Pre-treatment with morphine prevents lipopolysaccharide-induced acute respiratory distress syndrome in rats via activation of opioid receptors.

Exp Cell Res

Department of Anesthesiology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Research Center for Neuro-Oncology Interaction, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, PR China. Electronic address:

Published: September 2022

Purpose: Acute respiratory distress syndrome (ARDS), a severe medical condition, is among the major causes of death in critically ill patients. Morphine is used as a therapeutic agent against severe pain. The mechanisms of its reactions over ARDS are not fully understood. The aim of this study was to assess the mechanism of morphine in rats with ARDS.

Methods: Rats were injected with lipopolysaccharide to induce ARDS, and some rats were pre-treated with graded doses of morphine in the lateral ventricles to assess survival and non-infected mortality. Immunohistochemical and HE staining were performed to measure MPO and CD68 activity in the lungs and lung injury. ELISA was conducted to detect the inflammatory factor levels in the plasma and BALF. Co-labeling of μ-opioid receptor (MOR) and c-Fos was observed in the brain tissues. MOR-positive cells in brain tissues were evaluated using immunohistochemistry. The effect of MOR antagonists on ARDS was examined in rats by pre-injection of naloxone or methylnaltrexone. The expression of MyD88, TLR4, and NF-κB was lastly assessed.

Results: Dose-independent improvement was observed in respiratory capacity and lung injury in ARDS rats after morphine pre-injection, along with reduced inflammatory factors in the plasma and BALF. MOR-positive cells were elevated after morphine, which occurred within the ventral part of the gigantocellular reticular nucleus (GiV). Naloxone and methylnaltrexone blocked the effects of morphine via central and peripheral MOR. Morphine activated TLR pathway in a MyD88-dependent manner.

Conclusion: Morphine activates MOR within the GiV and the TLR pathway to attenuate ARDS in rats.

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http://dx.doi.org/10.1016/j.yexcr.2022.113224DOI Listing

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