Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis.

Xiang Xie, Jiayu Liang, Run Huang, Chuang Luo, Jiali Yang, Hongming Xing, Le Zhou, Han Qiao, Erti Ergu, Huan Chen

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2021 Jul

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Ketamine cystitis (KC) is a chronic bladder inflammation leading to urinary urgency, frequency, and pain. The pathogenesis of KC is complicated and involves multiple tissue injuries in the bladder. Recent studies indicated that urothelium disruption, lamina propria fibrosis and inflammation, microvascular injury, neuropathological alterations, and bladder smooth muscle (BSM) abnormalities all contribute to the pathogenesis of KC. Ketamine has been shown to induce these tissue injuries by regulating different signaling pathways. Ketamine can stimulate antiproliferative factor, adenosine triphosphate, and oxidative stress to disrupt urothelium. Lamina propria fibrosis and inflammation are associated with the activation of cyclooxygenase-2, nitric oxide synthase, immunoglobulin E, and transforming growth factor β1. Ketamine contributes to microvascular injury via the N-methyl-D aspartic receptor (NMDAR), and multiple inflammatory and angiogenic factors such as tumor necrosis factor α and vascular endothelial growth factor. For BSM abnormalities, ketamine can depress the protein kinase B, extracellular signal-regulated kinase, Cav1.2, and muscarinic receptor signaling. Elevated purinergic signaling also plays a role in BSM abnormalities. In addition, ketamine affects neuropathological alterations in the bladder by regulating NMDAR- and brain-derived neurotrophic factor-dependent signaling. Inflammatory cells also contribute to neuropathological changes via the secretion of chemical mediators. Clarifying the role and function of these signaling underlying tissue injuries in the bladder with KC can contribute to a better understanding of the pathophysiology of this disease and to the design of effective treatments for KC. © 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

Citation

Xiang Xie, Jiayu Liang, Run Huang, Chuang Luo, Jiali Yang, Hongming Xing, Le Zhou, Han Qiao, Erti Ergu, Huan Chen. Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2021 Jul;35(7):e21703