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Summation model of pelvic pain in interstitial cystitis

Nature Clinical Practice Urology volume 5, pages 494–500 (2008)Cite this article

Abstract

Many patients with interstitial cystitis (IC) find that particular foods exacerbate disease symptoms. These patients may modify their diet to manage symptoms, but the mechanism by which dietary modification benefits patients with IC is unclear. We hypothesize that integration of neural signals from pelvic organs mediates the effects of diet on symptoms of IC. In animal models, pelvic inflammation is subject to crosstalk, so an inflammatory stimulus in one pelvic organ evokes a response in an independent organ. Recent data show that the colon can modulate bladder-associated pelvic pain in mice. As pelvic organs are innervated through shared circuitry, perceived pelvic pain might occur when spatial summation of individual pelvic inputs exceeds a threshold. Through this mechanism, a noxious dietary stimulus, which otherwise does not exceed the pain threshold in a normal individual, may substantially exacerbate pain in a patient with bladder symptoms. Repeated painful stimuli over time further contribute to symptoms by a process of temporal summation, resulting in enhanced responsiveness through central sensitization. Thus, pelvic organ crosstalk might modulate symptoms of pelvic pain by spatial and temporal summation, suggesting a mechanism for the benefits of dietary modification in patients with IC, as well as therapeutic opportunities.

Key Points

  • Animal studies have shown evidence of neurophysiological crosstalk between the bladder and bowel due to shared spinal and pelvic nerve circuitry; this communication may both positively and negatively modulate bladder-associated pelvic pain

  • Disparate regional stimuli can be integrated by spatial summation, and repetitive stimuli are integrated by temporal summation; therefore, we hypothesize that pain in interstitial cystitis (IC) is subject to summation by these mechanisms, resulting in exacerbation of bladder symptoms by dietary influences and time-dependent wind-up

  • Summation between a strong bladder pain signal and an otherwise subthreshold noxious dietary stimulus in the gastrointestinal tract may explain food sensitivities in patients with IC

  • The gastrointestinal tract and pelvic dermatome have the potential to be new sites for therapeutic intervention for pain symptoms in patients with IC

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Figure 1: The Pepperoni hypothesis: a summation model for pelvic pain.
Figure 2: Multimodal therapy for chronic pelvic pain.

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Acknowledgements

We thank Dr Anthony Schaeffer and Dr Praveen Thumbikat for many helpful discussions, and Dr Thumbikat for coining the term “Pepperoni hypothesis”. This work was supported by NIDDK awards R01DK066112 (DJ Klumpp) and T32DK062716-05 (CN Rudick).

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Authors and Affiliations

  1. DJ Klumpp is Assistant Professor in the Departments of Urology and Microbiology–Immunology and CN Rudick is NIDDK Postdoctoral Fellow in the Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,

    David J Klumpp & Charles N Rudick

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  1. David J Klumpp
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  2. Charles N Rudick
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Correspondence to David J Klumpp.

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Klumpp, D., Rudick, C. Summation model of pelvic pain in interstitial cystitis. Nat Rev Urol 5, 494–500 (2008). https://doi.org/10.1038/ncpuro1203

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