Clinical Trial: Changes in Inflammatory and Contractile Protein Expression in Patients With Painful Bladder Syndrome/IC.

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Mediators of Neurogenic Inflammation in the Urinary Tract as Key Factors in the Painful Bladder Syndrome / Interstitial Cystitis and Bladder Dysfunction

Brief Summary: Interstitial cystitis (IC)/chronic pelvic pain syndrome (CPPS) is a clinical syndrome of pelvic pain and/or urinary urgency/frequency in absence of a specific cause such as bacterial infection or damage to the bladder. The pathogenetic mechanisms of IC/CPPS are as yet undefined and it is largely this lack of knowledge, which precludes a systematic therapeutic approach. Experimental evidence, including results from the animal models of cystitis and the knock-out mice, indicate a participation of tachykinin receptors, especially the NK1R, in neurogenic inflammation, which is considered an important element of the IC complex. However, there is very scant information about the molecular mechanisms of IC in humans, or of the types of receptors, which participate in neurogenic inflammation. Based on our molecular biological know-how and the clinical expertise, we propose to investigate the role of the tachykinin and bradykinin receptors and their signalling partners in CPPS and bladder dysfunction in humans.

Detailed Summary:

Although IC has been recognised for more than a century, its pathophysiology remains a mystery, and as a consequence the treatment of IC is largely empirical. A multitude of mechanisms of the disease have been postulated ranging from neuroinflammatory to autoimmune or possibly infectious or toxic agents. Newer studies have hinted towards a genetic basis of the disease, but in most hypotheses an inflammatory component of some kind is involved and many findings support this theory. An often-cited hypothesis is the leaky epithelium. The healthy bladder is coated with a thin mucinous substance bladder surface mucin, which is composed of numerous sulfonated glycosaminoglycans and glycoproteins. In IC patients, in contrast to controls, as well as in some animal models of IC, qualitative changes to this surface layer have been observed (Lilly et al, 1990., Moskowitz et al, 1994). An initiating event (toxin) may lead to functional changes and increased permeability. This in turn leads to nerve sensitisation and possibly up-regulation. There is increasing evidence that the progression of IC is accompanied by a significant up-regulation of sensory nerves in the bladder (Letourneau, 1996). Nerve growth factor (NGF), a neurotropin that sensitises nociceptor fibres, was reported to be increased in bladders of IC patients (Lowe, 1997), and application of NGF in Wistar rats acutely induced bladder hyperactivity (Chuang, 2001). Sensory nerves in neurogenic inflammation secrete inflammatory mediators such as Substance P (SP), a nociceptive neurotransmitter in the central and peripheral nervous system. Increased amounts of the released Substance P have been found in the urine of IC patients (Hohenfellner, et al,1992, Pang et al., 1995, Pang et al., 1996), the concentration of Substance P reflecting the patients' degree of pain (Chen et al., 1999). Substance P and related tachykinins (TKs) mediate a variety of physiological processes in th
Sponsor: University Hospital Inselspital, Berne

Current Primary Outcome: Receptor expression in disease states versus control [ Time Frame: at time of biospy ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University Hospital Inselspital, Berne

Dates:
Date Received: October 17, 2008
Date Started: October 2006
Date Completion:
Last Updated: April 25, 2010
Last Verified: April 2010