Prescription Opioids, Morphine and Oxycodone, worsen the severity of chronic pancreatitis altered pain sensitivity and gut microbiome in a caerulein-induced mouse model

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by loss of exocrine/endocrine functions and chronic pain. Opioids such as morphine and oxycodone are widely used for the pain management associated with CP. However, the impact of opioids on the progression of CP has never been evaluated. Therefore, we aim to investigate the impact of opioid use on the severity of CP, pain sensitivity, and gut microbiome in a caerulein-induced CP mouse model. Opioids-treated CP mice showed a distinct clustering of gut microbiome from non-treated CP mice, with preferentially increase in virulent factor and severely compromised the gut barrier. FMT from opioid-treated mice to germ free mice resulted in pancreatic inflammation at suboptimal caerulein dose, while mice received a control microbiome FMT did not show pancreatic inflammation.
Conclusion: Together, these analyses reveal that opioids worsen the severity of CP and induced a significant alteration of the pain sensitivity and gut microbiome in caerulein-induced CP mouse model.