Hypothesis / aims of study
Interstitial cystitis/bladder pain syndrome (IC/BPS) significantly impairs patients' quality of life and imposes a substantial economic burden. Currently, treatment options for bladder pain in IC/BPS patients remain limited. Recent studies have reported that the paraventricular nucleus (PVN) in the brain is involved in the formation and modulation of visceral pain [1]. Therefore, establishing a mouse model of chronic bladder pain and investigating associated brain functional alterations are of critical importance for elucidating the central pathogenesis of this disorder and identifying novel therapeutic targets.
Study design, materials and methods
In this study, a chronic bladder pain model was first established using a previously reported protocol [2], wherein cyclophosphamide (75 mg/kg) was administered via intraperitoneal injection on days 1, 4, and 7. Chronic evoked pain behaviors in mice were assessed using Von-Frey filament testing and open-field assays. Subsequently, c-Fos immunofluorescence staining was performed on brain tissues of the chronic bladder pain model mice to evaluate activation patterns in relevant brain regions. Finally, targeted inhibition of specific brain areas was achieved through stereotaxic microinjection, and the analgesic effects were analyzed using Von-Frey filament testing and open-field behavioral assays.
Interpretation of results
Previous studies have extensively reported the involvement of the PVN in the neural transmission of visceral pain. In this study, we demonstrate that mice with chronic bladder pain exhibit characteristic spontaneous and evoked pain behaviors, and these phenotypes can be ameliorated by PVN inhibition. Our findings thus reveal a critical link between chronic bladder pain and heightened neuronal activity in the PVN, providing a theoretical foundation for brain-machine interface (BMI)-based therapeutic strategies targeting chronic bladder pain.