Stress-induced symptom exacerbation: Stress increases voiding frequency, somatic sensitivity, and urinary bladder inflammation when combined with low concentration cyclophosphamide treatment in mice

Symptom exacerbation due to stress is prevalent in many disease states, including functional disorders of the urinary bladder (e.g., overactive (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS)); however, mechanisms underlying effects on micturition reflex function are unclear. In this study we designed and evaluated a stress-induced symptom (SISE) mouse model that demonstrates increased frequency somatic (pelvic hindpaw) sensitivity. Cyclophosphamide (CYP) (35 mg/kg; i.p., every 48 hours for total 4 doses) or 7 days repeated variate (RVS) did not alter sensitivity; both CYP alone RVS significantly (p ≤ 0.01) decreased weight gain serum corticosterone. treatment when combined with (CYP+RVS) corticosterone, sensitivity gain. CYP+RVS exposure mice (2.6-fold) voiding as determined using conscious, open-outlet cystometry. 0.05) baseline, threshold, peak pressures. We also expression NGF, BDNF, CXC chemokines IL-6 alone, cohorts. Although all treatments exposures content, produced largest increase inflammatory mediators examined. These results demonstrated creates change environment but does result until (CYP+RVS). The SISE will be useful develop testable hypotheses addressing where psychological exacerbates symptoms leading identification targets potential treatments.