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Updated: Mar 13, 2026
Urinary Bladder Distention Evoked Visceromotor Responses as a Model for Bladder Pain in Mice
Published on: April 27, 2014
Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis
Simin Liang1, Jie Li2, Xin Gou2
1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China liangsimin68@163.com.
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.
Insights
Blocking the mammalian target of rapamycin (mTOR) pathway alleviates bladder hyperactivity and pain associated with cystitis. This study identifies mTOR and PI3K signaling as key mechanisms, offering potential new treatments for overactive bladder.
Area of Science:
- Urology
- Pharmacology
- Neuroscience
Background:
- Interstitial cystitis often involves bladder overactivity and pain.
- The mammalian target of rapamycin (mTOR) pathway's role in cystitis is not fully understood.
Purpose of the Study:
- To investigate the effect of blocking mTOR on cystitis-induced bladder hyperactivity and pain.
- To elucidate the mechanisms by which mTOR regulates sensory activity in cystitis.
Main Methods:
- Cyclophosphamide was used to induce cystitis in rats.
- Intrathecal rapamycin was administered to block mTOR.
- Expression levels of mTOR, p-S6K1, p-4E-BP1, and p-PI3K were analyzed.
- Spinal levels of substance P and calcitonin gene-related peptide were measured.
Main Results:
- Cyclophosphamide-induced cystitis amplified mTOR, p-S6K1, p-4E-BP1, and p-PI3K expression.
- Intrathecal rapamycin attenuated bladder hyperactivity and pain.
- Inhibition of the PI3K pathway reduced mTOR activity, bladder hyperactivity, and pain.
- Inhibition of mTOR or PI3K decreased enhanced spinal substance P and calcitonin gene-related peptide.
Conclusions:
- This study reveals mTOR and PI3K signaling pathways are activated in cyclophosphamide-induced bladder hyperactivity and pain.
- Inhibiting these pathways effectively alleviates cystitis-related pain.
- Targeting mTOR and PI3K signaling presents potential therapeutic strategies for overactive bladder and pain in cystitis.
