Cortical reorganization of the healthy hand in upper-limb complex regional pain syndrome(CRPS): Is reorganizations of common beliefs about CRPS necessary?
-
Stephen Butler
In this issue of the Scandinavian Journal of Pain, Di Pietro et al. [1] report some interesting findings concerning reorganization of the somatosensory cerebral cortex (S1) in subjects with chronic pain and having the diagnosis of complex regional pain syndrome (CRPS). The use of fMRI and PET to try to unravel central function or dysfunction, both as the cause and/or effect of chronic pain is a burgeoning field. We welcome more information that can help shed light on this area in patients using non-invasive investigation of brain function. CRPS continues to be poorly understood and with poor treatment outcomes despite the use of a wide spectrum of treatment modalities. Even though this is a small patient segment, it deserves more attention from researchers, both clinical and in the basic sciences.
1 Mini-review of diagnosis and treatment of CRPS
Loss of function is common in CRPS. Abnormal sensory and motor findings are also common and form the basis for making the diagnosis of CRPS [2]. Despite much interest and ongoing research, even using animal models, CRPS is poorly understood. Various treatment strategies have been reported but a subset of patients fail to respond to a wide variety of treatments including invasive (spinal cord stimulation), pharmacological (topical, oral, intravenous, intra-spinal) and cognitive/behaviorally based rehabilitation or a combination all of these. In the past, the focus was on the periphery as demonstrated by the older term for CRPS: “reflex sympathetic dystrophy”. This term fell into disuse when it became apparent that not all with the diagnosis demonstrated abnormalities related to the sympathetic nervous system. The focus recently has been more and more on central processes and the article by Di Pietro et al. is part of this newer area of study.
Why the “negative” findings by Di Pietro [1] are important: Contrary to “accepted beliefs”, S1 of the CRPS limb is not decreased but S1 of the healthy limb is increased.
At first glance, one might say “Ho hum, just another negative study” but there is much more here. To fully understand the findings, one needs to read the original article that is the basis for this research [3]. The background for the previous article was a review by Di Pietro et al. of research supporting the commonly accepted view that imaging or other studies by whatever method shows that the S1 cortex with input from the affected limb has a smaller representation of that limb than does the S1 cortex receiving input from the healthy limb [4]. That review identified methodological errors in many studies and prompted the Di Pietro team to check those findings with fMRI in a more rigorous study.
2 Changes in S1 not related to duration of CRPS, nor to compensatory use of healthy limb
To their surprise, the S1 cortex representation of CRPS limbs (hands) was not decreased but that of the healthy limbs (hands) in CRPS subjects was enlarged! These findings go against the common understanding which is that patients with CRPS undergo shrinkage of the primary somatosensory cortex that is supposedly due to decreased or loss of use of the extremity involved. Di Pietro et al. then went back to their data from the first study with the idea that the enlargement of the S1 region on the healthy side was due to a compensational increase in activity of the healthy limb. This theory is supported by some data from post stroke studies [5] where the increase in the primary motor cortex subserving the healthy side is felt to be maladaptive and interferes with rehabilitation. Could this also be the case in CRPS?
Di Pietro et al. also felt that the duration of CRPS and a longer duration of increased use of the healthy limb would correlate with the increase in the S1 cortical representation. It seemed so logical. But no, they found no correlation between CRPS limb decreased function, healthy limb increased function nor duration of CRPS and the increase in the S1 representation of the limb (hand) on the healthy side. This is a little disturbing and will upset many since much research and treatment of CRPS is based on the idea that a decrease in S1 cortical function is due to decreased use of the affected limb and compensatory increased use of the healthy limb.
3 Other implications: motor cortex (M1) changes in CRPS should be re-evaluated
Although not the focus of this article, there is also imaging evidence of decreased motor cortex (M1) representation of the affected limb in CRPS which is also the basis for active physiotherapy as an important component of treatment for CRPS. It is possible that the same misinterpretation of imaging data applies to this concept. This suggests that more rigorous studies of the M1 area in CRPS subjects (both the affected and the healthy sides) and in normal volunteers be done in the same manner as Di Pietro et al. have done.
4 Criticisms of Di Pietro et al. [1]
However, going back to the original article, several questions must be raised. The first is that Di Pietro et al. re-evaluated the diagnosis of CRPS in the 12 subjects that were included in the study but only 7 fulfilled the accepted Budapest criteria [2]. Could it be that the others had another mechanism to account for their symptoms and therefore the cohort may not have a restricted phenotype felt typical of CRPS? Given what is known about CRPS, this is unlikely and where in that diagnostic paradigm patients change from limb pain to CRPS is not known.
Those subjects also had many other pain problems. Could this have affected the outcome? Again, it is unlikely since few patients with CRPS have only focal pain.
And then there is the problem of sufficient subject numbers for statistical significance. The experts in PET say that significance is assured if a study has at least 9 subjects and it is likely that the same applies to fMRI which has slightly better resolution. In the previous study, Di Pietro et al. looked at this issue. They have the expertise and have carefully documented the effect size and other issues related to statistical significance.
5 Conclusion and implications
This, and the previous study by Di Pietro are very interesting and controversial since they present proof that long held ideas about CRPS may be false. There will be many sceptics and disbelievers who will not accept this information. Therefore, the next step is to repeat the study in another research group using the same protocol to see if these new findings can be replicated. A corollary is to also rethink the issues surrounding the motor cortex data in CRPS. Perhaps there are also surprises there as well.
DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2016.06.004.
-
Conflicts of interest: None declared.
References
[1] Di Pietro F, Stanton TR, Moseley GL, Lotze M, McAuley JH. An exploration into the cortical reorganisation of the healthy hand in upper-limb complex regional pain syndrome. Scand J Pain 2016;13:18–24.Search in Google Scholar
[2] Hardin RN, Bruehl S, Stanton-Hicks M, Wilson PR. Proposed new diagnostic criteria for complex regional pain syndrome. Pain 2007;124:184–9.Search in Google Scholar
[3] Di Pietro F, Stanton TR, Moseley GL, Lotze M, McCauley JH. Interhemispheric somatosensory differences in chronic pain reflect abnormality of the healthy side. Hum Brain Mapp 2015;36:508–18.Search in Google Scholar
[4] Di Pietro F, McCauley JH, Parkitny L, Lotze M, Wand BM, Moseley GL, Stanton TR. Primary somatosensory cortex function in complex regional pain syndrome: a systematic review and meta-analysis. J Pain 2013;14:1001–18.Search in Google Scholar
[5] Manganotti P, Acler M, Zanette ZP, Smania N, Fiaschi A. Motor cortex disinhibition during early and late recovery after stroke. Neurorehabil Neural Repair 2008;22:396–403.Search in Google Scholar
© 2016 Scandinavian Association for the Study of Pain
Articles in the same Issue
- Scandinavian Journal of Pain
- Editorial comment
- Increased deep pain sensitivity in persistent musculoskeletal pain but not in other musculoskeletal pain states
- Clinical pain research
- Increased deep pain sensitivity in persistent musculoskeletal pain but not in other musculoskeletal pain states
- Editorial comment
- Patient Reported Outcomes (PROs) are sensitive outcome-variables in patients with chronic pain: Importance of self-efficacy
- Observational study
- Using patient reported outcomes in oncology clinical practice
- Editorial comment
- Cortical reorganization of the healthy hand in upper-limb complex regional pain syndrome(CRPS): Is reorganizations of common beliefs about CRPS necessary?
- Original experimental
- An exploration into the cortical reorganisation of the healthy hand inupper-limb complex regional pain syndrome
- Editorial comment
- Is there hope for the most complicated chronic pain patients facing back surgery?
- Educational case report
- A preoperative interdisciplinary biopsychosocial opioid reduction program in patients on chronic opioid analgesia prior to spine surgery: A preliminary report and case series
- Editorial comment
- Pain management in the Emergency Department – Still a long way to go?
- Clinical pain research
- Mandatory documentation of pain in the emergency department increases analgesic administration but does not improve patients’ satisfaction of pain management
- Editorial comment
- Pain relief during childbirth: Efficacy and safety of prolonging labour-analgesia with morphine directly into the lumbar cerebro-spinal-fluid (CSF)
- Systematic review
- Prolonging the duration of single-shot intrathecal labour analgesia with morphine: A systematic review
- Editorial comment
- The intricate relationship amongst pain intensity, fear and avoidance
- Systematic review
- A meta-analysis of fear-avoidance and pain intensity: The paradox of chronic pain
- Editorial comment
- Local infiltration analgesia(LIA), risk of local anaesthetic systemic toxicity (LAST) and kidney failure from NSAID in elderly patients
- Topical review
- Local infiltration analgesia in knee and hip arthroplasty efficacy and safety
- Editorial comment
- Analysis of pain-intensity measurements
- Topical review
- How to analyze the Visual Analogue Scale: Myths, truths and clinical relevance
- Editorial comment
- The relationship between chronic pain and cardiovascular disease: Squaring the circle?
- Systematic review
- Assessing the relationship between chronic pain and cardiovasculardisease: A systematic review and meta-analysis
- Editorial comment
- Optimists fare better when chronic pain strikes – Or does pain related disability make us pessimists?
- Observational study
- Constructs of health belief and disabling distal upper limb pain
- Editorial comment
- Attitude and belief of pain-therapists are important when trying to help chronic pain patients: The Norwegian version of the Pain Attitudes and Beliefs Scale (PABS) improved by Rasch analysis
- Observational study
- Rasch analysis resulted in an improved Norwegian version of the Pain Attitudes and Beliefs Scale(PABS)
- Editorial comment
- Anxiety could play a larger role than depression in migraine headache
- Clinical pain research
- The relative importance of anxiety and depression in pain impact in individuals with migraine headaches
- Editorial comment
- Bringing the lab to the people: Experimental pain testing in the general population
- Clinical pain research
- Pressure and cold pain threshold reference values in a large, young adult, pain-free population
- Editorial comment
- Improving pain treatment in children
- Clinical pain research
- A randomized controlled trial of amitriptyline versus gabapentin for complex regional pain syndrome type I and neuropathic pain in children
- Editorial comment
- Gut gateway to generalized pain
- Original experimental
- A low fermentable oligo-di-mono saccharides and polyols(FODMAP) diet reduced pain and improve ddaily life in fibromyalgia patients
- Editorial comment
- Measuring outcomes of pain management
- Clinical pain research
- Osteoarthritis patients with pain improvement are highly likely to also have improved quality of life and functioning. A post hoc analysis of a clinical trial
- Clinical pain research
- Construct validity and reliability of Finnish version of Örebro Musculoskeletal Pain Screening Questionnaire
- Observational study
- Total sleep deprivation and pain perception during cold noxious stimuli in humans
- Corrigendum
- Corrigendum to ‘Reliability of pressure pain threshold testing in healthy pain free young adults’ [Scand. J. Pain 9 (2015) 38–41]
Articles in the same Issue
- Scandinavian Journal of Pain
- Editorial comment
- Increased deep pain sensitivity in persistent musculoskeletal pain but not in other musculoskeletal pain states
- Clinical pain research
- Increased deep pain sensitivity in persistent musculoskeletal pain but not in other musculoskeletal pain states
- Editorial comment
- Patient Reported Outcomes (PROs) are sensitive outcome-variables in patients with chronic pain: Importance of self-efficacy
- Observational study
- Using patient reported outcomes in oncology clinical practice
- Editorial comment
- Cortical reorganization of the healthy hand in upper-limb complex regional pain syndrome(CRPS): Is reorganizations of common beliefs about CRPS necessary?
- Original experimental
- An exploration into the cortical reorganisation of the healthy hand inupper-limb complex regional pain syndrome
- Editorial comment
- Is there hope for the most complicated chronic pain patients facing back surgery?
- Educational case report
- A preoperative interdisciplinary biopsychosocial opioid reduction program in patients on chronic opioid analgesia prior to spine surgery: A preliminary report and case series
- Editorial comment
- Pain management in the Emergency Department – Still a long way to go?
- Clinical pain research
- Mandatory documentation of pain in the emergency department increases analgesic administration but does not improve patients’ satisfaction of pain management
- Editorial comment
- Pain relief during childbirth: Efficacy and safety of prolonging labour-analgesia with morphine directly into the lumbar cerebro-spinal-fluid (CSF)
- Systematic review
- Prolonging the duration of single-shot intrathecal labour analgesia with morphine: A systematic review
- Editorial comment
- The intricate relationship amongst pain intensity, fear and avoidance
- Systematic review
- A meta-analysis of fear-avoidance and pain intensity: The paradox of chronic pain
- Editorial comment
- Local infiltration analgesia(LIA), risk of local anaesthetic systemic toxicity (LAST) and kidney failure from NSAID in elderly patients
- Topical review
- Local infiltration analgesia in knee and hip arthroplasty efficacy and safety
- Editorial comment
- Analysis of pain-intensity measurements
- Topical review
- How to analyze the Visual Analogue Scale: Myths, truths and clinical relevance
- Editorial comment
- The relationship between chronic pain and cardiovascular disease: Squaring the circle?
- Systematic review
- Assessing the relationship between chronic pain and cardiovasculardisease: A systematic review and meta-analysis
- Editorial comment
- Optimists fare better when chronic pain strikes – Or does pain related disability make us pessimists?
- Observational study
- Constructs of health belief and disabling distal upper limb pain
- Editorial comment
- Attitude and belief of pain-therapists are important when trying to help chronic pain patients: The Norwegian version of the Pain Attitudes and Beliefs Scale (PABS) improved by Rasch analysis
- Observational study
- Rasch analysis resulted in an improved Norwegian version of the Pain Attitudes and Beliefs Scale(PABS)
- Editorial comment
- Anxiety could play a larger role than depression in migraine headache
- Clinical pain research
- The relative importance of anxiety and depression in pain impact in individuals with migraine headaches
- Editorial comment
- Bringing the lab to the people: Experimental pain testing in the general population
- Clinical pain research
- Pressure and cold pain threshold reference values in a large, young adult, pain-free population
- Editorial comment
- Improving pain treatment in children
- Clinical pain research
- A randomized controlled trial of amitriptyline versus gabapentin for complex regional pain syndrome type I and neuropathic pain in children
- Editorial comment
- Gut gateway to generalized pain
- Original experimental
- A low fermentable oligo-di-mono saccharides and polyols(FODMAP) diet reduced pain and improve ddaily life in fibromyalgia patients
- Editorial comment
- Measuring outcomes of pain management
- Clinical pain research
- Osteoarthritis patients with pain improvement are highly likely to also have improved quality of life and functioning. A post hoc analysis of a clinical trial
- Clinical pain research
- Construct validity and reliability of Finnish version of Örebro Musculoskeletal Pain Screening Questionnaire
- Observational study
- Total sleep deprivation and pain perception during cold noxious stimuli in humans
- Corrigendum
- Corrigendum to ‘Reliability of pressure pain threshold testing in healthy pain free young adults’ [Scand. J. Pain 9 (2015) 38–41]
