S-ketamine alleviates morphine-induced hyperalgesia via decreasing the gut Enterobacteriaceae levels: Comparison with R-ketamine.
Neuroscience March 5, 2025 Hanyu Liu, Siqi Yang, Qi Zhang et al.
Opioid-induced hyperalgesia (OIH) is a complication of pain treatment where opioids paradoxically increase pain sensitivity. Using a mouse model, about 60% of mice developed OIH after three days of morphine, shown by abnormal movement and anxiety-like behaviors. Mice whose gut microbiota were eliminated with antibiotics did not develop hyperalgesia, but those receiving fecal transplants from OIH mice did. S-ketamine, but not R-ketamine, prevented OIH. Gut microbiota analysis revealed increased Enterobacteriaceae in OIH-susceptible mice, which decreased after S-ketamine treatment. The findings suggest S-ketamine alleviates morphine-induced OIH by reducing gut Enterobacteriaceae levels.