sometimes we just can’t know how things really are. Or not for a long time.

The only other evidence of conditioned pain is indirect — which can keep hope alive for those who both believe in it and follow the science (so probably not many).910111213 But there’s a huge gap between research that shows that conditioned pain might be possible and research that shows that it actually is.

So it’s all a bit squishy and inconclusive, mostly just an absence of evidence, and not evidence of absence — and so the existence of this phenomenon remains a matter for speculation, debate, and scoffing at people who disagree.

So that’s the evidence situation! Such as it is. Now back to the (interesting!) speculation…

Just a little classical conditioning humour. I laughed on cue.

Sensation versus perception

Chronic pain is notoriously a different beast than acute pain, and we still have a lot to learn about how it works — enough that there’s probably still room for a major insight like “it might be a conditioned response.” It’s broadly plausible based on what we know about chronic pain.

Pain is an experience made from a fairly predictable sensation that has to pass through the complex filter of perception, countless contextual factors that “tune” the experience of pain, dampening or amplifying it, or changing its quality. Acute pain is usually almost pure sensation, with only a little perceptual modulation — stepping on a piece of lego causes strong pain for basically everyone. But even with acute pain, there are examples of perception overriding sensation to a surprising degree.

And with chronic pain? A big story of pain science over the last few decades is that perception might be a substantial factor chronic pain. This is disputed and debate, but it’s probably mostly a question of how true it is.

Pain as a conditioned behaviour is one possible mechanism for how that works: that we can learn to perceive pain even where there is little or no sensation left to base it on. If pain can be learned, it’s might be mainly perception we’re learning — but that can be powerful, and we know that it can probably defy sensation.

There are three main types of pain. There is still a lot of room for speculation and debate about the nature of the “other” category. If pain can be a conditioned behaviour, it’s part of that “other” circle.

Some “simple” psychosomatic pain might be a good example of conditioned pain

If there’s any such thing as psychosomatic pain at all.

It’s a dangerous game diagnosing anyone’s pain as psychological or “just a perception,” because there are so many hard-to-diagnose organic conditions that do cause long-term pain (the sensation).14 One of the worst things any healthcare professional can do is imply that a patient’s pain is their “fault” in any way. But I’m not prepared to be so extreme with that caution that I ignore reality.

The uncomfortable truth — for every compassionate person, patient or pro — is that there is indeed such a thing as psychosomatic illness and disability. Although it’s unclear whether or not pain can also be generated/exaggerated by the mind, it is likely true to some degree. The functional neurological disorders (FND, formerly “conversion” disorders) are the most dramatic example of the extraordinary power of the mind to make us suffer. They are all too real.

If such dramatic psychosomatic symptoms exist, then they also exist in smaller doses — one ingredient in a pain cocktail.

It’s also quite clear that these symptoms are a kind of “behaviour,” and equally clear that many of them are predictably triggered by specific non-painful stimuli. And this is a fairly obvious extension of the universal human experience of physical responses to psychological stimuli.15

Blushing occurs when the blood vessels of the head and neck dilate and become infused with blood. It is an instantaneous physical change seen on the surface but reflecting a feeling of embarrassment or happiness that is held inside. When it happens I can’t control it. That point is important. My blushes betray a feeling and, even when they increase my embarrassment, I cannot stop them.

It's All in Your Head, by Suzanne O’Sullivan, 3

We can try to extrapolate from “I always blush in this situation” to “I always hurt in this situation.” The undeniable existence of the former suggests that it pain could also sometimes be a conditioned response.

Another perspective on this is that psychosomatic symptoms are a form of anxiety disorder… and anxiety as a classically conditioned response is already a well-established idea.16 And I know how this can go from personal experience, alas.17

Threat hyper-vigilance as a driver of pain as a conditioned behaviour

Pets are selected both naturally and artificially for snack hyper-vigilance. Hoomans are a good source of food! When we deliver the goods, our pets care about the context in which it happened way more than we do: every nuance is remembered, many subtle sensory details we are completely oblivious to.

Like the very spot you were standing in when it happened…

“Remember.”

Thanks to artist Jimmy Craig of TheyCanTalk.com for granting permission to use this perfect, poignant illustration of snack hypervigilance.

They remember! And they watch for the signs! Intensely! You never know how a snack will happen, but it’s most likely to happen much like it has before.

Like pain? You can see where this is going.

How our brains might be like that cat

Our animal brains do this too, obsessively filing away every detail they can about the circumstances of rewards… and threats. Definitely threats, too. If brains could talk, they would regale us with all the absurdly specific and subtle details they remember about past threats and rewards. It’s probably most of what’s going on under the hood for most animals, most of the time.

When something hurts a lot, our brains pay Very Close Attention to how it happened, and then we spend a long time “watching for the signs.” And yet, weirdly, we are mostly oblivious to those signs. Our conscious minds are filled with all kinds of wonders and nonsense. But our brains? Our brains are as focused as that cat:

“Remember when I stood in that exact way and I was in terrible pain?” the brain asks. The mind is barely even paying attention.

“I do,” says brain, and of course it does. Pain is most likely to happen much like it has before, and our brains know it even when we don’t.

How much are we puppets of threat hyper-vigilance? Is it part of the mechanics of how pain works?

Threat hyper-vigilance is well-established psychology. The reality of it does not mean that pain can actually be conditioned… but, if pain can be conditioned, it’s a safe bet it’s because threat-hypervigilance is a potent force. If we do learn to hurt, it’s probably because our brains recognize the circumstances of past pain… and helpfully “warn” us about it … with more pain.

Amnesia as analgesia: can you forget chronic pain?

Back in 2007, Choi et al. reported two cases of amnesia (with different causes) preceding relief from severe chronic pain and the end of any need for opioid management.18 The profound implication is that amnesia relieved the pain. 😮

Unfortunately, these stories may not be what they seem, and it’s hard to take them too seriously.19 But what if amnesia actually did give those people relief? It may be safe to assume, but it is the most obvious explanation.

It would suggest that chronic pain is forgettable, and therefore that it was a function of the mind to begin with — not necessarily a “conditioned behaviour,” but something that was learned in some sense, constructed by our brains and therefore dependent on them.

If so, that would not necessarily 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.

I do not take those two case studies at face value. But they are fascinating, they do potentially contribute to the concept of pain as a conditioned behaviour, and I will not forget the possibility that some kinds of pain can be forgotten.

Disrupting the pain habit

Sensory Disruption of Reconsolidation (SDR) is an experimental chronic pain therapy method pioneered by Christine Sutherland, an Australian behavioural therapist and researcher. At first glance, SDR looks like exactly the sort of thing I am most likely to scoff at: a treatment modality based on an extraordinary claim, namely that true chronic pain mostly consists of conditioned responses of the brain and central nervous system, and that these conditioned responses can be “extinguished” rapidly and permanently.

Note that terms like “disrupted” and “extinguished” might sound like marketing colour, they are actually technical terms — classical conditioning jargon.

The brain is quite “plastic.” What is learned might be un-learned. Or disrupted.

If that’s true, it would be a big deal! So I am not a “believer” in SDR — not without evidence! — but I have been persuaded to at least respect the effort. I have been convinced by her humility and intellectual honesty, demonstrated to me in many emails over many years. This is a rare example of a treatment modality founder who clearly understands that her method is experimental. For instance, she knows that therapists tend to over-estimate their own efficacy.20 So why is she doing it? Because she thinks it’s an interesting and worthwhile experiment, and there's nothing wrong with experimental therapy with informed consent.

Few pain treatments work out, and SDR could easily fail if it is ever tested in a rigorous trial. Meanwhile, it has interesting bones and it’s something I want PainScience.com readers to know about. The rest of the article is devoted to this unusual example of an experimental pain treatment.

Exactly what SDR looks like

SDR consists of exposure to highly specific conditioned stimuli associated with the pain experience, such as specific thoughts or perceptions linked to the pain — language, metaphor, meaning, beliefs, etc — while simultaneously introducing “disruptive” sensory stimulation (literal and/or imagined). Now in more detail:

• A lot of chronic pain may be a learned response (classical conditioning) to harmless stimuli, and can be unlearned quickly and easily in principle, with a kind of mental hack: “disruption of the reconsolidation phase of the response.”
• “Reconsolidation” refers to the neurological process of regenerating a link between a stimulus and a behaviour. And that process can be disrupted by juxtaposing the conditioned response with a strong sensation — almost any sensation as long as it is a vivid one, with good timing. This disruption is a fairly well-studied phenomenon; when it occurs, reconsolidation fails completely, and the conditioned response simply ceases to exist! It’s like knocking the baton out of a relay racer’s hands just as they are passing it. (This is fascinating stuff whether it has anything to do with pain or not.)
• So SDR therapy attempts to artfully evoke both reconsolidation and ways to disrupt it. A simplified example: focusing on thoughts and feelings that are precisely linked to the pain can trigger reconsolidation, and then it can be disrupted with contrasting behaviours and stimuli, such as a physical action (a slap, a hop, or a pinch), and visualization of a nice sensory experience (like petting your cat). The conditioned response has to be “caught in the act” of reconsolidating. If reconsolidation isn’t occurring, there is nothing to disrupt!
• The results of this process can seem simple, but getting it right is a lot like a plumber who solves a problem “easily” by knowing exactly what to do. For most people, disruption can only be achieved in a context of more comprehensive therapy — it takes real skill to identify and guide people through the identification and exploration of their triggers, and finding and interjecting the most apt and practical disruptive factors, and with good timing.
• And that’s not all! Pain is complex, and the more entrenched and severe it is, the more finicky this process can be. So SDR therapy also involves more conventional approaches to pain chronicity, by addressing major risk factors like sleep dysfunction, stress, poor nutrition. None of these are what makes SDR unique, but they are still important.

Similar to EMDR, EFT, NLP? Nope! Several things SDR is not

SDR is superficially similar to Eye Movement Desensitization and Reprocessing, Emotional Freedom Technique, and Neuro-Linguistic Programming — all notoriously dubious psychotherapeutic modalities that skeptics have been warning people about for a long time. But the theory and principles of SDR are not the same. Christine says that she was once “one of the ‘energy psych’ crew, so I understand their perspective, as much as it frustrates me at times.” But she left that world behind, and SDR is a different kettle of fish.

SDR is also often confused with “distraction,” “desensitization,” “inhibition,” “habituation,” or “exposure therapy.” These all related or similar concepts, but none of them is quite the same as what’s going on with SDR. It’s important to understand that disruption of reconsolidation is a very specific neurological phenomenon, and quite obscure.

DIY SDR? Can you do this for yourself?

Mostly no — too many cases are too complicated and difficult. An expert guide is probably needed for any result in most cases, let alone best results. And, of course, finding someone trained in SDR therapy to help you is going to be difficult. This isn’t a well-known modality.

The primary utility of this information for my readers is mostly just that it has some interesting implications for how chronic pain works, knowledge that is inherently valuable. It is good to know things. (“It’s what I do. I drink and I know things.” ~ Tyrion Lannister)

That doesn’t mean you can’t try some self-serve SDR though. Here’s the self-serve version:

1. Study your pain. Keeping this technique and the phenomenon of classical conditioning in mind, explore your experience. This phase could go on for days or weeks. Your ultimate goal is to trigger reconsolidation so that you can disrupt it: to actually recreate the link between a trigger and the pain. Therefore, you need to understand your triggers as well as possible. And they could be subtle! Once you believe you have a fairly good idea what constitutes a conveniently reproducible trigger for your pain…
2. Invoke reconsolidation as best you can. This is a quick step, taking a few minutes at most. You focus on the trigger and the feelings you expect/fear it will create. This is largely a mental/meditative process, but could also involve an action or physical situation. And then, when you judge that you are right in the middle of rebuilding the link between the trigger and the pain…
3. Disrupt reconsolidation! Like continuing to stir a sauce while adding a new ingredient, continue to focus on the link but mix in something completely different: a physical action, a vivid sensation, probably something pleasant, probably something functional.
4. Repeat at semi-regular intervals. A sensible “dosage” might be twice a day for a week. Less risks failure due to simply not having enough disruption. More risks wasting too much time and energy on a highly experimental treatment.

Finally, do not neglect the broader context of your chronic pain! This is all probably doomed to failure if it’s done in a therapeutic vacuum. Most chronic pain patient are embroiled in extensive stresses and vulnerabilities. It’s important to tame those as well as you possibly can, both for the sake of this experiment … and just because it’s important for chronic pain patients regardless of SDR.

My utterly unscientific self-treatment anecdote

Clearly the DIY approach could easily fail even if professionally guided SDR proves to be genuinely effective. But I wouldn’t hesitate to try it myself if I needed to… and I have, and it worked extremely well for me … once.

In only about three sessions, I “nuked” an extremely persistent case of hip pain (greater trochanteric pain syndrome, seemingly). It had been unrelenting for months and had started to interfere with sleep. This was not a subtle or erratic pain that might have just happened to have backed off by chance or with a little optimism: it was a serious, constant problem that evaporated entirely right after I took a swing at it with SDR.

It seemed remarkable! And that experience is probably chiefly responsible for the energy I’ve put into this article. Although I was intellectually interested before that, relief from a really nasty hip pain was quite inspiring.

I hope I’ve been clear that the DIY approach is far from guaranteed to work — I am loathe to inspire false hope — and yet I seem to have succeeded on my first try. Just lucky? Maybe I’m a natural at this? The only honest answer is “I don’t know,” of course. It certainly could have been dumb luck, and might as well have been for all the insight I have into it. Perhaps my success had something to do with the type of pain: it might be easier to achieve this with a particularly focal pain, easier to focus on? I’m reaching. I simply have no idea.

It’s a frustrating way to conclude, but I should add that a few subsequent experiments have failed. This is a common experience with many kinds of pain treatments, I think: initially good results, followed by disappointment. We could hypothesize that the novelty and optimism of a new-to-you treatment packs a fairly strong placebo effect, but I don’t really know what it’s about.

About Paul Ingraham

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:

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Related Reading

• 38 Surprising Causes of Pain — Trying to understand pain when there is no obvious explanation
• Anxiety & Chronic Pain — A self-help guide for people who worry and hurt
• Sensitization in Chronic Pain — Pain itself can change how pain works, resulting in more pain with less provocation
• Pain is Weird — Pain science reveals a volatile, misleading sensation that comes entirely from an overprotective brain, not our tissues
• Mind Over Pain — Pain can be profoundly warped by the brain, but does that mean we can think the pain away?
• Vulnerability to Chronic Pain — Chronic pain often has more to do with general biological vulnerabilities than specific tissue problems
• The 3 Basic Types of Pain — Nociceptive, neuropathic, and “other” (and then some more)
• Pain Relief from Personal Growth — Treating tough pain problems with the pursuit of emotional intelligence, life balance, and peacefulness

Notes

1. Madden VJ, Moseley GL. Do clinicians think that pain can be a classically conditioned response to a non-noxious stimulus? Man Ther. 2016 Apr;22:165–73. PubMed 26794284 ❐

   In one of the author’s own words in an IASP blog post:

   We put [the idea of conditioned pain] to 1090 practising healthcare clinicians, representing 57 different countries, in an online survey. … First, we filtered out those who thought that pain cannot occur without nociception [danger signals], because that would logically preclude them from endorsing a classical conditioning framework for pain. Encouragingly, 86% of our respondents (accurately) stated that pain can occur without nociception. Hooray for pain science education! Of that 86%, 96% believed that pain can be a classically conditioned response to a non-noxious stimulus. Now, that is an astonishingly high percentage. It works out to approximately 94% of all the survey respondents endorsing a classical conditioning framework for pain.

   We were interested in what these clinicians thought their views were based on, so we asked them whether or not they thought there was evidence to support their view. Of those who endorsed the classical conditioning framework for pain, 98% believed that their endorsement was based on scientific evidence.

   So 96% of clinicians who believe pain can occur without nociception… but presumably 0% of the clinicians who do not think that pain can occur without nociception. 😜 That’s about 82% of all clinicians.

2. For instance, the key to the phenomenon, if it exists, might be related to the fact that pain is interoceptive (sensing things inside the body), and interoception might be fundamentally more susceptible to conditioning than exteroception (sensing the outside). Nevertheless, the fact that conditioning just generally doesn’t involve tinkering with sensations at all is a large conceptual hurdle — so large that it should make anyone hesitate to “believe” in conditioned pain without really good evidence.
3. Null hypothesis primer: The null hypothesis is a formal way of saying that most ideas about complex things turn out to be wrong, and a rigorous (scientific) test will probably find nothing (null). “The null” is usually confirmed in science, because there are just too many things we still don’t know, and human ideas about how things work are badly polluted with all kinds of biases and foolishness. Our ideas about health (a very black box) are particularly sketchy. And so most medical trials of have negative results — or positive results that are errors powered by wishful-thinking, doomed to be overturned by more rigorous studies. Understanding that it’s unwise to bet against the null is like knowing that “the house always wins.”
4. Kang S, Van Ryckeghem DML, Vlaeyen JWS, De Paepe AL, Crombez G. In search of conditioned pain: an experimental analysis. Pain. 2023 Nov;164(11):2596–2605. PubMed 37288937 ❐

   This paper presents a trio of related experiments to test the hypothesis that pain can undergo classical conditioning. In preparation for the experiment, participants were trained in a simulated setting to anticipate pain when touched on the hand with a blue pen, but not when touched with a yellow pen (“acquisition”). In the first test, the shock was happened when the pen touched a specific point on the hand; in the second, it was when the pen seemed to touch the hand in the virtual world; and in the third, the participants were told the pen could cause pain instead of just signaling it. This process definitely taught subjects to expect pain when they saw the blue pen, but only the second and third tests showed “some evidence” of actually feeling pain when a shock was not delivered. The results suggest that it’s possible for people to learn to feel pain from certain cues, but it might be quite rare or only happen in certain conditions.

5. Madden VJ, Harvie DS, Parker R, et al. Can Pain or Hyperalgesia Be a Classically Conditioned Response in Humans? A Systematic Review and Meta-Analysis. Pain Med. 2016 Jun;17(6):1094–111. PubMed 26814278 ❐
6. Cohen M, Quintner J, Weisman A. "Conditioned pain" remains unproven and unlikely (comment on Kang et al. PAIN 2023; 164: 2596-2605). Pain. 2024 May;165(5):1189–1190. PubMed 38619935 ❐

   A letter expressing strong criticism of Kang, arguing that the results were biased by the language. The substance of the letter is condensed into this bit of tweeting by co-author Asaf Klas Weisman, a PhD candidate (2023) at Tel Aviv University:

   “I would change the name of the study to: ‘In search of conditioned pain: A monumental WASTE of time.’ The discussion of the authors who performed 3 different experiments is quite honest in admitting that they were not really successful and that the risk of reporting bias is too big. Additionally, they did not attempt to control demand characteristics (DC). Hence, the supposedly positive results in 2 experiments are suspected to be artifact of lack of control for DC.

   So, even in light of “positive findings” in 2 out of three experiments, those results do not support the hypothesis. The idea of conditioned pain is nonsense.

   In a follow-up comment, he suggests that more research is…

   “…a waste of time because an experience cannot be conditioned. Do you think I can condition your experience of the color red to be green?”

   The authors respond. They do not deny that they failed to control for demand characteristics, but dispute that it’s a serious flaw.

   This is a strong disagreement between experts. As observers, we simply cannot know how informative Kang et al.’s experiment really was.

   I’m quoting Mr. Weisman for the sake of acknowledging “who disagrees and why.”

7. Madden VJ, Russek LN, Harvie DS, Vlaeyen JWS, Moseley GL. Classical Conditioning Fails to Elicit Allodynia in an Experimental Study with Healthy Humans. Pain Med. 2017 Jul;18(7):1314–1325. PubMed 27688310 ❐

   This trial was a rare direct test of whether classical conditioning could induce pain from non-painful stimuli in humans, via the mechanism of classical conditioning. First, Madden et al. combined non-painful sensory stimuli (vibration) with painful heat in 34 participants. They were trying to “teach” the subjects that vibration=pain. Then they checked to see if their pain thresholds had in fact been reduced for the conditioned stimulus, by applying vibration alone.

   It didn’t work: there was no statistically significant reduction in pain thresholds. On the contrary, they went up! A habituation effect, probably (see May) — the actual opposite of being conditioned to feel more pain when vibrated, these subjects were “conditioned” to feel less pain. (And that effect is worth understanding, regardless of the implications for conditioning of pain.)

   Importantly, there was no effect from factors like gender, pain catastrophizing, and a lousy mood (“negative affect,” prone to fear, sadness, anxiety).

   The study concludes that classical conditioning definitely did not induce allodynia under these conditions, but also makes it clear “this is isn’t over,” more research really is needed:

   Importantly, this study does not provide conclusive evidence that allodynia cannot be induced using classical conditioning — only that the present carefully designed paradigm did not induce allodynia in this sample. It remains possible that allodynia might be induced under different conditions — perhaps with different stimuli, different anatomical sites, or different conditions of implicit threats.

   Indeed, all the key limitations of this study cast a bit more doubt on whether the conditions of the trial could possibly be fertile ground for growing a crop of conditioned pain:

   1. Timing! The “simultaneous” pairing of stimuli was not perfectly aligned, so maybe the conditioning wasn’t good enough.
   2. Vibration? Visual and auditory stimuli might have worked better (as used in other studies).
   3. Masking! While participants were blinded — an important feature of any trial — being unaware of the pairing might have sabotaged the conditioning a bit. (But is awareness required for classical conditioning in this context? Unknown!)
8. The ocean depths are full of creatures that are extremely impressive in their element, but they literally fall apart when brought to the surface in nets, becoming gelatinous shreds that could be anything. Imagine trying to “prove” the existence of such animals without sophisticated submersibles! Until we could meet them where they live, these lifeforms were effectively immune to investigation, as cryptic as Sasquatch or Nessie — and yet they are absolutely real.
9. Flor H. New developments in the understanding and management of persistent pain. Curr Opin Psychiatry. 2012 Mar;25(2):109–13. PubMed 22227632 ❐

   This paper explores evidence that people with chronic pain have altered brains and wonky perception. They “propose” this because the evidence is indirect and incomplete. The brain changes seen in pain patients certainly exist, but their meaning is unclear: they might be cause and/or effect, and they may or may not have useful clinical implications. But this author believes that they “require new treatments that focus on the alteration of central pain memories and maladaptive body perception.”

   If so, that would constitute fairly strong supporting evidence that pain can arise from classical conditioning.

10. Simons LE, Moulton EA, Linnman C, et al. The human amygdala and pain: evidence from neuroimaging. Hum Brain Mapp. 2014 Feb;35(2):527–38. PubMed 23097300 ❐ PainSci Bibliography 52566 ❐

    This is a review of studies of role of the amygdala in processing pain. The amygdala is a brain region associated with memory, emotion (most notably fear and anxiety), and decision-making. And it “lights up” (the inevitable metaphor) differently in pain patients than healthy people, and there are even distinctive differences between types of pain. For instance, the authors report that clinical pain (as opposed to experimentally induced pain) results in activation of the laterobasal region, which is “suggestive of the cognitive-affective overlay present among individuals suffering from chronic pain.”

    The most prosaic interpretation of this is not that the amygdala is actually modulating pain (which cannot be shown by this data), but just that people have thoughts and feelings about it. Imagine!

    This does not show that conditioned pain is possible, but it does show that the amygdala could have a modulatory role — and that might be how classical conditioning could cause pain.

11. Mlekusch S, Neziri AY, Limacher A, et al. Conditioned Pain Modulation in Patients With Acute and Chronic Low Back Pain. Clin J Pain. 2016 Feb;32(2):116–21. PubMed 26741741 ❐

    Low back patients may have an impaired ability to neurologically control their own pain, and that idea is supported by this test of several dozen acute and chronic cases, compared to some healthy people. Specifically they found reduced “conditioned pain modulation.” This provides some evidence for “disturbed endogenous pain modulation.”

    Note that “conditioned pain modulation” is a very specific phenomenon that doesn’t have anything directly to do with classic conditioning of pain (just an odd naming coincidence). However, the evidence of “disturbed endogenous pain modulation” lends indirect support for conditioned pain.
12. Elman I, Borsook D. Threat Response System: Parallel Brain Processes in Pain vis-à-vis Fear and Anxiety. Front Psychiatry. 2018;9:29. PubMed 29515465 ❐ PainSci Bibliography 51612 ❐
13. McCarberg B, Peppin J. Pain Pathways and Nervous System Plasticity: Learning and Memory in Pain. Pain Med. 2019 Dec;20(12):2421–2437. PubMed 30865778 ❐

    A review of the literature on the neurobiology of the relationship between memory and pain, concluding that pain can be modulated substantially by cognitive and emotional inputs, and thus “chronic pain can be seen as persistence of the memory of pain and/or the inability to extinguish painful memories.”

    These conclusions lend significant support to the hypothesis that classically conditioned pain is possible.

14. Ingraham. 38 Surprising Causes of Pain: Trying to understand pain when there is no obvious explanation. PainScience.com. 18963 words.
15. O’Sullivan S. It's All in Your Head: True Stories of Imaginary Illness. Chatto & Windus; 2015.

    This book consists mainly of well-told stories of severe psychosomatic illness and functional neurological disorders (neurological symptoms without diagnosable disease). The key take-away is that psychologically powered illness is common and can be amazingly severe. Although Dr. O’Sullivan is clearly concerned about the risk of incorrect diagnosis, and she is cautious and compassionate enough that I think she mostly gets it right (with the notable exception of the chronic fatigue chapter). It’s well-written and fascinating and has plenty to offer. I do wish there were citations.

16. Anxiety is not a well defined part of the human experience, and never has been. People have been arguing about its nature for millenia: is it a philosophical problem or a biological one? Driven by nature or nurture? Congenital or acquired? Anxiety disorder is well described, but not well understood. One possibility that has been taken seriously by many experts for decades is that it is a classically conditioned behaviour: a learned response to things that shouldn’t be so scary. When anxiety is about our health (hypochondria), we can easily generate a wide variety of psychosomatic symptoms that are terrifyingly real to the victim. So we can probably learn to experience symptoms as a response to all kinds of subtle cues — and one of those symptoms can be pain. Therefore, if anxiety can be a conditioned response, so can pain.

17. In 2015, I had a rough time with withdrawal from an accidental addiction to benzos. Benzo withdrawal can cause both strong anxiety and bizarre, hallucinatory symptoms. I suffered greatly, reacting fearfully to strange sensations dozens of times a day for weeks. My standard reaction was basically “that sinking feeling,” a swoon of dread, but the swoon became just another symptom to be afraid of: rather than perceiving it as fear, I experienced it as a woozy, sickly exaggeration of whatever little sensation triggered it. Small ordinary pains almost instantly turn into bigger, weirder ones. It’s basically exactly like being alone in a scary old house and overreacting to every noise and shadow, perceiving what you fear rather than what is actually there.

    The withdrawal slowly eased, but the damage was done: I had learned to respond to odd sensations with nervous reflections of them, many of them painful.

18. 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 ❐
19. 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.
20. Tracey TJG, Wampold BE, Lichtenberg JW, Goodyear RK. Expertise in psychotherapy: an elusive goal? Am Psychol. 2014 Apr;69(3):218–29. PubMed 24393136 ❐

    I know Christine knows this, because I got this reference from her. She summarized it in one of her own papers about SDR: “therapists tend to over-estimate their expertise, and also over-estimate effect size (if any) of the treatments they provide.” Yep. Exactly right! And that’s the kind of humility and self-awareness that earned my trust.