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Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis

BACKGROUND: Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The purposes of this study were to examine (1) the effects of blocking mammalian target of rapamycin (mTOR) on the exaggerated bladder activity and pain evoked by cys...

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Autores principales: Liang, Simin, Li, Jie, Gou, Xin, Chen, Daihui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084610/
https://www.ncbi.nlm.nih.gov/pubmed/27780878
http://dx.doi.org/10.1177/1744806916668868
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author Liang, Simin
Li, Jie
Gou, Xin
Chen, Daihui
author_facet Liang, Simin
Li, Jie
Gou, Xin
Chen, Daihui
author_sort Liang, Simin
collection PubMed
description BACKGROUND: Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The purposes of this study were to examine (1) the effects of blocking mammalian target of rapamycin (mTOR) on the exaggerated bladder activity and pain evoked by cystitis and (2) the underlying mechanisms responsible for the role of mTOR in regulating cystic sensory activity. RESULTS: The expression of p-mTOR, mTOR-mediated phosphorylation of p70 ribosomal S6 protein kinase 1 (p-S6K1), 4 E–binding protein 4 (p-4 E-BP1), as well as phosphatidylinositide 3-kinase (p-PI3K) pathway were amplified in cyclophosphamide rats as compared with control rats. Blocking mTOR by intrathecal infusion of rapamycin attenuated bladder hyperactivity and pain. In addition, blocking PI3K signal pathway attenuated activities of mTOR, which was accompanied with decreasing bladder hyperactivity and pain. Inhibition of either mTOR or PI3K blunted the enhanced spinal substance P and calcitonin gene-related peptide in cyclophosphamide rats. CONCLUSIONS: The data for the first time revealed specific signaling pathways leading to cyclophosphamide-induced bladder hyperactivity and pain, including the activation of mTOR and PI3K. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.
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spelling pubmed-50846102016-11-08 Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis Liang, Simin Li, Jie Gou, Xin Chen, Daihui Mol Pain Research Article BACKGROUND: Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The purposes of this study were to examine (1) the effects of blocking mammalian target of rapamycin (mTOR) on the exaggerated bladder activity and pain evoked by cystitis and (2) the underlying mechanisms responsible for the role of mTOR in regulating cystic sensory activity. RESULTS: The expression of p-mTOR, mTOR-mediated phosphorylation of p70 ribosomal S6 protein kinase 1 (p-S6K1), 4 E–binding protein 4 (p-4 E-BP1), as well as phosphatidylinositide 3-kinase (p-PI3K) pathway were amplified in cyclophosphamide rats as compared with control rats. Blocking mTOR by intrathecal infusion of rapamycin attenuated bladder hyperactivity and pain. In addition, blocking PI3K signal pathway attenuated activities of mTOR, which was accompanied with decreasing bladder hyperactivity and pain. Inhibition of either mTOR or PI3K blunted the enhanced spinal substance P and calcitonin gene-related peptide in cyclophosphamide rats. CONCLUSIONS: The data for the first time revealed specific signaling pathways leading to cyclophosphamide-induced bladder hyperactivity and pain, including the activation of mTOR and PI3K. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis. SAGE Publications 2016-10-25 /pmc/articles/PMC5084610/ /pubmed/27780878 http://dx.doi.org/10.1177/1744806916668868 Text en © The Author(s) 2016 http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Article
Liang, Simin
Li, Jie
Gou, Xin
Chen, Daihui
Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis
title Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis
title_full Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis
title_fullStr Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis
title_full_unstemmed Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis
title_short Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis
title_sort blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084610/
https://www.ncbi.nlm.nih.gov/pubmed/27780878
http://dx.doi.org/10.1177/1744806916668868
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