Ketamine-induced bladder dysfunction

Introduction: Ketamine is a non-competitive antagonist that acts on N-methyl-D-aspartate (NMDA) receptors in the brain and has been used as an anaesthetic agent since the 1960s. It has more recently become popular as a party drug due to it’s hallucinogenic effects, however ketamine abusers can develop significant lower urinary tract symptoms with associated damage to the lining of the bladder that can be difficult to treat and can be referred to as ketamine-induced cystitis (KIC). Aims: i) To explore the neurogenic effects of ketamine, ii) To analyse histological features of ketamine cystitis specimens, iii) To contribute to existing preliminary evidence urothelial cells that express cKit are absent from ketamine-cystitis specimens. Methods: Immunolabelling of KIC specimens was performed to study specific biomarkers that included nerve growth factor receptor (NGFR), nerve filament protein (NFP), smooth muscle actin (SMA), vimentin, and cKit. Neuronal cell lines (B104 and LAN-5) were used to establish in vitro bioassays to study the effects of ketamine and NGF on neurite outgrowth. Normal human urothelial (NHU) cells were cultured in vitro and treated with ketamine to assess cKit protein expression using both RT-PCR and western blotting. Results: NGFR was seen to be upregulated in both urothelium and stroma of KIC specimens. SMA was expressed in urothelial cells however this was not seen in correlation with vimentin. cKit was absent in some KIC specimens, corroborated with decreased protein expression in vitro, however cKit transcript was upregulated in ketamine treated NHU cells. Neuronal cells treated with ketamine showed an increase in neurite outgrowth over the control (p<0.05). Conclusions: Upregulation of NGFR appears to be present in KIC specimens and could explain painful bladder symptoms. Whether this is caused directly or indirectly by ketamine has yet to be established. There is an absence of cKit expressing cells in the urothelium from some KIC specimens which requires further investigation.