title: Nerve hyperplasia: a unique feature of ketamine cystitis.
abstract: 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.
authors.affiliation: Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York, Heslington, York YO10 5DD, UK. simon.baker@york.ac.uk.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Baker
authors.forename: Jens
authors.initials: J
authors.lastname: Stahlschmidt
authors.forename: Jon
authors.initials: J
authors.lastname: Oxley
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hinley
authors.forename: Ian
authors.initials: I
authors.lastname: Eardley
authors.forename: Fiona
authors.initials: F
authors.lastname: Marsh
authors.forename: David
authors.initials: D
authors.lastname: Gillatt
authors.forename: Simon
authors.initials: S
authors.lastname: Fulford
authors.forename: Jennifer
authors.initials: J
authors.lastname: Southgate
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000009:adverse effects*; D003556:Cystitis / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D013287:Illicit Drugs; D007124:Immunoenzyme Techniques; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D000778:Anesthetics, Dissociative; D013287:Illicit Drugs; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D017475:Receptors, Nerve Growth Factor; D007649:Ketamine