PBS/IC is often regarded as a neurogenic cystitis due to symptoms that include pelvic and/or perineal pain, urinary frequency, urgency and nocturia. A model of pathogenesis involves a positive feedback loop, whereby substance P containing nerves stimulate mast cells, in turn releasing inflammatory mediators that induce urothelial inflammation. Histamine release by mast cells feeds back onto nerves to induce the further release of substance P and mast cell activation.

Chen and colleagues from Northwestern University developed a murine model of neurogenic cystitis using Bartha's strain of pseudorabies virus (PRV) based on a similar model in the rat. PRV induced neurogenic cystitis with markers of acute and chronic inflammation.

The focal nature was reminiscent of PBS/IC. Bladder mast cells trafficked from the distal detrusor into the lamina propria and activated mast cells were increased in the lamina propria. In tumor necrosis factor receptor-deficient mice infected with PRV, mast cell trafficking and activation were not observed, indicating a central role for tumor necrosis factor in the events of neurogenic cystitis.

The authors speculate that blocking mast cell migration to the lamina propria and also blocking mast cell activation would minimize the mast cell activation of pain causing C-fibers. Therefore, anti tumor necrosis factor therapy might mitigate C-fiber signaling in neurogenic cystitis by maintaining mast cell distance from C-fibers and stabilizing mast cells in a resting state.

This line of reasoning seems worthwhile pursuing.

J. Urol, 175:754-759 (February), 2006.

: Philip M Hanno, MD, MPH

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