Can pain change our brain maps?

We recently published a paper on the function of the primary somatosensory cortex in Complex Regional Pain Syndrome (CRPS). The primary somatosensory cortex (S1) is a region of the cortex –the outer layer of the brain –which houses a precise and organised map of our body’s surface. Every part of our body surface is represented here by a network or ‘column’ of neurons which is jointly activated when that body part is stimulated.

CRPS is a disorder, usually of the hand or wrist, which is characterised by ongoing pain and dysfunction across several body systems. We don’t know what causes CRPS but it seems that the most common predisposing injury is a common wrist break. Some of the signs and symptoms are altered sensitivity, muscle weakness, and changes in hair and nail growth. Intriguingly, these patients can also have altered perceptions of their affected limb, for instance they often neglect it, or sometimes they perceive it to be bigger than it is in reality.

Using many different neuroimaging technologies, the brain is currently being investigated for its role in CRPS. S1 is one of the regions that is most talked about, given what we know about its role in body representation. Studies have investigated the function of S1 – or more specifically the representation of the CRPS-affected hand in S1 – by stimulating the painful hand (e.g. with light touch or electrical stimulation) and then looking at the S1 activation that results, i.e. the coloured ‘blob’ on the brain scan. Past studies have demonstrated that the S1 area representing the painful part re-organises, in fact the ‘blob’ has been shown to shrink in size. These findings are compelling given the interesting perceptual problems that a lot of CRPS patients have, and these findings have contributed to innovative and non-invasive therapies for CRPS.

That S1 reorganises with pain, and the S1 representation of the CRPS-affected hand is smaller, is widely assumed and accepted. We wanted to know the true state of the evidence; had all the studies come to the same conclusion? We embarked on a systematic review. This involves trawling through the literature to find all the studies that have addressed this question of S1 function in CRPS, pooling their findings and also assessing these studies for their quality. In research this is a great way to get a definitive answer to a specific question.

What did we find? We found consistent evidence that the representation of the CRPS-affected hand in S1 is smaller than that of the unaffected hand, and that of healthy pain-free controls. But the evidence isn’t as strong we thought it would be: we were surprised to find so few studies, recruiting a low total number of subjects, and also a high risk of bias in their findings (namely in the ways they did their statistical analyses and reported their findings).

Our review is important because now we know what’s been investigated and what still needs to be done. We’re not sure what the shrunken hand representation in S1 might mean. We’re not sure if it causes pain or the other way around, or neither of these. But in light of the clinical integration of new therapies that theoretically target this reorganisation in the brain, it’s important that we better understand the brain’s role in CRPS.

Flavia Di Pietro

Flavia Di Pietro 150x150 Can pain change our brain maps?Flavia Di Pietro is a PhD student in the Body and Mind Research Group, Sydney. She is investigating the development of Complex Regional Pain Syndrome (CRPS) after wrist fracture. Specifically, Flavia’s PhD involves brain scanning people who are in a higher than usual amount of pain in the first 3 weeks after the fracture, and then following them for a few months. Her question concerns whether or not there are changes in brain activation patterns that emerge before the CRPS does and if so, what do they tell us about the condition? Flavia is a physiotherapist. She absolutely cleaned up when she did her undergraduate degree at Notre Dame – Brian Edwards Memorial Award, Physio Research Foundation Award, Dean’s Award. No surprises that the Australian Government jumped to support her PhD.  She has spent some time with Dr Giandomenico Iannetti’s lab in London and she is quickly becoming our resident imaging authority. Clearly, she did not write this bio.

Here is Flavia talking more about what she does and a link to her published research.

Reference

Di Pietro F, McAuley JH, Parkitny L, Lotze M, Wand BM, Moseley GL, & Stanton TR (2013). Primary Somatosensory Cortex Function in Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis. Journal of Pain PMID: 23726046

Comments

  1. Thanks Flavia. Very nice paper, and very balanced summary of the current state of affairs.

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  2. stuart miller says:

    Flavia, thanks for all your hard work. Looks like more studies need to be done (with less bias). Do the changes in S1 perpetuate the problem or are they part of the initiation of the syndrome ? I read that they have shown changes in S1 can happen quickly with noxious stimulus (especially with attention to the stimulus). The narrowing between representation of D1 and D5 and between hand and lip in S1 I thought were due to competitive plasticity – with decreased input with profound protective response there is decreased representation which corresponds with perception that limb is perceived to be larger (macrosomatognosia). I thought that this also happened with specific lesions of S1. I still don’t understand why 500mg of vitamin C (anti-oxidant) significantly reduces risk of CRPS post wrist fracture (Zollinger’s study). Just speculating but this would seem to indicate that the initiation of the event may not happen in S1 (unless vitamin C has some effect on plasticity). Please provide perspective. Thanks.

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    Luke Parkitny Reply:

    Hi Stuart:

    The chain of causality is certainly not understood and, I will be brave enough to state, not really researched — YET! There is evidence that peripheral nervous system traffic influences plasticity. There is also evidence that other peripheral events like inflammation/pain induced glial activation influences synaptic function including microglial control over cerebral blood flow.
    As for Zollinger, the studies showed a good effect IF the supplementation occurred almost immediately. There must be something that takes place early after injury that predisposes, at least some people, to CRPS. The time pre-CRPS-diagnosis is completely unexplored except in experimental models. It certainly looks likely that ascorbic acid messes around with the inflammatory response as some studies have shown an impact on inflammatory and oxidative stress biomarkers. It has certainly been trialled in a few conditions (cardiovascular, hepatic, etc) and some positive results have popped out. I am not incredibly familiar with the strength of evidence in these other conditions but, generally speaking, (sorry for this one) more work needs to be done.

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  3. Lesley Singer says:

    Hi
    Very nice subject. I suffer from chronic neuropathic hemi facial pain (petro clival meningioma resection 2000 followed by gamma knife radiotherapy followed by a balloon compression for trigeminal neuralgia . I now have a neuro stim implant on the motor cortex and I believe my S1 to be affected by the way I feel my face is distorted in size and shape on the right and I find I constantly feel my left side is my right (some neglect)? It would be interesting to know what is going on in my S1 but difficult finding out how as there aRE NO STUDIES SINCE THE COHORT WOULD BE VERTY SMALL

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    Danilo Teodoro Reply:

    Just want to say, look for the problem as it, and you can easily help those on pain, but if you don’t you’ll have a hard time finding the solution for the problem I look at it as a muscles problem as explain by Manual of Surgery

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  4. Stuart miller says:

    Danilo, I am not following your comment. Please provide me with better understanding of a ‘muscles problem as explained by Manual of Surgery’ with CRPS. Lesley, I wish you the best of care and await further comments from this discussion for insight. Flavia, I have read that looking for downward causation is chaotic and unpredictable (paraphrased from M Gazzaniga). To ascribe causation to an isolated proximal area seems simplistic with a complex system (perhaps easier to rule out than in and I look forward to ongoing research). I work with a lot of patients post hand / wrist surgeries and I find that there are quite a few with trophic changes, swelling, hyperhidrosis, temperature changes, and ongoing pain but most resolve. Some perceive their limb to be much ‘larger’ than objective findings. Of those, some have fairly immediate relief with mirror presentation (able to make a fist without pain fairly quickly where previously ++ painful) and sometimes, the perception that there is still something ‘wrong’ in the periphery (ie perceived infection, presence of foreign body with neuro-immune response) that leads to signs and symptoms of CRPS – is the neuro-immune response mostly centrally mediated ? It is often the rigid immobilization of the arm (? profound defensive positioning) that goes with it that GMI seems to help as well as lots of support (but I guess this was not supported by clinical studies in Britain). Why does dealing with the results of immobilization (osteopenia) with bisphosphonates (in a recent RCT by Varenna et al, 2012) have such a significant effect ? Looking at all this, I would say that ‘top-down’ processes supplement ‘bottom-up’ processes and motion allows for intermodal integration but finding a pinpoint cause in a complex system is ambitious. I think Lorimer had identified a possible cause (heightened threat) but I don’t know how this presents in the CNS. Good luck and hopefully you can help provide some insight for clinicians and patients ! Please provide perspective.

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