Possible pathophysiology of ketamine-related cystitis and associated treatment strategies

Int J Urol. 2015 Sep;22(9):816-25. doi: 10.1111/iju.12841. Epub 2015 Jun 18.


Ketamine-related cystitis is characterized by ketamine-induced urinary frequency and bladder pain. It has become a serious problem in recent years. The most typical grossly pathological bladder change with ketamine related cystitis is a contracted bladder and bladder wall thickening. Ulcerative cystitis with an easily bleeding mucosa is a common cystoscopic finding. Microscopically, the urothelium is denuded and is infiltrated by inflammatory cells, such as mast cells and eosinophils. The pathogenesis of ketamine-related cystitis is complicated and involves many different pathways. Past evidence suggests a direct toxic effect, bladder barrier dysfunction, neurogenic inflammation, immunoglobulin-E-mediated inflammation, overexpression of carcinogenic genes, abnormal apoptosis and nitric oxide synthase-mediated inflammation contribute to the pathogenesis of ketamine-related cystitis. The first step to managing ketamine-related cystitis is always asking patients to cease ketamine. Medical treatment might be helpful in patients with early ketamine-related cystitis and abstinence from ketamine. Several case studies showed that the intravesical installation of hyaluronic acid and intravesical injection of botulinum toxin type A were effective for symptom relief in selected patients. For patients with irreversible pathological change, such as contracted bladder, augmentation enterocystoplasty might be the only solution to increase bladder capacity and relieve intractable bladder pain.

Keywords: bladder pain; histology; inflammation; pharmacology; treatment.

Publication types

  • Review

MeSH terms

  • Acetylcholine Release Inhibitors / therapeutic use
  • Anesthetics, Dissociative / adverse effects*
  • Anesthetics, Dissociative / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Apoptosis
  • Botulinum Toxins, Type A / therapeutic use
  • Cholinergic Antagonists / therapeutic use
  • Cystitis / chemically induced*
  • Cystitis / genetics
  • Cystitis / pathology
  • Cystitis / physiopathology*
  • Cystitis / therapy
  • Drug Hypersensitivity / complications
  • Humans
  • Hyaluronic Acid / therapeutic use
  • Ketamine / adverse effects*
  • Ketamine / pharmacology
  • Neurogenic Inflammation / chemically induced
  • Nitric Oxide Synthase / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Steroids / therapeutic use
  • Urinary Bladder / drug effects*


  • Acetylcholine Release Inhibitors
  • Anesthetics, Dissociative
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cholinergic Antagonists
  • Steroids
  • Ketamine
  • Hyaluronic Acid
  • Nitric Oxide Synthase
  • Prostaglandin-Endoperoxide Synthases
  • Botulinum Toxins, Type A
  • incobotulinumtoxinA