Increased expression of substance P receptor-encoding mRNA in bladder biopsies from patients with interstitial cystitis.

Abstract

To determine whether substance P (SP, also known as neurokinin 1, NK1) receptors are differentially expressed in bladder biopsies from patients with interstitial cystitis (IC) compared with matched controls. Cold-cup biopsies were taken during routine diagnostic cystoscopy. NK1-receptor expression was assessed using a quantitative analysis of NK1-receptor-encoding mRNA in bladder biopsies from patients and controls using in situ hybridization histochemistry (ISHH) combined with autoradiographic image analysis. Autoradiographic signal indicating the presence of NK1-encoding mRNA was localized to detrusor muscle, urothelium and vascular structures. In the bladder vasculature, the signal was predominantly associated with endothelial cells. NK1 receptor-encoding mRNA within the vascular endothelium was increased in the biopsies obtained from patients with IC. Increased levels of NK1 receptor-encoding mRNA within the bladder vascular endothelium suggests the up-regulation of NK1 receptor as a putative factor in the pathogenesis of pain related to IC. Increased responsiveness to SP released from the perivascular sensory terminals may result in a local cascade of neurogenic inflammatory responses which trigger the pathophysiological changes, including pain, characteristic of IC.