{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T15:38:59Z","timestamp":1771515539585,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,12,24]],"date-time":"2013-12-24T00:00:00Z","timestamp":1387843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Funda\u00ef\u00bf\u00bd\u00ef\u00bf\u00bdo para a Ci\u00ef\u00bf\u00bdncia e Tecnologia","award":["SFRH\/BPD\/68716\/2010"],"award-info":[{"award-number":["SFRH\/BPD\/68716\/2010"]}]},{"name":"InComb FP7 HEALTH","award":["project no 223234"],"award-info":[{"award-number":["project no 223234"]}]},{"name":"NIH","award":["R37 DK54824"],"award-info":[{"award-number":["R37 DK54824"]}]},{"name":"NIH","award":["R01 DK57284"],"award-info":[{"award-number":["R01 DK57284"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>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\u2010like bladder modifications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical study\u2014In BPS\/IC patients and aged and body mass index matched volunteers TILT test was undertaken and catecholamines were measured in plasma and 24\u2009hr urine samples. Experimental study\u2014Phenylephrine 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\u20101\u2010adrenoreceptor and TRPV1 in suburothelial nerves. Mast cell number was determined in the sub\u2010urothelium. In rats with lipopolysaccharide\u2010induced cystitis, urinary catecholamines, and Vesicular Monoamine Transporter 2 (VMAT2) expression in bladder nerves were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The TILT test showed an increase of sympathetic activity. Noradrenaline levels in blood at resting conditions and in 24\u2010hr 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\u2010expressed alpha1 and TRPV1. Mastocytosis was present in the suburothelium. Cystitis increased sympathetic nerve density and urinary noradrenaline levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Excessive adrenergic stimulation of the bladder may contribute to the pathophysiological mechanisms of BPS\/IC. <jats:italic>Neurourol. Urodynam. 34:489\u2013496, 2015<\/jats:italic>. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.22542","type":"journal-article","created":{"date-parts":[[2013,12,24]],"date-time":"2013-12-24T11:10:51Z","timestamp":1387883451000},"page":"489-496","source":"Crossref","is-referenced-by-count":33,"title":["Can the adrenergic system be implicated in the pathophysiology of bladder pain syndrome\/interstitial cystitis? A clinical and experimental study"],"prefix":"10.1002","volume":"34","author":[{"given":"Ana","family":"Charrua","sequence":"first","affiliation":[{"name":"Department of Experimental Biology Faculty of Medicine University of Porto Porto Portugal"},{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular University of Porto Porto Portugal"},{"name":"Department of Renal Urologic and Infectious Disease Faculty of Medicine University of Porto Porto Portugal"},{"name":"Department of Urology S. Jo\u00e3o Hospital Porto Portugal"}]},{"given":"Rui","family":"Pinto","sequence":"additional","affiliation":[{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular University of Porto Porto Portugal"},{"name":"Department of Renal Urologic and Infectious Disease Faculty of Medicine University of Porto Porto Portugal"},{"name":"Department of Urology S. Jo\u00e3o Hospital Porto Portugal"}]},{"given":"Anna","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics McGill University Montreal Quebec Canada"}]},{"given":"Andr\u00e9","family":"Canelas","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology Faculty of Medicine University of Porto Porto Portugal"}]},{"given":"Alfredo","family":"Ribeiro\u2010da\u2010Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics McGill University Montreal Quebec Canada"}]},{"given":"C\u00e9lia D.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology Faculty of Medicine University of Porto Porto Portugal"},{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular University of Porto Porto Portugal"}]},{"given":"Lori Ann","family":"Birder","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pharmacology\u2010Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}]},{"given":"Francisco","family":"Cruz","sequence":"additional","affiliation":[{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular University of Porto Porto Portugal"},{"name":"Department of Renal Urologic and Infectious Disease Faculty of Medicine University of Porto Porto Portugal"},{"name":"Department of Urology S. 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