CE/CME

Interstitial Cystitis: A Painful Syndrome

Clinician Reviews. 2013 July;23(7):30-37

References

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2. Hanno PM, Burks DA, Clemens JQ, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: American Urological Association (AUA) Guideline (2011). www.auanet.org/education/guidelines/ic-bladder-pain-syndrome.cfm. Accessed June 5, 2013.

3. Evans RJ; University of Tennessee Advanced Studies in Pharmacy. Pathophysiology and clinical presentation of interstitial cystitis (2005). www.utasip.com/files/articlefiles/pdf/XASIP_Issue_Mar_p8_14.pdf. Accessed June 5, 2013.

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6. van de Merwe JP, Nordling J, Bouchelouche P, et al. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol. 2008;53:60-67.

7. Bogart LM, Berry SH, Clemens JQ. Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: a systematic review.  J Urol. 2007;177:450-456.

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THE PROPOSED PATHOPHYSIOLOGY
IC/BPS is thought to begin with an initial insult to the bladder that leads to dysfunction of the epithelial layer. This insult may be the result of a neurogenic inflammation, autoimmunity, subclinical or chronic infection, or bladder urothelial defects.¹ Dysfunction in the epithelial layer includes altered bladder epithelial expression of human leukocyte antigen I and II; decreased expression of uroplakin (an antitoxic protein in the bladder), and a defective glycosaminoglycan mucus layer.⁴ This damage to the epithelial layer alters the permeability of the bladder, allowing potassium ions to enter the urothelium and depolarize motor and sensory nerves. This potassium leak then activates the mast cells, causing mastocytosis and the release of histamine.¹¹ These processes disrupt the homeostasis of the urinary tract and allow the development of inflammation—a main cause of the pelvic pain associated with IC/BPS^4,12,13 (see Figure 1¹⁴).

Other factors that exacerbate the primary inflammation in the bladder are C-fibers and nerve growth factor (NGF). C-fibers are afferent fibers found in the peripheral nerves of the somatic sensory system that convey input signals from the periphery to the central nervous system.³ In patients with IC/BPS, initial inflammation activates C-fibers, which produce substance P, nociceptor, and other inflammatory mediators. These mediators exacerbate existing inflammation and further facilitate mast cell activation.³

NGF is a protein that is critical for the maintenance of sympathetic and sensory neurons; it is important not only in the urinary tract but in all organ systems. Increased levels of NGF, a prevalent finding in patients with IC/BPS, is an indicator of inflammation in the body. The precise mechanism that causes elevated NGF in patients with IC/BPS is not well understood, but its presence supports the theory that inflammation is a cause of pelvic pain in IC/BPS.¹²

The urinary urgency and frequency experienced by patients with IC/BPS is in part due to the role nitric oxide (NO) plays in bladder activity. Patients with IC have decreased levels of urinary NO (a reduction thought to be the result of a decrease in L-arginine) and urinary NO synthase.^12,15,16 Ordinarily, NO synthase converts L-arginine to NO, which helps to control relaxation of the bladder smooth muscle, allowing more urine to be stored. In patients with IC/BPS, NO insufficiency leads to bladder overactivity.¹⁵

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