The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation
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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.
KeywordsChronic 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.
- Choo MS, Song M, Kim JH, Lee KS, Kim JC, Kim SW, Yang SK, Lee JG, Lee JZ, Kim DK, Park WH, Kim KD, Na YG, Kwon DD, Paick JS (2014) Safety and efficacy of 8-mg once-daily vs 4-mg twice-daily silodosin in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (SILVER study): a 12-week, double-blind, randomized, parallel, multicenter study. Urology 83:875–881CrossRefPubMedGoogle Scholar
- Cruz CD, Avelino A (2012) Animal models of cystitis. In: Szallasi A, Biró T (eds) TRP channels in drug discovery. Humana Press, New York CityGoogle Scholar
- Eisenhardt A, Schneider T, Cruz F, Oelke M (2014) Consistent and significant improvement of nighttime voiding frequency (nocturia) with silodosin in men with LUTS suggestive of BPH: pooled analysis of three randomized, placebo-controlled, double-blind phase III studies. World J Urol 32:1119–1125CrossRefPubMedGoogle Scholar
- Matos R, Cordeiro JM, Coelho A, Ferreira S, Silva C, Igawa Y, Cruz F, Charrua A (2016) Bladder pain induced by prolonged peripheral alpha 1A adrenoceptor stimulation involves the enhancement of transient receptor potential vanilloid 1 activity and an increase of urothelial adenosine triphosphate release. Acta Physiol (Oxf) 218:265–275CrossRefGoogle Scholar
- Shah H (2011) How to calculate sample size in animal studies? Natl J Physiol Pharm Pharmacol 1:5Google Scholar
- Smith AL, Leung J, Kun S, Zhang R, Karagiannides I, Raz S, Lee U, Glovatscka V, Pothoulakis C, Bradesi S, Mayer EA, Rodriguez LV (2011) The effects of acute and chronic psychological stress on bladder function in a rodent model. Urology 78(967):e1–e7Google Scholar