Nerve hyperplasia: a unique feature of ketamine cystitis

Simon C. Baker*, Jens Stahlschmidt, Jon Oxley, Jennifer Hinley, Ian Eardley, Fiona Marsh, David Gillatt, Simon Fulford, Jennifer Southgate

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


Background: There is an emerging association between ketamine abuse and the development of urological symptoms including dysuria, frequency and urgency, which have a neurological component. In addition, extreme cases are associated with severe unresolving bladder pain in conjunction with a thickened, contracted bladder and an ulcerated/absent urothelium. Here we report on unusual neuropathological features seen by immunohistology in ketamine cystitis. Results: In all cases, the lamina propria was replete with fine neurofilament protein (NFP+) nerve fibres and in most patients (20/21), there was prominent peripheral nerve fascicle hyperplasia that showed particular resemblance to Morton's neuroma. The nerve fascicles, which were positive for NFP, S100 and the p75 low-affinity nerve growth factor receptor (NGFR), were generally associated with a well-developed and in places, prominent, epithelial membrane antigen+/NGFR+ perineurium. This peripheral nerve fascicle hyperplasia is likely to account for the extreme pain experienced by ketamine cystitis patients. Urothelial damage was a notable feature of all ketamine cystitis specimens and where urothelium remained, increased NGFR expression was observed, with expansion from a basal-restricted normal pattern of expression into the suprabasal urothelium. Conclusions: The histological findings were distinguishing features of ketamine cystitis and were not present in other painful bladder conditions. Ketamine cystitis afflicts predominantly young patients, with unknown long-term consequences, and requires a strategy to control severe bladder pain in order to remove a dependency on the causative agent. Our study indicates that the development of pain in ketamine cystitis is mediated through a specific neurogenic mechanism that may also implicate the urothelium.

Original languageEnglish
Article number64
Pages (from-to)1-7
Number of pages7
JournalActa Neuropathologica Communications
Publication statusPublished - 8 Oct 2013
Externally publishedYes


  • Bladder pain
  • Cystitis
  • Ketamine
  • Nerve
  • Neurofilament protein
  • P75 nerve growth factor receptor
  • Urothelium


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