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Can the adrenergic system be implicated in the pathophysiology of bladder pain syndrome/interstitial cystitis? A clinical and experimental study

Authors

  • Ana Charrua,

    1. Department of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal
    2. IBMC – Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
    3. Department of Renal, Urologic and Infectious Disease, Faculty of Medicine, University of Porto, Porto, Portugal
    4. Department of Urology, S. João Hospital, Porto, Portugal
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  • Rui Pinto,

    1. IBMC – Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
    2. Department of Renal, Urologic and Infectious Disease, Faculty of Medicine, University of Porto, Porto, Portugal
    3. Department of Urology, S. João Hospital, Porto, Portugal
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  • Anna Taylor,

    1. Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    Current affiliation:
    1. Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA
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  • André Canelas,

    1. Department of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal
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  • Alfredo Ribeiro-da-Silva,

    1. Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
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  • Célia D. Cruz,

    1. Department of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal
    2. IBMC – Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
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  • Lori Ann Birder,

    1. Departments of Medicine and Pharmacology-Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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  • Francisco Cruz

    Corresponding author
    1. IBMC – Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
    2. Department of Renal, Urologic and Infectious Disease, Faculty of Medicine, University of Porto, Porto, Portugal
    3. Department of Urology, S. João Hospital, Porto, Portugal
    • Correspondence to: Francisco Cruz, M.D., Ph.D., IBMC – Instituto de Biologia Molecular e Celular, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal. E-mail: cruzfjmr@med.up.pt

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  • Karl-Erik Andersson led the peer-review process as the Associate Editor responsible for the paper.
  • Ana Charrua and Rui Pinto contributed equally to this work.
  • Conflict of interest: None.

Abstract

Aims

To evaluate sympathetic system activity in bladder pain syndrome/interstitial cystitis (BPS/IC) patients and to investigate if chronic adrenergic stimulation in intact rats induces BPS/IC-like bladder modifications.

Methods

Clinical study—In BPS/IC patients and aged and body mass index matched volunteers TILT test was undertaken and catecholamines were measured in plasma and 24 hr urine samples. Experimental study—Phenylephrine was injected subcutaneously (14 days) to female Wistar rats. Pain behavior, spinal Fos expression, urinary spotting, number of fecal pellets expelled, frequency of reflex bladder contractions, and urothelial height were analyzed. Urothelium permeability was investigated by trypan blue staining. Immunoreactivity against caspase 3 and bax were studied in the urothelium and against alpha-1-adrenoreceptor and TRPV1 in suburothelial nerves. Mast cell number was determined in the sub-urothelium. In rats with lipopolysaccharide-induced cystitis, urinary catecholamines, and Vesicular Monoamine Transporter 2 (VMAT2) expression in bladder nerves were analyzed.

Results

The TILT test showed an increase of sympathetic activity. Noradrenaline levels in blood at resting conditions and in 24-hr urine samples were higher in BPS/IC patients. Phenylephrine administration increased visceral pain, spinal Fos expression, bladder reflex activity, urinary spotting and the number of expelled fecal pellets. The mucosa showed urothelial thinning and increased immunoreactivity for caspase 3 and bax. Trypan blue staining was only observed in phenylephrine treated animals. Suburothelial nerves co-expressed alpha1 and TRPV1. Mastocytosis was present in the suburothelium. Cystitis increased sympathetic nerve density and urinary noradrenaline levels.

Conclusions

Excessive adrenergic stimulation of the bladder may contribute to the pathophysiological mechanisms of BPS/IC. Neurourol. Urodynam. 34:489–496, 2015. © 2013 Wiley Periodicals, Inc.

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