Increased number of substance P positive nerve fibres in interstitial cystitis

TLDR

Substance P, a pain‑associated neuropeptide that stimulates mast cell secretion and is potentiated by estrogen, may drive the neuro‑inflammatory and painful features of interstitial cystitis. The study sought to determine the presence of substance P in rat and human bladders and its relationship to mast cells in interstitial cystitis. Bladder biopsies from eight IC patients, five controls, and 12 rats were examined by immunohistochemistry and image analysis to quantify substance P‑positive nerve fibre density and its proximity to mast cells. Substance P‑positive nerve fibres were detected in both species, but were markedly increased in the submucosa of IC patients and frequently adjacent to mast cells.

Abstract

Objective To explore the presence of the neuropeptide substance P (SP) in the bladders of rats and humans and to investigate its relationship to mast cells (MCs) in interstitial cystitis (IC), a bladder disorder which occurs mostly in women and is characterized by frequency of voiding, nocturia and debilitating supra‐pubic pain. Patients, materials and methods Bladder biopsies from eight women with untreated IC (mean age 36 years, range 29‐58) and five control patients with no IC were analysed and compared with each other and with bladder tissue from 12 rats. Immuno‐histochemistry and image analysis were used to examine the density of SP‐positive nerve fibres and their relationship with MCs. Results SP‐containing nerve fibres were present in the bladder of both rats and humans. They were increased only in the submucosa, but not in the detrusor, of IC patients and were frequently seen in juxtaposition to MCs. Conclusion SP, a neuropeptide secreted from sensory nerve endings, has been implicated in the pathophysio‐logy of pain and has been shown to trigger MC secretion. Moreover, MC secretion by SP is augmented by oestradiol and bladder MCs have been shown to express high affinity oestrogen receptors. A functional relationship between SP and MCs may explain the pathophysiology of the neuro‐inflammatory and painful nature of IC.