title: Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China liangsimin68@163.com.
authors: Simin
authors: S
authors: Liang
authors: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Jie
authors: J
authors: Li
authors: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Xin
authors: X
authors: Gou
authors: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Daihui
authors: D
authors: Chen
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D003520:Cyclophosphamide / Q000633:toxicity; D003556:Cystitis / Q000139:chemically induced / Q000150:complications*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy / Q000209:etiology; D007166:Immunosuppressive Agents / Q000633:toxicity; D009025:Morpholines / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000378:metabolism / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D003520:Cyclophosphamide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D015740:Calcitonin Gene-Related Peptide; D020123:Sirolimus
keywords: Cystic pain; bladder activity; cystitis; mTOR; rapamycin