Purpose: To determine the influence of miR-140-5p on morphine tolerance in rats.Methods: Sprague-Dawley (SD) rats were randomly divided into morphine tolerance (MT) and saline control (NS) groups, respectively. Rats in MT group were injected with 10 μL (10 μg) morphine twice daily for seven consecutive days while those in NS group were administered the equivalent volume of normal saline. The maximum effect of morphine (MPE) was computed from tail-flick test results. MiR-140-5p mimics and

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... ke receptor 4 (TLR4) lentivirus were transfected separately or co-transfected into model rats. MiR-140-5p and TLR4 expression were determined by quantitative real-time polymerase chain reaction (RT-qPCR) or western blotting. Dual-luciferase reporter assay was used to verify the target relationship between miR-140-5p and TLR4.Results: The expression of miR-140-5p was decreased, while the expression of TLR4 increased in morphine-tolerant rats (p < 0.05). TLR4 was a target of miR-140-5p. At 24 and 48 h after injection, MPE clearly increased and TLR4 expression was reduced under miR-140-5p overexpression or TLR4 knockdown (p < 0.05). Moreover, there were no significant changes in MPE or levels of TLR4 when miR-140-5p and TLR4 were co-transfected into morphine-tolerant rats.Conclusion: MiR-140-5p inhibits morphine resistance in rats via targeted regulation of TLR4 expression. These provide a theoretical basis for the clinical management of morphine tolerance.