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.
Naunyn-Schmiedeberg's archives of pharmacology. 2017 May 31 [Epub ahead of print]
Rita Matos, Paula Serrão, Larissa Rodriguez, Lori Ann Birder, Francisco Cruz, Ana Charrua
Departamento de Biomedicina - Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal., Departamento de Biomedicina - Unidade de Farmacêutica e Terapêutica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal., Departments of Urology and Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA., Departments of Medicine and Pharmacology-Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal., Departamento de Biomedicina - Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal. .