Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 390, Issue 8, pp 839–844 | Cite as

The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation

  • Rita Matos
  • Paula Serrão
  • Larissa Rodriguez
  • Lori Ann Birder
  • Francisco Cruz
  • Ana Charrua
Original Article


Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.


Chronic stress Visceral pain Alpha 1A adrenoceptor Silodosin 



Ana Charrua is supported by Fundação para a Ciência e Tecnologia (FCT) fellowship SFRH/BPD/68716/2010.

This work was supported by the PFD Research Foundation and ICA IC/PBS Research Grant.

Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interests.

Lori Ann Birder has a research grant from Astellas Pharma.

Francisco Cruz is consultant/investigator/speaker for Astellas, Ipsen, Recordati and Allergan.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Departamento de Biomedicina - Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do PortoPortoPortugal
  2. 2.i3S - Instituto de Investigação e Inovação em SaúdeUniversidade do PortoPortoPortugal
  3. 3.IBMC – Instituto de Biologia Molecular e CelularUniversidade do PortoPortoPortugal
  4. 4.Departamento de Biomedicina - Unidade de Farmacêutica e Terapêutica, Faculdade de Medicina da Universidade do PortoPortoPortugal
  5. 5.MedInUP – Center for Drug Discovery and Innovative MedicinesUniversity PortoPortoPortugal
  6. 6.Departments of Urology and Obstetrics and GynecologyUniversity of Southern CaliforniaLos AngelesUSA
  7. 7.Departments of Medicine and Pharmacology-Chemical BiologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  8. 8.Department of UrologyHospital S. JoãoPortoPortugal
  9. 9.Departamento de BiomedicinaCentro de Investigação Médica, Faculdade de Medicina do PortoPortoPortugal

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