Sensory data-driven classification of complex regional pain syndrome: a multicentre cohort study

Area of Science:

• Neurology
• Pain Medicine
• Sensory Neuroscience

Background:

• Complex regional pain syndrome (CRPS) pathophysiology remains debated, with prior studies proposing 'cold'/'warm' or peripheral/central subtypes.
• Existing research often uses top-down approaches, stratifying patients based on pre-defined mechanisms.

Purpose of the Study:

• To investigate complex regional pain syndrome (CRPS) patients using comprehensive somatosensory testing.
• To identify potential patient subgroups through unbiased statistical methods, diverging from previous top-down strategies.

Main Methods:

• Quantitative Sensory Testing (QST) was performed on 604 CRPS patients (type I and II) following the German Research Network on Neuropathic Pain (DFNS) protocol.
• A hypothesis-free cluster analysis was applied to a training set (n=380) and validated on a separate set (n=224).
• Thirteen sensory parameters, including thermal and mechanical detection and pain thresholds, were assessed to define individual sensory profiles.

Main Results:

• Three distinct sensory phenotypes were consistently identified across the training and validation sets.
• The largest phenotype (n=382) exhibited hypersensitivity to cold and heat.
• A second phenotype (n=200) showed sensory loss (thermal and mechanical), while a third (n=22) presented with allodynia and mechanical hyperalgesia.

Conclusions:

• A novel bottom-up approach successfully stratified CRPS patients based on objective sensory phenotypes.
• This stratification enhances mechanistic understanding of CRPS.
• Comparative analysis with human pain surrogate models provides further insights into CRPS pathophysiology.