Aug 7

Clinically Significant Subsets of CRPS

1 comment


We’d like to open a forum discussion about the identification, and ultimately treatment of clinically significant subsets of CRPS. This forum proposes some example empirical subsets, and is meant to initiate and stimulate forum discussion concerning this topic which will be discussed in detail in Valencia.

CRPS is a heterogeneous disease and it is generally agreed that there are likely several mechanisms at play. If that is the case, it is unlikely that any particular intervention (e.g. pharmaceutical) would be able to demonstrate statistical significance with the small sample sizes typically available to study this ‘rare disorder’ (< 200K in US, per FDA).

Showing significant clinical improvement to a pragmatic intervention in a specific sub-set of CRPS patients (as defined by quantifiable mechanisms or clinical features) would be ideal. This will require different designs, sample selection criteria, and modern statistical analysis (e.g. Hierarchical Linear Modeling).

To achieve the goal above, we will need to empirically identify coherent, treatable subsets; explore potential underlying mechanisms that can be (more) objectively identified; and empirically identify systematized treatments for those specific targets. Funding will need to be obtained to develop the methodology for and conduct studies to achieve these aims.

Potential Clinically Significant Subsets

Warm CRPS Subset (e.g., defined by mechanisms, such as inflammation or sympathoplegia/small fiber neuropathy, clinical features believed to relate to mechanisms, etc.) Cold CRPS Subset (defined by mechanisms such as sympathetic hyperactivity, adrenergic receptor upregulation in periphery, clinical features believed to relate to mechanisms, etc).

Abnormal response to triple phase Bone Scan (e.g responsive to bisphosphonates)

Pronounced Affective Diseases

Specific Etiologies

Central Sensitization

Peripheral Sensitization

and of course the four statistically derived subsets (from Budapest factor/cluster analysis)

High pain report (allodynia, hyperalgesia)

Vasomotor (as above, warm and cold)


Trophic/Dystrophic/Motoric (dystonic, myoclonic, weakness etc)


Thoughts? Please help us develop these concepts in this forum. Recall that the first consideration is proper identification of the subset, preferably using objective/quasi-objective measures (that can later be used to test treatment of the subsets. We will also need to consider putative mechanisms so as to develop logical empirical treatments.


Harden and Bruehl

A couple of thoughts:

I wonder if body dysmorphia is another clinically important subset. While challenging to objectively measure, clinically this group need a specific pathway of rehabilitation management to see progress in the form of pain reduction and increased functional activity.


Some of my work has focused on improving objective ways of measuring allodynia and skin temperature asymmetries, because I think those are also important subsets. I would argue (and do in our paper in Can J Pain) that some previous work in temperature asymmetries use flawed methodology, and this needs to be addressed moving forward.






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