Advertisement

 

 

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

Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis.
Author Information (click to view)

Liang S, Li J, Gou X, Chen D,


Liang S, Li J, Gou X, Chen D, (click to view)

Liang S, Li J, Gou X, Chen D,

Advertisement

Molecular pain 2016 Oct 2512() pii 1744806916668868
Abstract
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.

Submit a Comment

Your email address will not be published. Required fields are marked *

17 − thirteen =

[ HIDE/SHOW ]