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Hard to ignore

By Timothy Cocks Philosophy of pain 10 May 2017

It’s only two pages, and it’s available to everyone here, but this little Letter in JAMA Neurology from June last year is a striking read

The “Pain Matrix” in Pain-Free Individuals

Activation of this so called pain matrix or pain signature has been related to perceived pain intensity, both within and between individuals and is now considered a candidate biomarker for pain in medico-legal settings and a tool for drug discovery. The pain specific interpretation of such functional magnetic resonance imaging (fMRI) responses, although logically flawed remains pervasive. For example, a 2015 review states that “the most likely interpretation of activity in the pain matrix seems to be pain.”

In this study, we administered noxious mechanical stimuli to individuals with congenital insensitivity to pain and sampled their brain activity with fMRI

Strikingly, fMRI revealed normal activation of brain regions commonly activated by painful stimuli in both pain-free individuals (Figure, A and C). There was no significant difference between patients and control individuals either across the entire pain matrix or in key pain matrix regions. (emphasis added)

 What do we make of this? (Cue raging debate in comments)

-Tim Cocks


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  1. jqu33431quintner

    I have always suspected that “pain matrix” is a misnomer.

    1. Thanks John
      As Iannetti and Mouraux point out in the classic 2010 paper, Melzack’s ‘Neuromatrix’ was never intended as a specific anatomical substrate of pain:

      “the term ‘‘Pain Matrix’’ is currently used in a sense very different from its initial conception. As a matter of fact, the Neuromatrix was originally proposed because researchers had failed to identify spatially segregated cortical regions specifically devoted to the perception of pain. Most importantly, the function of the Neuromatrix was not restricted to the perception of pain, which was considered to be only one of its many possible perceptual outputs. Accordingly, the Neuromatrix was described as a widespread ensemble of neurons integrating various sources of input, both nociceptive and non-nociceptive, in a Hebbian fashion. In other words, in its original definition, the Neuromatrix was certainly not pain specific: ‘‘the neuromatrix, distributed throughout many areas of the brain, comprises a widespread network of neurons that generates patterns, processes information that flows through it and ultimately produces the pattern that is felt as a whole body possessing a sense of self’’
      ‘From the neuromatrix to the pain matrix (and back)’

      Notwithstanding this, and the significant work that Melzack’s neuromatrix theory has done, Melzack never did offer an explanation of just how this bit worked “the sentient neural hub, which converts (transduces) the flow of neurosignatures into the flow of awareness” ( I’ve long thought that Melzack got a free pass on the whole ‘sentient neural hub’ thing…

      My best

  2. Lars Avemarie

    There is problems with the paper, if we are trying to draw conclutions on the basics of a papers (on patients with congenital insensitivity), and state that that in any way is the same as people without this very rare and specific diagnosis.

    No, the matrix is not dead, the paper only show that activation of the matrix in people that can’t feel pain, they don’t feel pain, when the matrix is activated.

    We can’t compare people with congenital insensitivity, to “normal” people without this very rare and specific diagnosis.

    1. Tim Salomons

      The aim here wasn’t really to characterise pain responses in either group, as much as to demonstrate that when we see an activated pain matrix we cannot assume that an individual is experiencing pain. In other words, the pain matrix is not sufficient evidence of pain. Findings in healthy subjects (by Mouraux and Iannetti, Downar and Davis etc.) corroborate this finding. As Beccah says below, the best way to know if someone is in pain is still to ask them!

      1. Hi Tim, really appreciate you taking the time to stop by and comment.

        It’s been said that science shouldn’t be reduced to t-shirt slogans, but I’m thinking of getting a few printed with “The pain matrix is not sufficient evidence of pain” in big bold letters!!

        My thanks and very best

    2. Hi Lars, thanks for taking the time to comment.
      What conclusion would you draw from this “activation of the matrix in people that can’t feel pain, they don’t feel pain, when the matrix is activated”?

      My best, Tim

  3. Beccah

    I agree that an individual with a congenital insensitivity is not a marker for “normal”, but if we step back and examine the big picture, we may recognize that a neurotag activation DOES NOT HAVE TO result in pain. Is that not what we are hoping for when we teach patients to learn to move with less pain. The movement is the same, we are teaching the brain not to protect with pain during safe movement. Why would the bulk of the neurotag change in that case? The credible evidence of danger, the memories of past experiences, the scary things they have heard from their previous medical providers are all still present, only now the patient is using “heavier” credible evidence of safety to “outweigh” the danger that is present.

    To me, it makes sense and supports our case that the brain can, in fact, be retrained to know the difference between safe movement and dangerous movement.

    1. Hi Beccah
      Welcome to NOIjam, thanks for stopping by. I think you’ve summed it up nicely with the idea of the bigger picture (as does the paper’s lead author) and your further comment about asking the person.

      For me this paper does a number of things – it says thanks and acknowledges the groundbreaking work in brain imaging and pain and the theories that came from these. But, it also challenges the very same theories and demands careful thought about the complex human experience that is pain, lest we fall prey to neuroreductionist, simplistic thinking.
      My best

  4. Beccah

    sorry, one more thing: this further proves that we cannot look at an image to determine how a patient is feeling. In order to know, we must ask them

  5. davidbutler0noi

    Thanks Tim,

    Those of us giving pain related courses, subjects and presentations need to be aware of continued challenges to notions of pain neurosignatures. I still use neuromatrix as paradigm – certainly wider and more encompasssing than the previous dominating paradigm of gate control theory. I talk about pain neurotags (schemas, representations, neurosignatures etc) and always reinforce that they are more process like rather than entity like and that many other “things” such as loud noise would resemble a pain neurotag in the brain.

    The paradigm gave us the precious notion of distributed processing and hence an increased awareness of the power of context. But I do wonder as I teach, if a Kuhnian style crisis is emerging and if we will still be using similar language and paradigms in say 5 years, and if our current paradigms are reasonable and fair for the present .


    1. Hi David, this raises an important point. People often confuse Melzack’s original “neuromatrix” with the “pain matrix”. The former is a theory of representation that you correctly identify as a process rather than a specific piece of anatomical geography. The latter is a map of neural activation that is almost always observed in neuroimaging studies. Findings like ours and those of Mouraux, Downar etc. suggest that the pain matrix is not specific to pain but don’t have anything to say about the neuromatrix construct. If I recall my Melzack correctly, he didn’t say anything at all about a requirement that any particular part of the neuromatrix be specific to pain, just that pain is an emergent property of the matrix.

      1. davidbutler0noi

        Thanks Tim – I am scuttling back to Melzack too!


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