Oh pain, where art thou?

We found the spot

In March 2015, a group of researchers (Segerdahl et al 2015) from the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain published a paper in Nature Neuroscience entitled The dorsal posterior insula subserves a fundamental role in human pain (sorry, behind a paywall). The researchers took 17 healthy human subjects, applied a capsaicin cream to their legs and stuck them in a big magnet (fMRI). A clever part of the design was the use of capsaicin cream to induce a dynamic pain experience – when the cream is first applied it is quite innocuous, but over time it begins to feel warm, then hot, then painfully hot.  Segerdahl et al (2015) looked at how brain activity changed as the subjects’ reports of pain increased (and decreased) over time.

Segerdahl et al (2015) reported:

“Human neuroimaging studies that measure how nociceptive inputs are encoded to produce pain experiences have yet to identify regional activity specific to pain. Many cortical regions are activated, but pain is a multifactorial experience that encompasses altered attention, anxiety, threat and many other non-specific features reflected in these activations. Despite extensive study using sophisticated psychological and pharmacological procedures that aim to disambiguate pain-specific from nonspecific components, we have yet to identify a pain-specific brain region. Part of the difficulty relates to limitations of neuroimaging tools and confounds in protocol designs.

…we were able to identify the dpIns [dorsal posterior insula] as subserving a fundamental role in pain and the likely human homolog of the nociceptive region identified from animal studies. Future work targeting dpIns activity might provide a window to explore fundamental mechanisms related to how pain emerges from nociception as well as new therapeutic approaches to treating certain chronic pain conditions.”

The ‘Ouch zone’

The press around the study was, however, a bit more ‘robust’ than the findings may have lead one to believe. The University of Oxford published a press release suggesting:

‘Ouch zone’ in the brain identified

“The results, published in the journal Nature Neuroscience, show that activity in only one brain area, the dorsal posterior insula, reflected the participants’ ratings of how much the pain hurt.

We have identified the brain area likely to be responsible for the core, ‘it hurts’, experience of pain,’ said Professor Irene Tracey, University of Oxford, whose team made the discovery. ‘Pain is a complex, multidimensional experience, which causes activity in many brain regions involved with things like attention, feeling emotions such as fear, locating where the pain is, and so on. But the dorsal posterior insula seems to be specific to the actual ‘hurt level’ of pain itself.'” (emphasis added)

It certainly behooves the author of a press release (or blog post…) to write a snappy, attention grabbing headline, but, the transition from “we were able to identify the dpIns as subserving a fundamental role in pain” toWe have identified the brain area likely to be responsible for the core, ‘it hurts’, experience of pain” does seem like a bit of a stretch. However the research came from a well-respected research group, led by one of the real heavyweights in brain imaging and pain (Professor Irene Tracey) and the ‘brain’s ouch zone’ became a thing and escaped out into the wilds of the internet.

In response to Segerdahl et al

Later in 2015, things got a little interesting. A different group of eight researchers (including past EP3 2015 speaker Robert Coghill, and future EP3 2016 speaker Gian Domenico Iannetti) published a highly critical paper via F1000Research (an interesting open access science publishing platform that uses an open peer review process). Davis et al (2015) pulled no punches:

“The search for a “pain centre” in the brain has long eluded neuroscientists. Although many regions of the brain have been shown to respond to painful stimuli, all of these regions also respond to other types of salient stimuli. In a recent paper, Segerdahl et al. (Nature Neuroscience, 2015) claims that the dorsal posterior insula (dpIns) is a pain-specific region based on the observation that the magnitude of regional cerebral blood flow (rCBF) fluctuations in the dpIns correlated with the magnitude of evoked pain. However, such a conclusion is, simply, not justified by the experimental evidence provided.” 

The peer reviewers for the Davis et al (2015) response were equally strong in their criticisms of the design, methods, and findings of the original Segendahl et al (2015) paper:

Vania Apkarian (Department of Surgery and Anesthesia, Northwestern University, Chicago, IL, USA):

“Perhaps it would be informative to elaborate on this issue, specifically regarding how an underpowered study can lead into discovering a brain “specific center” for pain perception, the validity of which is doubted by senior scientists in the field.

…Borsook’s commentary on the problems associated with Segerdahl et al. publication is also very astute. He points that [sic] the competition to publish in high end journals pushes the scientist into making more extravagant conclusions than even the author herself or himself actually does not trust. Yet ultimately responsibility rests on the peer review process, and the latter is not guaranteed to be full proof.”

David Borsook (Department of Radiology, Massachusetts General Hospital, Boston, MA, USA):

“At best, the Segerdahal contribution has raised a vibrant discussion in the field, at is worst it is setting the field back not only because of its purported methodological inaccuracy (as evaluated by Davis et al.), lack of acknowledgement of what has come before, perhaps being too enthusiastic about the results and therefore pushing a notion that is unlikely to be true – finding a single brain area that is a pain specific region.”

In response to your response

There’s nothing like a good old fashioned rumble played out in the scientific literature, and Segerdahl and his colleagues (Segerdahl et al 2015response) came out swinging, posting a response to the response, via F1000:

“An interesting and valuable discussion has arisen from our recent article (Segerdahl, Mezue et al., 2015) and we are pleased here to have the opportunity to expand on the various points we made. Equally important, we wish to correct several important misunderstandings that were made by Davis and colleagues that possibly contributed to their concerns about power when assessing our paper…” (emphasis added)

If them’s aren’t fighting words I don’t know what are. Segerdahl et al (2015r) also make the very valid point:

“At no point in the paper do we say that by identifying this ‘fundamental role for the dpIns’ in tracking pain intensity does this mean we’re “promoting the concept of a single spot”, as Davis and colleagues have themselves interpreted from our data. Nor do we ever suggest that the results presented as a Brief Communication should be used to regress back to an expired ‘one region fits all’ pedagogy of where ‘pain is in the brain’. Indeed, that view would be completely contrary to the view and concept about ‘pain representation in the brain’ that we’ve long held and have written extensively about via original studies, reviews and editorials over the past 16 years” [stick that in your pipe and smoke it]. (emphasis and pipe smoking reference, added)

Technical and statistical issues aside, this seems to be a key point – as Segerdahl et al (2015r) point out, the original Segerdahl et al (2015) paper never suggests that the dpIns is ‘the’ pain centre yet, for instance, in his peer review report, Apkarian states:

“the authors make the strong claim that they have identified a single “pain center” in the cortex”

What I find fascinating, is the prospect that Davis et al (2015) and their peer reviewers were not just responding to the Segerdahl et al (2015) paper prima facie, but responding also to the hype in the media and quotes such as “We have identified the brain area likely to be responsible for the core, ‘it hurts’, experience of pain” from Professor Tracey. Fascinating, because it perhaps demonstrates the increasing influence and power of social media and internet reporting not just on the lay public, but on scientists themselves. It also might serve to remind us that scientists are, after all, humans with all of the inherent foibles that make life interesting (looking at the author affiliations and locations, one might begin to wonder if there might be some cross-pond rivalry).

One, okay two, more things

One. The argument is far from over – as recently as 25 January this year, Andre Mouraux (now there is someone who knows how to write a snappy, popular-culture-referencing title for a paper) weighed in on the debate via a comment on the Davis et al (2015) response. You can read his entire comment if you scroll down to the bottom of the document here, but in essence, Mouraux questions the very premise that the dpIns is tracking specific ‘pain intensity’, and suggests that instead it might reflect a broader role for the dpIns in responding to ‘salience’ or ‘stimulation intensity’, severely criticising Segerdahl et al (2015) method for not controlling adequately for this.

Two. If you have the time to read them all, the original paper and subsequent response, the response peer review reports, the comments on the response, the response to the response, and the peer review reports of the response to the response, provide a rich trove of the most current (and critical) thinking from some of the real rockstars of brain and pain research (AD ‘Bud’ Craig is one of the peer reviewers for Segerdahl et al (2015r) and offers an entirely new interpretation of the results).

But are we any closer to an answer to the question “oh pain, where art thou?” Perhaps those looking for answers to where in the brain are looking for pain in all the wrong places, perhaps they have become “brain-bound” and need to look further afield?

To ponder this, here are some smooth sounds from The Soggy Bottom Boys

-Tim Cocks

 

NOIgroup is heading around Australia in 2016 – Townsville, Noosa, Adelaide with details to come on our teaching visits to The Australian Institute of Sport in the Australian Capital Territory, and Perth

15 Responses to “Oh pain, where art thou?”

  1. EG Physio

    http://www.pnas.org/content/108/15/6270.abstract?sid=654c1595-2185-4ae7-ad9a-5e798a859919

    This study indicates strong support for the theory that pain is [quite literally] a thought. Specifically, pain is caused by negative thoughts which have been split off and denied conscious awareness due to their threatening nature.

    The discomfort that these powerful unconscious memories create in the body can be subdued by diversion, nice words and a smile, but never cured this way.

    Reply
    • timcocks0noi

      EG,
      I think that this is a complete misrepresentation of the linked study by Kross et al (2010).

      All Kross et al (2010) have shown is that certain similar brain areas are active when right handed, English speaking individuals, who recently experienced an unwanted romantic relationship break-up, are placed in an fMRI scanner and are either shown pictures of their ex-partners, or have a small patch of their skin heated to a reported painful level.

      In the words of the authors, the study suggests “social rejection and physical pain are similar not only in that they are both distressing, they share a common representation in somatosensory brain systems as well.” There is no support at all in this for the notions that “pain is a thought” or “pain is caused by negative thoughts which have been split off and denied conscious awareness due to their threatening nature”. Further, I think you would be hard pressed to find any up to date scientific evidence for either of these two declarative statements. This seems to be relevant here – http://sebpearce.com/bullshit/, as does this http://journal.sjdm.org/15/15923a/jdm15923a.pdf

      As is quite common in these kinds of studies, there is very little first person data collected – subjects were asked to rate the 15 second pain experience on a scale of 1 very painful – 5 not painful, and also asked to rate “how they felt” when looking at a head-shot picture of their ex-partner on a scale of 1 very bad, to 5 very good. So here we have a complex human experience of romantic relationship breakdown reduced to a five point scale. The subjects reported “distress” when viewing the ex-partner photos, but we don’t don’t know if they also felt sad, angry, rejected, resentful, devastated, depressed, excluded, contemplative, relieved, or any other of the myriad human responses to romantic relationship break-up. A close reading of Kross et al (2010) leads easily to the question of what relevance the similar brain activity between these artificial experiences has at all, especially n light of the original post above and all the associated papers.

      I would encourage others to read the *full* article here (open access): http://www.pnas.org/content/108/15/6270.full to make their own decision.

      Tim Cocks

      Reply
  2. EG Physio

    I think you’re just agrgy about me challenging every other post that appears here. You’re entitled to feel that way.

    But some of these things are not obvious unless you’re actually treating people as a clinician.

    This morning, within a space of 10 minutes, the following happened:

    – patient with weight-bearing pain, every single step at 6/10 intensity.
    – “diagnosis” plantar fascitis
    – tender spot++ in the usual medial/distal calcaneus location
    – pain has been present for weeks
    – within 5 minutes, using guided suggestion, the weight bearing pain reduced to 0/10. Pain on walking was also 0/10. Limp gone.

    The pain relief won’t last longer than a day (that’s my guess – repetition is usually required for lasting relief). But I’d like to see an academic do this, and THEN try to explain what happened using “NOI-approved” science. How about being a bit more open-minded?

    Reply
  3. EG Physio

    Better if I explain that this guided visualization treatment came immediately after a 20 minute ‘usual physio’ intervention which failed completely (pain still 6/10 on walking). So we can rule out empathy as the cause of change which happened later. My confidence level probably changed (since I’m so aware that physical treatments are so weak in effect), and I admit that could be significant.

    I’m never happy letting a client leave without change, so I switched to guided visualization (2 x 5min), wherein significant changes happened, as described.

    Does anyone else use such an approach or am I talking to a brick wall?

    Reply
  4. EG Physio

    There’s hundreds of these videos on Youtube. People see them and think it’s a set up, or that it doesn’t last. Well, I’ve tested it myself (minus the Jesus bit), and I can tell you the pain relief is both real and lasting.

    Pain is indeed a thought. People have absolutely no idea of the power of expectation. Take the blinkers off Physios. Throw the text books away. Try it yourself; you will be stunned.

    Reply
  5. EG Physio

    Consider the guy in the blue hoodie and glasses. Swap the hoodie for a business shirt. Swap the prayer for [insert the name of your special technique – I like Neuro-skeletal-modulation myself]. Swap the street location for an air conditioned office…. and what do you have?

    Legitimacy and expertise. Professionalism.

    You’ll only realize the power of expectation if you do the work (ie. practice, document and recapitulate). You actually have to be prepared to have all your old fashioned superstitions shattered. And you have to be prepared for colleagues to call it new age bullshit and try to humiliate you (like we saw above with Tim’s post).

    The fact is that expectation has been scientifically proven to be as powerful as a clearly analgesic dose of morphine, AND it’s been proven to last just as well as any physical technique ever invented. Most physical treatments studied fail to outperform placebo (just like surgery).

    http://www.ncbi.nlm.nih.gov/pubmed/16150703

    Reply
    • timcocks0noi

      EG
      Seems like the goal posts have moved – from:

      “Specifically, pain is caused by negative thoughts which have been split off and denied conscious awareness due to their threatening nature.”

      On which I called bullshit (the idea – not you), to

      (paraphrasing) ‘Expectation can modulate pain’, a very different proposition, and one for which there is evidence (cited paper above) that *expectations of reduced pain* can reduce the subjective experience of pain.

      But there is also this – http://www.bodyinmind.org/placebo-vs-nocebo/. Note that the research discussed in the post suggests that the pain-reducing expectation effects, in contrast to your reported results, reduce with repetition.

      In contrast to the elicitation of increased pain with suggestion as discussed at BiM, the paper you cite, Koyama et al (2005), also reports “In sharp contrast to the pain modulation evoked by expectations for decreased pain, expectations for increased pain did not significantly alter psychophysical ratings of experienced pain”.

      This suggests that care needs to be taken with blanket phrases such as “the power of expectation” where ‘expectation’ remains an undefined, nebulous idea, and perhaps a more nuanced approach needs to be considered for the role of expectation, rather than suggesting it is a panacea for all aches and hurts.

      Meanwhile the challenge to provide evidence that “pain is (quite literally) a thought” goes unanswered – this is about challenging, is it not?

      Further, I can’t see any link between pain being “caused by negative thoughts split off and denied conscious awareness due to their threatening nature”, and the modulation of pain by expectation. By what proposed mechanism does altering expectation mediate the split off, conscious awareness denied, ‘negative thoughts’?

      The ‘open minded’ argument is nearly always trotted out by advocates of CAM (whether it be acupuncture, Reiki, faith healing – regardless of the attire) as an attempt to close down rational debate, and I would offer the same response in this case – if we are to be ‘open minded’, does that not include an obligation for the one imploring the open mindedness and making the claim to be ‘open minded’ themselves to the possibility that they are wrong? As Richard Feynman said “The first principle is that you must not fool yourself – and you are the easiest person to fool. So you have to be very careful about that”.

      Your anecdote regarding your clinical prowess is interesting – after 20 minutes of ‘usual physio’ in which you have absolute no confidence in (why deliver it ? But that’s another question) and are in fact quite openly hostile about, you switch to something that you passionately believe in, are invested wholly in and even use part of your spare time to write about and argue for, and the patient reports benefit!

      Is it conceivable at all that the same outcome might have been achieved by another practitioner if the beliefs about ‘usual physio’ and ‘guided imagery’ were reversed as was the order of their application? Would this then support the efficacy of ‘usual physio’?

      Why take pot shots at ‘academics’ behind a veil of anonymity, – collect your data and publish your results for peer review – if you are as good as you claim, once the world knows where you are they will beat a path to your door.

      Tim Cocks

      Reply
  6. EG Physio

    I’m not completely anonymous. I’ve met quite a few from NOI, including yourself. A couple of clients has read the stuff I post here.

    “…. if the beliefs about ‘usual physio’ and ‘guided imagery’ were reversed as was the order of their application? Would this then support the efficacy of ‘usual physio’?”

    No, it would support the efficacy of *belief* in ‘usual physio’. There’s not a shred of evidence to support the use of ‘usual physio’. Why do I use it? Because some clients have very rigid mindsets which include the necessity of ‘usual physio’, and to some degree that will dictate what happens.

    I know practitioners who have a huge belief in their physical technique, and of course they get good results. Some people argue that if a practitioner wants to believe in something like spinal mobilization then that’s ok. It’s NOT ok!! Chronic pain is a huge and costly problem, and the profession needs to evolve and find faster and more powerful approaches. Belief in the false makes this impossible. If expectation is all we have, then let’s just face the fact and learn to maximize its effects.

    Many negative thoughts are expectations of continuing difficulty. That’s the connection you were asking about. And by manipulating expectation, you just stop the CNS firing off certain old pathways. When the guy in the video says “I command the pain to leave your neck!”, he is telling the person’s subconscious to just switch off that circuitry… and it does. If you appealed similarly to the conscious mind with: “try to make your neck feel better”, that’s obviously going to fail.

    The part I said about “split off emotions…” I’ll just leave for now. I can’t defend it with evidence, it’s just a theory based on clinical feedback. Hard to describe briefly.

    The most important quote from the Koyama paper that I wanted you to see was this: “Positive expectations (i.e., expectations for decreased pain) produce a reduction in perceived pain (28.4%) that rivals the effects of a clearly analgesic dose of MORPHINE (0.08 mg/kg of body weight, an ˜25% reduction in pain)”.

    But anyone wanting to do this should try it first on non-patients. Even though it’s very simple, it needs practice+++. One other friendly tip: don’t practice on anyone who is heavily invested in you fulfilling certain rigid roles in their life, like receptionsists and colleagues. When they ask for some treatment for their sore back, just do the ‘expected’ mobes and manips. They won’t cope with their pain vanishing in 30 seconds of hand-free treatment when it usually takes 10 minutes of L5 unilateral grade 4 mobilization. They NEED things to stay within certain expectations.

    Worth searching on Youtube: Tom Fisher Street Healing .
    It’s quite possible to do this sort of thing for clients.

    Reply
  7. EG Physio

    In light of the above, we Physios really need to question how it is that a bunch of untrained guys can achieve results that completely eclipse our own. Check out this guy: https://www [dot] youtube [dot] com/watch?v=RXJjLd3XZpE

    Look at it from the clients’ perspective. He may soon have a choice of: multiple 15 minute/$80 consults with a paradigm-locked therapist insisitent on gradual change….OR… some random dude on the street who gets rid of pain almost immediately, and for little or no cost. Sure, you might have to endure a short religious monologue, but you can just tune out to that if you want.

    There are already people who have gone the next step and dropped the God/Jesus references and are achieving similarly spectacular results. The guy I’m thinking of here was studied by a group of doctors in a hospital setting in the US last year. [post your email below if you’d like me to send you the journal ref].

    In the business world, paradigm upheavals such as this are known as ‘disruptive technology’ (think of Airbnb and Uber and how they disrupted the bloated hotel and cab chains). I think we have such a disruption looming on the horizon of the health care industry. A big one.

    The evolution of Physio has been a process of letting go. When the profession decided to grow away from being mere ‘massage therapists’, it immediately looked for something else to cling to. We clung to electrotherapy. When we were ready to let go of electrotherapy, we clung to manual therapies. When it felt safe to let go of manual therapies we started clinging to either chinese needling, Pilates, or a BPS approach. The BPS approach is good in that it recognizes the central importance of the mind, but the techniques tend to lack power in some cases. ‘Scotty, we need more power…’.

    Up until a month ago, I was using hypnosis to treat some chronic pain patients. Now I see that a trance state isn’t actually necessary (some literature had already hinted at this, but there was nothing definitive or solid). Now I’m wondering if I can let go of waking state guided visualizing. I suspect I can. It’s amazing what can be surrendered without affecting outcome.

    I think we’ll end up doing nothing – but it will be a different kind of nothing.

    Reply
  8. EG Physio

    “after 20 minutes of ‘usual physio’ in which you have absolute no confidence in (why deliver it ? But that’s another question) and are in fact quite openly hostile about, you switch to something that you passionately believe in, are invested wholly in and even use part of your spare time to write about and argue for, and the patient reports benefit!”

    Why deliver it? To prove positive expectation is required for healing, obviously! If I have no confidence, that’s equivalent to negative expectation. So by actually doing these clinical experiments regularly, I find out what’s going on. I find out that expectation overrides everything.

    If I had the inclination, I could make the decision to believe in ‘usual physio’, and observe a good outcome that way. But my interest is in believing in belief only, in order to make it as ‘true’ as possible. And then to see how far I can take it. Seeing what can be done to help heal difficult medical conditions is something I’ll attempt to tackle at some point down the track.

    Reply
  9. EG Physio

    Had a client the other day with 2 weeks of elbow pain and stiffness at -20 deg extension and -10 deg flexion. Overuse. House painter.

    During the treatments, this guy was doing something that I found a bit offensive and anti-social. If I’d asked him to stop it might not have been taken too well, so I just let it continue. However it was messing up my concentration and therefore the treatments were ineffective.

    The second treatment was coming to a close and his ROM and pain had still not changed at all since first presenting for help. Finally, I realized I could position him in prone and thereby prevent him doing this thing that I found so annoying. At last I could relax, clear my mind and concentrate. 2 minutes later, “ok show me your elbow range”. Elbow ROM and pain were 60% improved.

    Reply
  10. stephard12

    Thank you for the interesting thoughts, Tim.

    Oh and to the spammer/troll…

    What I see is moving the goalpost, using equivocation, special pleading, anecdotal evidence and denying plausibility.

    You are most likely not up-to-date regarding the science of pain neurophysiology and are certainly not “challenging every post”.

    Reply

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