NADPH-Oxidase 2 Promotes Autophagy in Spinal Neurons During the Development of Morphine Tolerance

Neurochemical Research - Tập 46 - Trang 2089-2096 - 2021
Xuyang Xiao1, Huilian Bu2, Zhisong Li1, Zheng Li3, Qian Bai1, Zhitao Wang1, Lin Yan3, Daiqiang Liu3, Xiaoling Peng3, Xiaoqian Jia3, Feng Gao3
1Department of Anesthesiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
2Department of Pain Management, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Tóm tắt

Repeated morphine administration results in analgesic tolerance. However, the underlying mechanism of morphine analgesic tolerance remains unclear. NADPH-oxidase 2 (NOX2) is the first discovered NADPH oxidase, which mainly functions to produce reactive oxygen species. Its specific role in morphine tolerance has not been fully investigated. In this work, we found that chronic morphine administration significantly increased the expression of NOX2 in spinal cord. Pretreatment of NOX2 inhibitor blocked the upregulation of NOX2 and autophagy markers, including LC3B and P62, and consequently the development of morphine tolerance. NOX2 and LC3B were both colocalized with NeuN in spinal dorsal horn in morphine-tolerant rats. Our results suggest that the increased autophagy activity in spinal neurons promoted by NOX2 activation contributes to the development of morphine tolerance. NOX2 may be considered as a new therapeutic target for morphine tolerance.

Tài liệu tham khảo

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