Ana Charrua1,2,3,4, Rui Pinto2,3,4, Anna Taylor5, André Canelas1, Alfredo Ribeiro-da-Silva5, Célia D Cruz1,2, Lori Ann Birder6, Francisco Cruz2,3,4. 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. 5. Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada. 6. Departments of Medicine and Pharmacology-Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
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.
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.
Authors: Y Igawa; Y Yamazaki; H Takeda; K Hayakawa; M Akahane; Y Ajisawa; T Yoneyama; O Nishizawa; K E Andersson Journal: Br J Pharmacol Date: 1999-02 Impact factor: 8.739
Authors: Dean A Tripp; J Curtis Nickel; Jennifer Wong; Michel Pontari; Robert Moldwin; Robert Mayer; Lesley K Carr; Ragi Doggweiler; Claire C Yang; Nagendra Mishra; Jorgen Nordling Journal: Eur Urol Date: 2012-05-18 Impact factor: 20.096
Authors: Rita Matos; Paula Serrão; Larissa Rodriguez; Lori Ann Birder; Francisco Cruz; Ana Charrua Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2017-05-31 Impact factor: 3.000
Authors: Ana Paula Cardoso-de-Mello-E-Mello-Ribeiro; Cleofás Rodríguez-Blanco; Inmaculada Riquelme-Agulló; Alberto Marcos Heredia-Rizo; François Ricard; Ángel Oliva-Pascual-Vaca Journal: Evid Based Complement Alternat Med Date: 2015-06-14 Impact factor: 2.629
Authors: Folabomi A Oladosu; Kevin M Hellman; Paula J Ham; Laura E Kochlefl; Avisek Datta; Ellen F Garrison; Nicole D Steiner; Genevieve E Roth; Frank F Tu Journal: Sci Rep Date: 2019-02-18 Impact factor: 4.379
Authors: Sara Dinis; Joana Tavares de Oliveira; Rui Pinto; Francisco Cruz; Ca Tony Buffington; Paulo Dinis Journal: Int J Womens Health Date: 2015-07-23