Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis

Area of Science:

• Urology
• Pathology
• Pharmacology

Background:

• Ketamine cystitis (KC) is a chronic bladder condition characterized by inflammation, pain, urinary urgency, and frequency.
• The pathogenesis of KC is multifactorial, involving urothelium disruption, lamina propria fibrosis and inflammation, microvascular injury, neuropathological alterations, and bladder smooth muscle (BSM) abnormalities.

Purpose of the Study:

• To elucidate the signaling pathways through which ketamine induces tissue injuries in the bladder.
• To clarify the role of specific signaling pathways in the pathophysiology of ketamine-induced cystitis.

Main Methods:

• Review of recent studies on ketamine's effects on bladder tissue.
• Analysis of signaling pathways involved in urothelium disruption, lamina propria changes, microvascular injury, BSM abnormalities, and neuropathological alterations.

Main Results:

• Ketamine disrupts urothelium via antiproliferative factor, ATP, and oxidative stress.
• Lamina propria fibrosis/inflammation involve COX-2, NOS, IgE, and TGF-β1.
• Microvascular injury is mediated by NMDAR, TNF-α, and VEGF.
• BSM abnormalities are linked to suppressed AKT, ERK, Cav1.2, muscarinic receptor signaling, and elevated purinergic signaling.
• Neuropathological changes involve NMDAR, BDNF, and inflammatory mediators.

Conclusions:

• Ketamine induces diverse bladder tissue injuries through specific signaling pathways.
• Understanding these pathways is crucial for developing effective treatments for ketamine cystitis.