Chronic pain and complex regional pain syndrome are associated with alterations to the intestinal microbiota in both humans and mice. An observational cross-sectional study

Objective: This study aimed to evaluate pain metrics and gut microbiota differences from human subjects with complex regional pain syndrome (CRPS) compared to cohabitants (HHC) and non-cohabitating (biobank) controls. In addition, we aimed evaluate longitudinal changes of gut microbiota using a mouse model of acute and chronic CRPS. Methods: In an observational, cross-sectional study, 25 patients with CRPS and 24 household controls (HHC) were recruited, completed pain questionnaires, and submitted stool samples. 23 biobank stool samples were matched to the CRPS group. Additionally, longitudinal stool samples were collected from a mouse model of acute and chronic CRPS. 16S rRNA gene sequencing analysis was performed on all samples. Results: A diagnosis of CRPS is associated with higher pain, increased pain interference, and decreased physical and social function when compared to HHC. Interestingly, 46% of HHC reported significant daily pain. In the households where HHC were also suffering from pain, there was decreased bacterial richness and diversity when compared to households wherein only the participant with CRPS suffered from pain. Furthermore, when comparing households where the HHC had significant pain, CRPS was clinically more severe. In the mouse model of CRPS, we observed decreased bacterial richness and diversity when compared to non-cohabitating littermate controls. Conclusions: Both humans living in chronic pain households and mice shared distinct taxa over the time course of disease and pain chronicity. These findings suggest that microbiota changes seen in CRPS as well as in a mouse model of CRPS may reflect pain chronicity and may indicate that pain alone can contribute to microbiota dysbiosis. The trial was registered at ClinicalTrials.gov (NCT03612193).