Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/101026
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dc.creatorFrias, B.
dc.creatorCharrua, Ana
dc.creatorAvelino, A.
dc.creatorMichel, M.C.
dc.creatorCruz, F.
dc.creatorCruz, C.D.
dc.date.accessioned2019-02-05T02:15:03Z-
dc.date.available2019-02-05T02:15:03Z-
dc.date.issued2012
dc.identifier.othersigarra:48034
dc.identifier.urihttps://repositorio-aberto.up.pt/handle/10216/101026-
dc.description.abstractOBJECTIVES To explore the role of transient receptor potential vanilloid 1 (TRPV1) in the excitatory effects of chronic administration of nerve growth factor (NGF) on bladder-generated sensory input and reflex activity. To explore new therapeutic targets for bladder dysfunction. MATERIALS AND METHODS Wild-type (WT) and TRPV1 knockout (KO) mice received daily intraperitoneal injections of NGF (1 mu g/10 g) or saline for a period of 4 days, during which time thermal sensitivity was evaluated daily. On the 5th day, mice were anaesthetized and cystometries were performed. The frequency, amplitude and area under the curve (AUC) of bladder reflex contractions were determined. c-Fos expression was evaluated on L6 spinal cord sections of WT and TRPV1 KO mice treated with saline or chronic NGF by immunohistochemistry. TrkA receptor staining intensity was determined in L6 spinal cord sections and respective dorsal root ganglia of WT and TRPV1 KO mice. RESULTS Repeated administration of NGF induced thermal hypersensitivity in WT but not in TRPV1 KO mice. The frequency of bladder contractions of saline-treated WT and TRPV1 KO mice was similar, the values respectively being 0.45 +/- 0.12/min and 0.46 +/- 0.16/min. Treatment with NGF enhanced bladder reflex activity in WT mice to 1.23 +/- 0.41/min (P < 0.05). In NGF-treated KO mice, the frequency of bladder contractions was 0.60 +/- 0.05/min. Irrespective of treatment, no differences were observed in the amplitude of bladder contractions of WT and TRPV1 KO mice. The AUC was significantly increased in NGF-treated WT-mice, when compared with saline-treated WT-mice. No changes were found in AUC of saline-treated and NGF-treated TRPV1 KO mice. Chronic administration of NGF resulted in a significant increase of spinal c-Fos expression in WT mice (P < 0.05 vs KO animals), but not in TRPV1 KO animals. TrkA expression was similar in WT and TRPV1 KO mice. CONCLUSIONS NGF-induced bladder overactivity and noxious input depend on the interaction of NGF with TRPV1. The lack of bladder overactivity in TRPV1 KO mice treated with NGF does not represent loss of TrkA expression. TRPV1 is essential for NGF-driven bladder dysfunction and represents a bottleneck target in bladder pathologies associated with NGF up-regulation.
dc.language.isoeng
dc.rightsrestrictedAccess
dc.subjectCiências da Saúde, Ciências médicas e da saúde
dc.subjectHealth sciences, Medical and Health sciences
dc.titleTransient receptor potential vanilloid 1 mediates nerve growth factor-induced bladder hyperactivity and noxious input
dc.typeArtigo em Revista Científica Internacional
dc.contributor.uportoFaculdade de Ciências da Nutrição e Alimentação
dc.identifier.doi10.1111/j.1464-410X.2012.11187.x
dc.identifier.authenticusP-002-53B
dc.subject.fosCiências médicas e da saúde
dc.subject.fosMedical and Health sciences
Appears in Collections:FCNAUP - Artigo em Revista Científica Internacional

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