Chronic Oxytocin Mitigates Stress-Induced Urinary Frequency and Bladder Dysfunction in Female Rats

Psychological stress significantly worsens lower urinary tract symptoms (LUTS), manifesting as increased urinary frequency and bladder hypersensitivity. Current interventions often target symptoms rather than the underlying stress-induced neurobiological changes. Understanding how stress impacts bladder function and identifying mechanisms to modulate central stress pathways is crucial for developing more effective therapies. Oxytocin (OXT), a neuropeptide known for its roles in social bonding and stress regulation, presents a promising candidate for modulating these stress-related pathways and potentially alleviating LUTS. This study explores OXT's impact on stress-induced bladder dysfunction and central stress pathways.

Female Sprague–Dawley rats (n = 14 per group, total n=42) were divided into control, stress, or stress/OXT groups. The stress groups underwent repeated variable stress (RVS) for one week. The OXT group received chronic oxytocin administration (specific dose not detailed in abstract) alongside RVS. Researchers evaluated mechanical sensitivity, cystometric parameters (e.g., intercontraction intervals), plasma catecholamines and cortisol levels, bladder histology, paraventricular nucleus (PVN) c-Fos expression, and gene expression in bladder and brain regions using techniques like qPCR.

Repeated variable stress (RVS) significantly induced mechanical hypersensitivity and shortened intercontraction intervals. Stressed rats also exhibited increased bladder weight and elevated plasma levels of adrenaline, dopamine, and cortisol. Histological analysis revealed bladder epithelial thickening and submucosal nerve hyperplasia, alongside upregulation of EP3 and ENaC gene expression. Central nervous system changes included a significant increase in PVN activation, as evidenced by c-Fos expression, and upregulated ChAT, CRF, and TH expression in the brainstem. > Chronic OXT treatment effectively normalized intercontraction intervals, restoring them to control levels. Furthermore, OXT significantly reduced elevated catecholamine and cortisol levels, attenuated PVN c-Fos activation, and increased OXTR and GAD expression in the hypothalamus and thalamus. While IL-6 expression was unchanged by stress, OXT treatment led to its decrease. These findings suggest OXT primarily modulates central stress pathways, with limited direct peripheral anti-inflammatory effects.