Voluntary Wheel Running Can Improve Increased Urogenital Sensitivity and Function Resulting from Neonatal Maternal Separation in Male Mice

A 01 VOLUNTARY WHEEL RUNNING CAN IMPROVE INCREASED UROGENITAL SENSITIVITY AND FUNCTION RESULTING FROM NEONATAL MATERNAL SEPARATION IN MALE MICE Isabella M. Fuentes, Angela N. Pierce, Olivia C. Eller-Smith, Julie A. Christianson Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) shares many symptoms with interstitial cystitis/painful bladder syndrome (IC/PBS), and the two are commonly codiagnosed. Almost half of those diagnosed with these functional pain disorders also suffer from mood disorders, particularly depression and/or anxiety. Additionally, many of these patients have a reported history of early life stress. Experience of such stress has been associated with dysfunctional stress response in adulthood, attributed to altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Comorbidity of these disorders and unknown etiology has complicated or hindered the development of effective treatment options. However, regular exercise has been shown to improve pain perception and attenuate many symptoms ascribed to irregular HPA axis function in clinical and preclinical studies. Here we investigated the therapeutic potential of voluntary wheel running to mitigate perigenital hypersensitivity and mood behaviors associated with a male mouse model of neonatal maternal separation (NMS), as well as molecular changes observed. Mice were born in house and were either unhandled, aside from normal husbandry procedures, or subjected to NMS from postnatal day 1 to 21. Mice were then placed in new cages with unlimited running wheel access beginning at 4 (-Eex) or 8 (Lex) weeks of age. Sedentary controls (-Esed/-Lsed) remained in home cages. NMSexposed mice displayed significant perigenital mechanical sensitivity, increased micturition patterning, and increased mast cell degranulation in urogenital tissues. These alterations were prevented or reversed by voluntary wheel running. Differences in concentrations of serum corticosterone and central gene expression changes suggest improper functioning of the HPA axis. However, our data does not indicate NMS-induced anhedonicor anxiety-like behaviors. Conclusion: Together, these data suggest NMS in male mice can be a useful model for comorbid CP/CPPS and IC/PBS, and voluntary exercise may be a viable therapeutic option to improve symptom severity.