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Immune mediators of chronic pelvic pain syndrome

Nature Reviews Urology volume 11, pages 259–269 (2014)Cite this article

Subjects

Key Points

  • Chronic pelvic pain syndrome (CPPS) is the most common classification of prostatitis and affects up to 16% of men at some point in their lives

  • CPPS is classified as an abacterial disease at time of diagnoses but acute bacterial infection might initiate inflammation and development of pain

  • Loss of regulation and suppression of CD4+ T-cell activity might result in constitutively active mast cells and loss of tolerance in CPPS

  • Mast-cell-released factors, such as tryptase and nerve growth factor, might mediate both inflammation and neural sensitization

  • CPPS has a complex aetiology, with evidence suggesting interplay between T cells, mast cells and neurons in the development of autoimmunity

Abstract

The cause of chronic pelvic pain syndrome (CPPS) has yet to be established. Since the late 1980s, cytokine, chemokine, and immunological classification studies using human samples have focused on identifying biomarkers for CPPS, but no diagnostically beneficial biomarkers have been identified, and these studies have done little to deepen our understanding of the mechanisms underlying chronic prostatic pain. Given the large number of men thought to be affected by this condition and the ineffective nature of current treatments, there is a pressing need to elucidate these mechanisms. Prostatitis types IIIa and IIIb are classified according to the presence of pain without concurrent presence of bacteria; however, it is becoming more evident that, although levels of bacteria are not directly associated with levels of pain, the presence of bacteria might act as the initiating factor that drives primary activation of mast-cell-mediated inflammation in the prostate. Mast cell activation is also known to suppress regulatory T cell (Treg) control of self-tolerance and also activate neural sensitization. This combination of established autoimmunity coupled with peripheral and central neural sensitization can result in the development of multiple symptoms, including pelvic pain and bladder irritation. Identifying these mechanisms as central mediators in CPPS offers new insight into the prospective treatment of the disease.

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Figure 1: Hypothetical model of chronic pelvic pain syndrome.
Figure 2: Hypothetical schematic representation of a modulated immune system in CPPS

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  1. Department of Urology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Tarry 16-760, Chicago, 60611, IL, USA

    Stephen F. Murphy, Anthony J. Schaeffer & Praveen Thumbikat

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S.F.M. and P.T. researched the literature, wrote, edited, and reviewed the article. A.J.S. made substantial contributions towards discussions of contents and reviewed the manuscript before submission.

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Correspondence to Praveen Thumbikat.

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Murphy, S., Schaeffer, A. & Thumbikat, P. Immune mediators of chronic pelvic pain syndrome. Nat Rev Urol 11, 259–269 (2014). https://doi.org/10.1038/nrurol.2014.63

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