Primary Motor Cortex Function in Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis

Dysfunction in the central nervous systemis thought to underlie themovement disorders that commonly occur in complex regional pain syndrome (CRPS), with much of the literature focusing on reorganization of the primary motor cortex (M1). Presumed changes in the M1 representation of the CRPS-affected body part have contributed to new CRPS treatments, which are increasingly being integrated in the clinic. We systematically investigated the evidence for altered M1 function in CRPS. We adhered to rigorous systematic review procedure in our search strategy, risk-of-bias appraisal, and data extraction. Eighteen studies comprising 14 unique data sets were included. The included studies used several neuroimaging techniques, whose outcomeswe grouped intoM1 cortical excitability, spatial representation, reactivity, and glucose metabolism, and conducted meta-analyses where possible. Risk of bias across studies was high, mainly due tomissing data and unblinded assessment of outcomes. No definitive conclusions can be drawn regarding M1 spatial representation, reactivity, or glucose metabolism in CRPS. There is limited evidence for bilateralM1 disinhibition in CRPS of the upper limb. Perspective: Despite widely held assumptions of primary motor cortex dysfunction in complex regional pain syndrome, there is only evidence to support bilateral disinhibition, and there is high risk of bias across the literature. Refereed/Peer-reviewed