Bifidobacterium pseudolongum attenuates morphine tolerance via TLR4 in a male mouse model of bone cancer pain.

Abstract

Previous studies have indicated the involvement of gut microbiota in the development of morphine tolerance. However, it remains unclear whether the gut microbiota plays a role in the development of morphine tolerance in the context of bone cancer pain (BCP). Here, we established a male mouse model of morphine tolerance concomitant with BCP and investigated the changes in gut microbiota and Toll-like receptor 4 (TLR4) expression in the ipsilateral spinal cord to the tumor implantation side. We observed significant alterations in gut microbiota accompanied by upregulation of spinal TLR4 expression after long-term morphine administration in BCP mice. Antibiotic-mediated gut microbiota depletion and Bifidobacterium pseudolongum (B.pseudolongum) administration both effectively attenuated morphine tolerance development in BCP mice and reduced spinal TLR4 overexpression. Plasma metabolites changed after formation of morphine tolerance in BCP mice. Our findings offer new insights into the prevention and treatment of morphine tolerance in BCP mice, suggesting that B. pseudolongum may serve as an effective therapeutic strategy.