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Papers of the Week

Papers: 6 May 2023 - 12 May 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology

Acute Pain

2023 Apr 28



Gut microbiota and metabolites drive chronic sickle cell disease pain.


Sadler KE, Atkinson SN, Ehlers VL, Waltz TB, Hayward M, Rodríguez García DM, Salzman NH, Stucky CL, Brandow AM


Pain is a debilitating symptom and leading reason for hospitalization of individuals with sickle cell disease. Chronic sickle cell pain is poorly managed because the biological basis is not fully understood. Using transgenic sickle cell mice and fecal material transplant, we determined that the gut microbiome drives persistent sickle cell pain. In parallel patient and mouse analyses, we identified bilirubin as one metabolite that induces sickle cell pain by altering vagus nerve activity. Furthermore, we determined that decreased abundance of the gut bacteria is a critical driver of chronic sickle cell pain. These experiments demonstrate that the sickle cell gut microbiome drives chronic widespread pain and identify bacterial species and metabolites that should be targeted for chronic sickle cell disease pain management.