Acute inflammation and risk factors for complex regional pain syndrome

Abstract

An aberrant immune response to injury has been implicated in the pathogenesis of complex regional pain syndrome (CRPS). However, there has been very little investigation of the normal response to injury, and no investigation of the potential relationship between acute inflammation after injury and the known risk factors for CRPS. The central aim of this thesis was to address this gap, thereby facilitating the investigation of the role of acute inflammation in the subsequent development of CRPS. Study 1 used a systematic review and meta-analysis to identify the immune markers associated with CRPS. Study 2 applied Rasch analysis to examine the psychometric properties of the Depression Anxiety and Stress Scales (DASS-21), the most suitable tool for a subsequent study, but one that has not been fully tested. Study 3 was an experiment designed to measure the effect of blood sample type and thaw-freeze cycles on cytokine concentrations. Study 4 replicated the sampling and analysis methods of Study 3, in a cross-sectional study of 240 blood samples, to characterise inflammation in the first 28 days after a fracture. Study 5 was a cross-sectional study designed to investigate the relationships between acute inflammation after a fracture and the risk factors for the development of CRPS. This thesis showed that established CRPS is associated with a pro-inflammatory cytokine balance and revealed new information about different inflammatory profiles that are associated with different durations of the disorder. By applying best practice methods, based on the outcomes of Studies 2 and 3, this thesis showed that in the acute post-fracture stage, the chemokines IP-10 and eotaxin are associated with pain intensity, which is reported to be the strongest predictor of who will develop CRPS. By characterising the normal response to a fracture, the most common risk factor for CRPS, and relating it to other risk factors for CRPS, the current thesis provides the critical platform from which to investigate the relationship between acute stage inflammation and the subsequent development of CRPS.