Qingmei Li,1,* Shuming Liu,2,* Bangyong Qin,3 Xingfeng Liu4,5 

1Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China; 2Department of Anesthesiology, The Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China; 3Department of Pain Medicine, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China; 4Guizhou Key Laboratory of Brain Science, Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 5Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, 563000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Bangyong Qin; Xingfeng Liu, Email qbyzy@163.com; xingfengliu@zmu.edu.cn

Abstract: This review systematically summarizes the research progress of ketamine and its interaction with specific brain regions in the context of neuropathic pain comorbid with depression. As a non-competitive inhibitor of N-methyl-D-aspartate (NMDA) receptors, Ketamine exerts complex mechanisms and controversial topic. The structure and function of NMDA receptors, as well as the binding sites of ketamine, are summarized, and the hypothesis of disinhibition and neuroplasticity of ketamine’s antidepressant effect is elaborated. The mechanism of key brain regions, such as hippocampus and anterior cingulate cortex, is discussed in detail, and the antidepressant effect of ketamine is explored from the perspective of transcriptomics. Finally, this review integrates bioinformatics, molecular biology and other interdisciplinary approaches to elucidate the therapeutic effects and potential mechanisms of ketamine in treating neuropathic pain and depression comorbidity, providing a comprehensive theoretical basis, new directions for subsequent research and novel insights for the clinical application of ketamine.

Keywords: ketamine, neuropathic pain, depression, specific brain regions