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

Autor: Xin Gou, Daihui Chen, Simin Liang, Jie Li
Rok vydání: 2016
Předmět:
Calcitonin Gene-Related Peptide
Morpholines
Urinary Bladder
Pain
Pharmacology
Contractility
Phosphatidylinositol 3-Kinases
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Ribosomal Protein S6 Kinases
Cystitis
Hypersensitivity
bladder activity
Animals
Medicine
Enzyme Inhibitors
Phosphorylation
Rats
Wistar
Cyclophosphamide
PI3K/AKT/mTOR pathway
Sirolimus
rapamycin
business.industry
Blocking (radio)
Ribosomal Protein S6 Kinases
70-kDa
Interstitial cystitis
medicine.disease
Rats
Disease Models
Animal
Anesthesiology and Pain Medicine
Chromones
030220 oncology & carcinogenesis
mTOR
Bladder Disorder
Molecular Medicine
Female
business
Proto-Oncogene Proteins c-akt
Immunosuppressive Agents
030217 neurology & neurosurgery
Signal Transduction
Research Article
Cystic pain
Zdroj: Molecular Pain
ISSN: 1744-8069
Popis: 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.
Databáze: OpenAIRE
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