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Acta Neuropathol Commun. 2013 Oct 8;1:64. doi: 10.1186/2051-5960-1-64.

Nerve hyperplasia: a unique feature of ketamine cystitis.

Author information

1
Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York, Heslington, York YO10 5DD, UK. simon.baker@york.ac.uk.

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.

PMID:
24252413
PMCID:
PMC3893507
DOI:
10.1186/2051-5960-1-64
[Indexed for MEDLINE]
Free PMC Article

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