2. Academic Validation
  3. Sodium leak channel contributes to neuronal sensitization in neuropathic pain

Sodium leak channel contributes to neuronal sensitization in neuropathic pain

  • Prog Neurobiol. 2021 Jul;202:102041. doi: 10.1016/j.pneurobio.2021.102041.
Donghang Zhang 1,  Wenling Zhao 1,  Jin Liu 1,  Mengchan Ou 1,  Peng Liang 2,  Jia Li 1,  Yali Chen 1,  Daqing Liao 3,  Siqi Bai 3,  Jiefei Shen 4,  Xiangdong Chen 5,  Han Huang 6,  Cheng Zhou 7
Affiliations

Affiliations

  • 1 Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China; Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
  • 2 Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
  • 3 Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
  • 4 Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases and Department of Prosthodontics, West China Stomatology Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
  • 5 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.
  • 6 Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China; Department of Anesthesiology & Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital of Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: [email protected].
  • 7 Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China; Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: [email protected].
PMID: 33766679 DOI: 10.1016/j.pneurobio.2021.102041
Abstract

Neuropathic pain affects up to 10 % of the total population and no specific target is ideal for therapeutic need. The sodium leak channel (NALCN), a non-selective cation channel, mediates the background Na+ leak conductance and controls neuronal excitability and rhythmic behaviors. Here, we show that increases of NALCN expression and function in dorsal root ganglion (DRG) and dorsal spinal cord contribute to chronic constriction injury (CCI)-induced neuropathic pain in rodents. NALCN current and neuronal excitability in acutely isolated DRG neurons and spinal cord slices of rats were increased after CCI which were decreased to normal levels by NALCN-siRNA. Accordingly, pain-related symptoms were significantly alleviated by NALCN-siRNA-mediated NALCN knockdown and completely prevented by NALCN-shRNA-mediated NALCN knockdown in rats or by conditional NALCN knockout in mice. Our results indicate that increases in NALCN expression and function contribute to CCI-induced neuronal sensitization; therefore, NALCN may be a novel molecular target for control of neuropathic pain.

Keywords

Dorsal root ganglion; Dorsal spinal cord; Neuronal sensitization; Neuropathic pain; Sodium leak channel.

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