Complex regional pain syndrome is associated with time-dependent alterations to the intestinal microbiota in both humans and mice

Chronic complex regional pain syndrome (CRPS) is both devastating and life-changing for those afflicted. We do not yet understand why patients with an acute injury will develop CRPS, nor is it clear how patients with acute CRPS transition to chronic CRPS. Previous work has demonstrated that changes in the gut microbiome are associated with a diagnosis of chronic CRPS, but, whether the microbiome contributes in a causative fashion to CRPS pain chronification remains unknown. For the first time, we examined the gut microbiota in both acute and chronic CRPS using both human samples as well as a longitudinal mouse CRPS model. Community composition differences, including a decreased ratio of Firmicutes to Bacteroidetes and enhanced abundances of biomarker taxa such as Sutterella and Alloprevotella are apparent in subjects with CRPS in comparison to healthy, non-cohabitating matched controls. Similarly, we observed changes in bacterial richness, Shannon diversity and community taxonomic composition in a mouse model of chronic CRPS, when compared to littermate controls. Similar to our observations in humans, mice with both acute and, chronic CRPS exhibit dysbiosis, evidened by a decreased ratio of Firmicutes to Bacteroidetes, but with emergence of distinct biomarkers over the timecourse of disease.. This work demonstrates that microbiota changes seen in human CRPS as well as in a mouse-model of CRPS reflect pain chronicity, and that pain and injury alone can cause dysbiosis of gut microbiota. Identificiation of CRPS biomarkers may facilitate changes in clinical practice and/or the development of new therapeutics approaches to prevent pain chronification.