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

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

  • Neurochem Res. 2021 Aug;46(8):2089-2096. doi: 10.1007/s11064-021-03347-5.
Xuyang Xiao  # 1 Huilian Bu  # 2 Zhisong Li 1 Zheng Li 3 Qian Bai 1 Zhitao Wang 1 Lin Yan 3 Daiqiang Liu 3 Xiaoling Peng 3 Xiaoqian Jia 3 Feng Gao 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 2 Department of Pain Management, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 3 Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • # Contributed equally.
Abstract

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.

Keywords

Autophagy; Morphine tolerance; NADPH oxidase; Reactive oxygen species.

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